US originators slam EU on SPC waiver proposal · Richter'sEsmya Zydus'Moraiyaplant 7 completesFDAaudit Upsher-SmithassistsinSawaisalessurge 7 ... on its watchlist in its upcoming

23 February 2018

US originators slam EUon SPC waiver proposal

COMPANY NEWS 2Cutting research cost 2bolsters Towa profits

Alkem's sales climb by 17.4% on Indian rise2

Sandoz stays schtum on US 3sell-off rumour

UK drops probe into Concordia eye drops 3

Site expansions help boost Granules' sales 4

Cambrex keeps focus 4on active ingredients

Sun is still suffering as US sales plummet 5

Glenmark eyes study for Xolair next year 5

EMA takes action to bar 6Richter's Esmya

Zydus' Moraiya plant 7completes FDA audit

Upsher-Smith assists in Sawai sales surge 7

MARKET NEWS 8CREATES act in US may still pass in 2018 8

FDA intends to learn before 8product guides

US companies should steer story on pricing 9

Structured reviews will accelerate ANDAs 9

Second filers in US to 10trigger 180-day term

EU updates guidance on 10falsified medicines

France and UK take UPC protocol action12

PRODUCT NEWS 13Sandoz' US Humira petitions 13are refused

Celltrion's Herzuma receives Europe nod13

Amneal gets backing on 14US Nasonex rival

Biocad has plans to ship Remicade rival 15

Canada denies chance 15to choose on damages

REGULARSEvents – Our regular listing 12

Price Watch UK – Our regular listing 13

People – Saneca selects Král to 16replace chief Sheehan

Issue No.342

Aproposed exemption allowing generics firms to manufacture in Europe for export orstockpiling during the term of a supplementary protection certificate (SPC) “would

have significant detrimental economic impact on research-based companies both in Europeand around the globe” and should lead the US Trade Representative (USTR) to place theEuropean Union (EU) on its watchlist in its upcoming 2018 ‘Special 301’ report onintellectual property (IP), according to US brand industry association PhRMA. Off-patentindustry association Medicines for Europe has long called for such a waiver.

“PhRMA is very concerned about proposals... that may weaken the scope of the exclusiverights conferred under an SPC,” the brand body told the USTR. This had been “exacerbatedby the public consultation launched in October” (Generics bulletin, 20 October 2017, page 1).PhRMA said the belief that a waiver could level the global playing field for EU-based genericsmanufacturers “appears to be based on a single study that has been debunked”.

In particular, PhRMA said, preventing potential abuses of the waiver – such as illegaldiversions of medicines within Europe or to other markets where patents had not expired –“would be very difficult”. “Safeguards that would be necessary include inspecting, regulatingand tracking every lot to ensure it is exported as intended,” PhRMA claimed, suggesting that“in the end, it may well be impossible to limit the exemption to its intended purpose”.

Warning that an export manufacturing waiver “will almost certainly be copied by othereconomies, possibly in an exaggerated form that is even more damaging to biopharmaceuticalinnovators in the US, Europe and elsewhere”, PhRMA suggested that “if a leading developedeconomy like Europe bends the rules, others are sure to break them”.

PhRMA said the US government should “seek assurances that ongoing reviews will notresult in measures to weaken IP protections”. With a wider review of EU incentives also beingconducted by the European Commission, “PhRMA and its member companies are very concernedthat it could result in proposals to reopen critical parts of Europe’s IP framework and potentiallyweaken existing incentive mechanisms that support biopharmaceutical innovation”. G

Former Teva and Actavis generics chief Siggi Olafsson has been appointed as chief executiveofficer of Hikma. He succeeds chairman and chief executive Said Darwazah, who will continue

to chair Hikma’s board of directors, taking on the title of executive chairman.As chief, Hikma noted, Olafsson would be responsible for the “effective development and

execution of Hikma’s corporate strategy, focusing on opportunities to accelerate growth of theglobal business”. Meanwhile, Olafsson has also been lined up to take a seat on Hikma’s board,subject to election at Hikma’s 2018 annual general meeting in May.

Robert Pickering, Hikma’s senior independent non-executive director, said Olafsson wasjoining at a “pivotal time for Hikma, as we embark on our next chapter”. Failure to land USapproval for generic Advair (fluticasone/salmeterol) in May (Generics bulletin, 19 May 2017,page 1) and “greater than expected price and volume erosion” in the US led Hikma to cut itsnon-injectables Generics unit’s full-year sales forecast three times last year – from US$800million to US$600 million – while the business’ core operating margin is anticipated to be in thelow single-digits (Generics bulletin, 17 November 2017, page 4). Hikma also recently broughtin Daniel Motto as vice-president of US injectables, stating “the dynamics of our industry are changingfast”. Hikma said it was confident that Olafsson and Darwazah, working together, “will significantlyenhance our ability to execute our strategy and deliver long-term sustainable growth”. G

Olafsson appointed Hikma chief

2 GENERICS bulletin 23 February 2018

COMPANY NEWS

Register online: www.europlx.com

The Original since 1995.Often copied. Never equaled.

Seeking and offering business opportunities in patented and generic (incl.biosimilars), prescription and OTC drugs, medical devices, and nutraceuticals -development, licensing, marketing, promotion, and distribution…

Each euroPLX Conference’s actual collaboration interests are summarised anddisplayed onwww.europlx.com as an hourly updated Dynamic PartneringFocus, as soon as sufficient data are submitted by registrants.

[email protected]. ++49 (6221) 426296-0

Insanely EffectivePharma PartneringeuroPLX is the world’s most often heldpartnering conference for the pharmaand biopharma industries.Because of results delivered. Year-round.

Join the 67th International PartneringConference for Pharma Business Development

euroPLX 67 Noordwijk (The Netherlands)June 11 + 12, 2018, Grand Hotel Huis ter Duin, Noordwijk

Reducing research and development (R&D) costs by 13.9% to ¥5.91billion (US$55.6 million) helped to push up Towa’s operating

profit by more than two-thirds – 67.2% – to ¥9.21 billion in the firstnine months of the Japanese firm’s financial year ending 31 March2018, on sales that improved by just over a tenth to ¥70.4 billion.

“Sales increased with good results from recently-launched products,”Towa commented, while operating profit had improved “mainly dueto a decrease in R&D costs”.

Noting that its turnover for the nine-month period was “in linewith the plan” – constituting 74.9% of the ¥94.0 billion sales total thatTowa expects to report for its full financial year – the firm observedthat its nine-month operating profit had already exceeded the full-yeartotal of ¥8.60 billion that the company had previously forecast. Arevised financial forecast now anticipates that Towa’s full-year operatingprofit will rise by 71.8% to ¥11.8 billion, giving it an operating margin3.5 points higher than originally anticipated at 12.6%.

Towa reduced the proportion of its turnover that was achievedthrough sales agents “due to opening new offices, and increasedheadquarters transactions”, with the proportion of sales through agentsfalling from 34.2% in the prior-year period to 27.4%. “Deals withwholesalers started from this fiscal year,” the firm observed, withwholesalers accounting for 11.6% of Towa’s sales. Just over half ofturnover – 56.4% – came from direct sales. G

NINE-MONTH RESULTS

Cutting research costbolsters Towa profits

Domestic sales rising by 22.0% helped India’s Alkem Laboratoriesachieve growth of 17.4% to Rs17.4 billion (US$272 million) in its

financial third quarter ended 31 December 2017 (see Figure 1). Alkem“maintained leading positions” in India for anti-infectives, gastrointestinalproducts, analgesics and vitamins, minerals and supplements.

Alkem’s pre-tax profit climbed by 30.1% to Rs3.32 billion withRs927 million spent on research and development. “We have not onlyachieved robust revenue growth, but have also complemented it withimprovement in our profit margins,” noted managing directorSandeep Singh. “We are continuously investing in our capabilities,people and infrastructure to build newer avenues of growth.” G

THIRD-QUARTER RESULTS

Alkem’s sales climb by17.4% on Indian rise

Figure 1: Breakdown by region of Alkem’s sales in its financial third quarter ended31 December 2017 (Source – Alkem)

India 12,567 +22.0 73

US 3,592 +6.1 21Others 1,068 +13.7 6International 4,660 +7.8 27

Other 178 – –

Alkem 17,405 +17.4 100

Region Third-quarter sales Change Proportion(Rs millions) (%) of total (%)

3GENERICS bulletin23 February 2018

COMPANY NEWS

The UK’s Competition and Market Authority (CMA) investigationinto Concordia International’s “suspected unfair pricing” practices

will now focus “exclusively” on the Canada-based firm’s liothyroninetablets, after the watchdog closed its investigation into Concordia’spricing for fusidic acid eye drops.

In late October 2016, the CMA announced it had officially openedan investigation relating to the “charging of excessive prices in thesupply of certain pharmaceutical products, including to the NationalHealth Service (NHS)” (Generics bulletin, 4 November 2016, page10). Although the watchdog did not identify firms under scrutiny atthe time, Concordia revealed it was part of the inquiry.

The CMA had also not previously revealed fusidic acid eye dropswere part of its investigation. It noted a decision had been made to“focus exclusively on liothyronine and de-prioritise investigation intoanother product”. However, in acknowledging the CMA’s October2016 investigation, Concordia underlined “fusidic acid eye drops wasone of those products”. “The CMA has notified the company that itis closing its investigation related to fusidic acid,” Concordia said.

In response to the decision, Concordia said it had been “consistentin its belief that competition law in the UK has not been infringed,including in relation to the pricing of our medicines”. “We haveengaged in open and transparent communication with the CMA onthese matters, and this dialogue has resulted in the CMA closing itsinvestigation into fusidic acid eye drops,” Concordia added.

As part of the CMA’s investigation, the watchdog provisionallyfound, in November last year, that Concordia “abused its dominantposition to overcharge the NHS by millions” for liothyronine, in breachof UK and European Union (EU) competition law (Generics bulletin,24 November 2017, page 7). The CMA said that in 2016, the NHSspent more than £34 million (US$47.7 million) on the drug, up fromaround £0.6 million in 2006, with Concordia until 2017 “the onlysupplier” and enjoying production costs that remained “broadly stable”.

In response to the accusations, Concordia insisted competition lawhad not been infringed, and said “the pricing of liothyronine has beenconducted openly and transparently with the Department of Health inthe UK over a period of 10 years” (Generics bulletin, 1 December2017, page 12). Concordia pledged to “work constructively with theCMA on the remaining open matters to seek joint resolution”. G

INVESTIGATIONS

UK drops probe intoConcordia eye drops

Indoco Remedies’ ‘Plant I’ solid-dosage facility in Goa, India, hasreceived eight ‘Form 483’ observations following an inspection by

the US Food and Drug Administration (FDA). “All the observations arecorrectable, and the company is in the process of preparing its response,”Indoco commented, noting that exports from the solid-dosage plant“constitute less than 10% of the company’s total export sales”.

Separately, Indoco’s ‘Plant III’ manufacturing facility for non-sterile products – also located in Goa – has been granted a Europeangood manufacturing practice (GMP) certification from Hungary’sregulatory authority. The company said the certification would “enableIndoco to continue to export medicinal products to all Europeancountries”, and would support export sales to Canada, Australia,New Zealand, and the “rest of the emerging territories”. G

MANUFACTURING

Indoco gets eight observations

Sandoz has declined to comment on a Reuters report suggestingthat parent group Novartis is “preparing to auction its US generic

pill business” amid steep price erosion.A Sandoz spokesperson referred to the generics division’s previous

statement that “as we continue to reshape our business in the US towardsa more specialised and differentiated portfolio, we are continuouslyevolving our product portfolio for long-term stability and growth”.

“We want to ensure that we focus our investments in the US instrategic areas that will drive growth for the company going forwardand improve access to important therapy options for patients. As partof this ongoing process we are also looking at potentially divestingor discontinuing certain non-core or negative margin products in theUS,” he said, noting that the division had already divested a numberof low- and negative-margin products in the US over the past 12 monthsin deals that were not financially material.

Sandoz recently sold a portfolio of 25 approved abbreviated newdrug applications (ANDAs), one tentatively approved ANDA andthree more that are pending US approval, to Casi Pharmaceuticalsfor US$18 million (Generics bulletin, 2 February 2018, page 4).

“The US is a very important market for Sandoz and will continueto be so in the future. We are confident that our focus on value-addedproducts can drive sustainable profitable growth in the US over thelong term,” the spokesperson stressed.

Following a recent discussion with Novartis’ chief financialofficer, Harry Kirsch, investment bank Jefferies said Novartis was“exploring options for [Sandoz’] US orals unit, but would not considera fire sale given it is still profitable and highly cash-generative”.

Oral solids ‘facing challenges’Presenting Novartis’ 2017 annual results, newly-appointed group

chief executive officer Vas Narasimhan said: “We have very strongglobal Sandoz business, and it is growing well outside of the US, aswell as [having] the leading biosimilars portfolio. But we are facingchallenges given the oral solids industry-wide pricing pressure in theUS. We will plan to continue to reshape our US business with a focuson more complex products, and that will include looking at how to bestshape that portfolio for us to be successful in the future.” He describedSandoz’ US$1.5 billion US oral solids operation as “a discrete business”.

As it looks to streamline its US manufacturing base, Sandoz hasjust announced 65 redundancies at its solid-dose site in Broomfield,Colorado, that is slated for closure under plans announced last year(Generics bulletin, 3 November 2017, page 4).

With total US sales 12% lower at US$3.28 billion on a 14% slidein Retail Generics turnover “due to increased industry-wide pricingpressure and continued customer consolidation”, Sandoz’ global turnoverfell by 1% as reported, and by 2% on a constant-currency basis, toUS$10.1 billion last year as eight percentage points of price erosionmore than cancelled out six points of volume growth. G

BUSINESS STRATEGY

Sandoz stays schtumon US sell-off rumour

BERKSHIRE HATHAWAY – billionaire Warren Buffet’s investmentcompany – holds almost 18.9 million sponsored Americandepositary receipts (ADRs) in Teva valued at nearly US$358 million,according to a recent filing with the US Securities and ExchangeCommission (SEC). G

IN BRIEF


COMPANY NEWS

[email protected]

Issue 342 l 23 February 2018

Director of Subscriptions: Val Davis Group Sales Manager: Rob Coulson

Awards Manager: Natalie Cornwell Production Controller:Debi Robinson

Production Editor: Jenna Meredith Managing Director: Philip Jarvis

l General enquiries: [email protected] l Subscription enquiries: [email protected]

l Editorial enquiries: [email protected] l Advertising enquiries: [email protected]

Editor: Aidan Fry

[email protected]

Deputy Editor: David Wallace

[email protected]

Assistant Editor: Dean Rudge

[email protected]

Business Reporter: Grace Montgomery

Terms & Conditions: See www.generics-bulletin.com/subscribe.While due care has been taken to ensure the accuracy of information contained in this publication,the publisher makes no claim that it is free of error and disclaims any liability whatsoever for anydecisions or actions taken as a result of its contents.

Published by OTC Publications Ltd, 4 Poplar Road, Dorridge, Solihull B93 8DB, UK.Tel: +44 (0) 1564 777550 Fax: +44 (0) 1564 777524Company registered in England No 02765878.© OTC Publications Ltd. All rights reserved.Generics bulletin® is registered as a trademark in the European Community.Printed by Warwick Printing Company Ltd. ISSN 1742-0784

Developing and launching new generic active pharmaceuticalingredients (APIs) remains a “key growth driver” moving forward

for bulk-drugs producer Cambrex, according to the US-based firm’spresident and chief executive officer, Steven Klosk.

“We currently have 13 generic APIs and one controlled substancein later stages of development,” Klosk revealed. “We have severalmore generic APIs in earlier stages of technical and economicevaluation that would be moved into development if they meet criteria.”

Sales of Generic APIs increased by a tenth to US$106 million in2017, excluding the impact of foreign currency effects, Klosk revealedas Cambrex reported its full-year financial results. This amounted toaround a fifth of total sales that climbed by 9% to US$534 million.

“For 2018, we expect net revenue growth from the Generic APIsto be about flat, with underlying growth in the low-to-mid single-digitrange being offset by the impact of certain of our customers discontinuingsales of a few products in the US market,” Klosk forecasted. The bulkof Cambrex’ sales – US$353 million – stemmed from sales of itsInnovator APIs, for which Gilead Sciences is a key customer.

Meanwhile, Klosk reiterated that Cambrex expected to see revenuesfrom its initiatives to develop finished-dose generic formulations forthe US market “beginning in late 2019 to early 2020”.

Having filed three abbreviated new drug applications (ANDAs)with the US Food and Drug Administration (FDA) in 2017, Cambrex,Klosk said, “continues to develop a number of additional genericdrug products and anticipates filing a few more ANDAs during 2018”.The three filed ANDAs all had target dates under the Generic DrugUser Fee Amendments (GDUFA), he revealed.

“We are working with formulation development and manufacturingpartners and expect to work with generic marketing partners to sellthese products when they are approved,” Klosk revealed. Cambrex’focus was “primarily on niche products, similar to our strategy ingeneric APIs”. “So in that regard, they tend to be on the smaller side,certainly not blockbuster generic APIs. This is a measured initiativethat we have,” Klosk added. “We’re going to see how we do.”

Group sales of US$534 million produced an operating profit thatincreased by 11.2% to US$143 million, moving Cambrex’ operatingmargin up by 0.5 percentage points to 26.7%. “Strong performanceat our manufacturing facilities resulted in higher profit margins versuslast year,” Klosk insisted. G

BUSINESS STRATEGY/ANNUAL RESULTS

Cambrex keeps focuson active ingredients

Granules India says that capacity expansion at two of its local facilitiesenabled the firm to boost its group turnover by 14% to Rs4.11

billion (US$63.7 million) in its financial third quarter ended 31 December2017. During the quarter, Granules started commercial productionof additional active pharmaceutical ingredients (API) capacity at itsBonthapally facility – including metformin and paracetamol – andalso expanded its intermediates plant in Gagillapur.

“We believe the enhanced facility shall not only enable us tode-bottleneck capacity constraints, but also help steadily increasebusiness development,” commented chairman and managing directorKrishna Prasad Chigurupati, highlighting a promising start to production.API sales advanced by over a fifth, while intermediates turnover roseby 17%, although gross profit margin declined “due to increasedprice in some of our key raw materials”.

After an inspection by the US Food and Drug Administration(FDA) of its US facility in Virginia in December last year, Granulesreceived one ‘Form 483’ observation. “We have submitted our responsewithin the stipulated time, and expect a favourable establishmentinspection report (EIR),” the firm stated. Noting it had filed fiveabbreviated new drug applications (ANDAs) in the nine-month period,Granules said the company was “optimistic we will achieve the targetof 10 ANDA filings… during this year”, with the remaining fiveexpected to be filed “in this current quarter”. Six ANDAs will comefrom the Virginia facility and four from Hyderabad, India, the firmdivulged, and “there will be complex filings”.

Acknowledging that its profile would change with the higherproportion of complex products by 2022-2023, Granules said the firmwould receive approvals for such products in 2019, with some beingsecured in 2018, including one imminent approval.

Responding to an investor query about Granules’ 2019 financialyear representing the company’s “new era”, Chigurupati admitted thatthis had been postponed by “a few quarters”. Stating that the firmwould “see new products hitting the market”, he revealed one first-to-market product would be introduced “in the next one or two months”.“There is only one brand, and we will be the first generic to hit themarket,” Chigurupati claimed. “That itself is a big change for Granulesfrom the way we were working before.” He added this was “a changein the operational style of Granules, from core high-volume moleculesgoing into really low-volume, but high-value products”. G


Site expansions helpboost Granules’ sales


COMPANY NEWS

Pricing pressure in the US, lower sales of generic imatinib andolmesartan authorised generics, and delayed approvals for new

products from its key Halol manufacturing facility caused Sun Pharma’sUS turnover to plunge by 37.9% to Rs21.2 billion (US$332 million)in the firm’s financial third quarter ended 31 December 2017.

Group turnover declined by 14.1% to Rs66.0 billion, entirely dueto the drop in US sales. Managing director Dilip Shanghvi said that“despite a challenging US generic pricing environment”, the company’sthird-quarter performance “reflects a gradual improvement inprofitability over the first half of this year”.

The Indian firm’s domestic turnover advanced by 5.9% to Rs20.9billion, although Sun admitted that this growth was “not strictlycomparable to year-on-year periods” due to the introduction of the

local goods and services tax (GST). Emerging Markets sales rose by5.3% to Rs12.2 billion, “boosted by the consolidation of the Biosintezacquisition in Russia”. Meanwhile, sales from 14 brands in Japanacquired from Novartis in 2016 helped to lift Sun’s Rest of Worldturnover by 2.2% to Rs7.77 billion (see Figure 1).

Research and development spending – which slid by 22.8% to Rs4.73billion – included “investments on account of funding the clinicaldevelopment of our global specialty pipeline”. “During the quarter,we took another step forward in enhancing our specialty business,by reporting acceptance of the new drug application (NDA) filing forOTX-101 (cyclosporine) 0.09% ophthalmic solution by the US Foodand Drug Administration (FDA),” Shanghvi stated. “We want todevelop an attractive product pipeline for developing a globalophthalmology and dermatology business, so those are the kind ofproducts and companies that we are looking at.”

Having filed four abbreviated new drug applications (ANDAs)and obtained five approvals with the FDA during the quarter, Sunnoted it had 126 ANDAs pending approval. Shanghvi pointed out thatthe number of pending ANDAs had “reduced slightly” after the firm had“dropped certain non-viable products”, although he did not disclosefurther details. And when quizzed by investors on whether the FDAwould be re-inspecting Halol imminently, Shanghvi declined to comment.

Separately, Sun has confirmed media reports that a fire broke outat its Indian intermediate and active pharmaceutical ingredient (API)manufacturing plant in Ankleshwar, Gujarat, on 4 February. Statingthat there were “no injuries” and “no direct loss of production”, thefirm said “a detailed investigation is under progress”. Gn [email protected]


Sun is still sufferingas US sales plummet

Figure 1: Breakdown by region and business of Sun Pharma’s net sales in itsfinancial third quarter ended 31 December 2017 (Source – Sun Pharma)

US 21,242 -37.9 32India 20,850 +5.9 32Emerging Markets 12,212 +5.3 19Rest of World 7,766 +2.2 12Formulations 62,070 -15.1 94

Bulk Drugs 3,698 +1.1 6

Other 215 +144.5 –

Sun Pharma 65,982 -14.1 100

Third-quarter sales Change Proportion(Rs millions) (%) of total (%)

Glenmark anticipates beginning Phase III clinical trials for itsproposed biosimilar of Genentech and Novartis’ Xolair (omalizumab)

in the fourth quarter of its next financial year ending 31 March 2019,assuming a favourable outcome for the firm’s ongoing Phase I study.Enrolment completed this month, noted Glenmark, with 168 patientsrandomised and dosed. Top-line results are expected by July 2018.

The GBR 310 omalizumab candidate is one of several assets thatGlenmark is developing in line with its strategic push towards specialtyproducts and original brands. Currently, Glenmark is spending around8% of its sales on research and development (R&D) for specialty andinnovative assets, out of an approximate 12% total R&D spend, with“most” of that figure going on the Xolair biosimilar in recent quarters,according to chairman and managing director Glenn Saldanha.

In the Indian firm’s 2019 financial year, as part of its Specialtypush, Glenmark anticipates filing with the US Food and DrugAdministration (FDA) generic applications for NuvaRing (ethinylestradiol/etonogestrel), Concerta (methylphenidate), and GSP-103, whichSaldanha revealed to be generic Flovent (fluticasone propionate).

Meanwhile, Saldanha underlined plans to file a 505(b)(2) hybridnew drug application (NDA) for the Ryaltris (mometasone/olopatadine)nasal spray combination with the FDA “in the next two-to-three months”.“We are still working on our launch strategy,” Saldanha noted. “Wecan’t give too much visibility, other than the fact we are anticipatinga launch in the first quarter of [financial year ending March 2020].”

Glenmark’s ‘USA Formulations’ sales tumbled by two-fifthsto Rs7.36 billion (US$114 million) in its financial third quarter, asthe business normalised following Glenmark’s launch of the firstgeneric of Merck & Co’s Zetia (ezetimibe), in partnership with Endo’sPar, in December 2016. Price erosion also affected sales.

Saldanha said a forecast of 13% price erosion in the US “for atleast the next five quarters” was due to anticipated competition ongeneric Bactroban (mupirocin) topical cream “coming through overthe next six-odd months”. Glenmark currently holds the only genericapproval. Meanwhile, Saldanha revealed the firm is “looking muchmore closely” at backward integrating some of its products in the US.

The sales slump for Glenmark USA Formulations ultimately ledto group turnover sliding by 13.1% to Rs22.0 billion, offsetting solidgrowth in India and African, Asian and Commonwealth of IndependentState (CIS) markets as well as Europe (see Figure 1). Consolidatedearnings before interest, tax, depreciation and amortisation (EBITDA)tumbled by almost three-fifths to Rs3.23 billion. Gn [email protected]

BUSINESS STRATEGY/THIRD-QUARTER RESULTS

Glenmark eyes studyfor Xolair next year

US 7,359 -40.2 33India 5,785 +11.9 26Africa/Asia/CIS 3,221 +28.3 15Europe 2,248 +14.8 18Latin America 898 -5.2 4API 2,316 +20.6 11Licensing/other 209 -61.1 1

Glenmark 22,037 -13.1 100

Figure 1: Breakdown of Glenmark Pharmaceuticals’ sales in its financial thirdquarter ended 31 December 2017 (Source – Glenmark)

Third-quarter sales Change Proportion(Rs millions) (%) of total (%)


COMPANY NEWS

Gedeon Richter has vowed to work with the European MedicinesAgency’s (EMA’s) Pharmacovigilance Risk Assessment Committee

(PRAC), and insisted it “takes patient safety seriously”, after thecommittee advised that no new patients start taking the Esmya (ulipristalacetate) women’s healthcare brand until it completes a safety evaluation.

The review of the benefits and risks with the treatment for uterinefibroids – which Richter licenses from Allergan in Europe – wasinitiated in December last year, following reports of serious liver injury.Richter says it will “provide the necessary information to allow [PRAC]to complete a fair assessment in a timely manner”.

PRAC also recommended regular liver monitoring, and suggestedthat no patients who have completed a course of treatment shouldstart another one “for the time being”.

Pointing out that a final decision on these temporary safety measures“depends on the conclusion of the review of Esmya, which is expectedto be completed before end of May 2018”, the Hungarian firm said itcontinued to believe that “all the available data for Esmya support afavourable benefit-risk profile” for the uterine fibroids treatment.

Richter’s global sales of Esmya climbed by more than a third –34.8% – to C93.0 million (US$116 million) in 2017, following stronggrowth in European Union 15 (EU15) markets. This amounted to afifth of total Women’s Healthcare turnover that rose by 17.3% to C469million, which was also bolstered by increased sales of the Bemfola(follitropin alfa) biosimilar, from C10.6 million to C34.6 million.

As Figure 1 shows, Richter’s total Pharmaceutical turnoverclimbed by 13.5% to C1.18 billion, on the back of growth in Russiaand the Commonwealth of Independent States (CIS). Russian salesincreased by a fifth to C310 million, achieved by an “improvingproduct mix, particularly a higher share of the Women’s Healthcarefranchise”, as well as “certain, limited price increases”.

Other financial highlights included sales in the US jumping byjust under half to C88.8 million, “mainly due” to royalty income fromthe Vraylar (cariprazine) treatment of bipolar I disorder that wasco-developed with and marketed by Allergan.

The Pharmaceutical segment’s operating profit climbed by morethan a fifth – 21.7% – to C216 million, Richter noted, moving up thebusiness’ operating margin by 1.3 percentage points to 18.3%. Gn [email protected]

BUSINESS STRATEGY

EMA takes action tobar Richter’s Esmya

Figure 1: Breakdown of Gedeon Richter’s sales in 2017 (Source – Gedeon Richter)

European Union* 406.5 +10.5 28Russia/CIS 417.4 +16.5 29Hungary 114.5 +2.0 8US 88.8 +47.0 6China 77.6 +11.8 5Latin America 19.9 +6.4 1Rest of World 55.0 +4.6 4Pharmaceutical 1,179.7 +13.5 82

Wholesale & Retail 286.0 +19.6 20

Elimination/Other -28.9 – -2

Gedeon Richter 1,436.8 +14.8 100

* excluding Hungary

Annual sales Change Proportion(C millions) (%) of total (%)

JB CHEMICALS & PHARMACEUTICALS said the Indian company’sdecision “to create additional divisions in its domestic formulationsbusiness, to support newer products and increase feet on the street”was “showing good results”, as the firm reported group turnoverthat rose by over a tenth to Rs2.98 billion (US$46.2 million) in itsfinancial third quarter ended 31 December 2017. The firm’s domesticformulations sales increased by 13.8% to Rs1.36 billion. Formulationsexports in Russia and the Commonwealth of Independent States(CIS) and the rest of world advanced by 5.22% to Rs193 millionand 7.16% to Rs937 million respectively. Active pharmaceuticalingredient (API) turnover inched up by 2.44% to Rs155 million.Last year, JB added around 630 staff to “expand the size of itsexisting domestic formulations” (Generics bulletin, 9 June 2017,page 7), and plans to add a further 250 staff from April 2018.

COSMECCA KOREA has received a warning letter from the USFood and Drug Administration (FDA) concerning finished-dosageforms at its manufacturing facility in Chungcheongbuk-do, Korea,following an inspection by the agency in September 2017. The FDAobserved “multiple examples of falsifying laboratory records”, andfound that laboratory equipment used to generate analytical datafor release purposes lacked restricted access. OTC drugs producerCosmecca was placed on import alert by the agency last month.

AUROBINDO has revealed that its new US distribution centrein East Windsor, New Jersey, “is now operational”. “While we aredoing everything necessary to transition shipping operationssmoothly,” the Indian company stated, “there may be instances ofprocessing delays during this time.”

OLAINFARM’S Belarusian herbals specialist NPK Biotest hasreceived a local good manufacturing practice (GMP) certificate,which allows the “packing of five Olainfarm products for the Belarusmarket within this year”. NPK has also become the distributor ofOlainfarm’s elastic medical product daughter company, TonusElast, in Belarus.

ONCOBIOLOGICS plans in 2018 to “organically generatefunding for our biosimilar development programs, in addition toour ongoing efforts to secure additional development partners”. TheUS-based biosimilars developer late last year closed a US$25.0million private share placement with GMS Tenshi Holdings, toadvance its product pipeline (Generics bulletin, 17 November 2017,page 6). Oncobiologics is aiming to move its ONS-3010 adalimumaband ONS-1045 bevacizumab candidates into Phase III clinical trials.Furthermore, the company is preparing for clinical development itsONS-4010 rival to Amgen’s Prolia/Xgeva (denosumab), and ONS-3040,its alternative to Janssen’s Stelara (ustekinumab). “We have alsobegun work on ONS-5010, an innovative drug product candidate,”Oncobiologics divulged. Separately, the firm’s request to transfer itslisting from the Nasdaq global market to the Nasdaq capital markethas been granted, “pursuant to an extension through 15 May 2018to evidence compliance with all applicable requirements for continuedlisting on Nasdaq, including the applicable US$35 million marketcapitalisation requirement”.

MALLINCKRODT has completed its US$1.2 billion acquisition ofSucampo Pharmaceuticals – including its commercial anddevelopment assets such as the Amitiza (lubiprostone) treatmentfor chronic idiopathic constipation – after entering into an agreementwith the firm in December 2017. Mallinckrodt said that Sucampowould bring “near-term net sales and earnings accretion, whilebolstering our pipeline”. G

IN BRIEF


COMPANY NEWS

Afour-month sales contribution from the Upsher-Smith genericsbusiness in the US has helped to boost Sawai’s turnover by 15%

for the first nine months of its financial year ending 31 March 2018,according to the latest figures published by the Japanese firm.

“With the Japanese generics market as a whole growing at aslower pace, and sales of contract manufacturing down from the prioryear, sales in Japan grew by just 1.6%,” Sawai pointed out, taking itsdomestic sales to ¥103 billion (US$968 million) for the nine-monthperiod. However, “overall sales grew by 15.0% thanks to the inclusionof the June to September sales of Upsher-Smith Laboratories” followingSawai’s US$1.05 billion takeover (Generics bulletin, 9 June 2017,page 3), with North American turnover of ¥13.5 billion helping tolift Sawai’s total to ¥116 billion.

Just over two-fifths of these North American sales came fromcardiovascular drugs, Sawai revealed, while central nervous systemtreatments accounted for another 39% (see Figure 1).

In Japan, Sawai’s leading therapeutic category in terms of volumeswas also cardiovascular drugs, which made up 28.1% of the firm’sdomestic sales in unit terms. Gastrointestinal medicines accounted foranother 22.9%, while central nervous system drugs were responsiblefor 12.4% of sales volumes. “Cardiovascular and central nervoussystem drugs have steadily increased,” Sawai observed, with volumegrowth of 7.8% and 5.6% respectively. By value, the two categoriesincreased their respective sales by 8.8% and 8.3%.

During the nine-month period, Sawai saw its local sales throughwholesalers increase by 8.9% to ¥63.0 billion, while turnover throughagencies saw a less pronounced rise of 1.1% to ¥34.3 billion. Marketingalliances and other channels made up the remainder.

As reported, Sawai’s operating profit grew by just 6.7% to ¥19.1billion. However, when costs of ¥1.4 billion relating to the Upsher-Smith acquisition were excluded from the comparison, the growthfigure was more closely in line with that of Sawai’s total turnover,translating to operating profit growth of 14.5% to ¥20.5 billion.

Full-year sales were expected to reach ¥169 billion, Sawai stated –comprising ¥137 billion in Japan and ¥31.7 billion in North America –with expected operating profit of ¥23.7 billion. With a total of fourlaunches planned in North America for Sawai’s current financial yearending 31 March 2018, the firm indicated that seven or eight wereexpected in the following financial year. Gn [email protected]

NINE-MONTH RESULTS

Upsher-Smith assistsin Sawai sales surge

Cardiovascular42.1%

Central nervous system38.7%

Urogenital9.6%

Hormone4.3%

Vitamins1.8%

Others3.5%

Figure 1: Breakdown by therapeutic category of Sawai’s North American sales of¥13.5 billion in the nine months to 31 December 2017 (Source – Sawai)

Zydus’ Moraiya plantcompletes FDA auditZydus Cadila’s key finished-dose formulations facility in Moraiya,

India, has been cleared by the US Food and Drug Administration(FDA) following a five-day inspection earlier this month. Zydus notedthat no ‘Form 483’ observations were issued by the US agency. Ina statement to the Bombay Stock Exchange (BSE), the Indian firmclarified that the audit was “not a surprise inspection”.

At the end of 2015, the FDA issued a warning letter against theMoraiya site after an inspection unearthed deficiencies including afailure to establish written procedures and prevent unauthorisedchanges to data (Generics bulletin, 15 January 2016, page 3).

Around a year ago, the agency completed a follow-up inspectionat the Moraiya facility, issuing zero observations (Generics bulletin, 24February 2017, page 3).

Zydus’ group sales increased by nearly two-fifths – 39% – toRs33.0 billion (US$509 million) in the firm’s financial third quarterended 31 December 2017. Aided by lower excise duties, the company’spre-tax profit more than doubled to Rs7.22 billion. Earnings beforeinterest, tax, depreciation and amortisation (EBITDA) surged by108% to Rs8.41 billion.

Received 24 approvalsIn the US, Zydus received approval from the FDA for 24 products

during the quarter, filed 10 additional abbreviated new drug applications(ANDAs), and launched two products. In its domestic market, the Indianfirm introduced 12 new products, including “four first-in-India launches”.

During the quarter, Zydus received a marketing authorisation fromMexican regulatory agency Cofepris for its Lipaglyn (saroglitazar)treatment for dyslipidemia in patients with type-2 diabetes andhypertriglyceridemia in patients with type-2 diabetes not controlledby statins (Generics bulletin, 24 November 2017, page 12).

Meanwhile, Zydus pointed out that it was “taking its efforts inpublic health and care a step further” by entering into a public-privatepartnership with the Indian Council of Medical Research (ICMR) tolaunch new diagnostic kits – developed by the ICMR’s National Instituteof Virology – to detect neglected infectious diseases in livestock. G

MANUFACTURING/THIRD-QUARTER RESULTS

Iran’s CinnaGen has obtained a good manufacturing practice (GMP)certificate in the European Union (EU) for its local facility in Tehran,

which the firm described as “the first and only full-cycle biologicmanufacturing complex in the Middle East and North Africa (MENA)region”. The plant has a total 60,000 sq m working area, including a15,000 sq m clean room area.

“CinnaGen has two biosimilars in clinical development in Europe,”a spokesperson for the firm told Generics bulletin. Although theidentities of the products were not divulged, the company claims that“both of them will be the first biosimilars to the originators”.

Pointing out that the company had eight manufacturing plants inIran and Turkey, CinnaGen also noted that it was currently engagedin two joint ventures, one in the South-East Asia region and anotherin Latin America. “We are expanding aggressively to other markets,”the Tehran-based firm stated. “Latin America, the EU and Japan areour key target markets.” G

MANUFACTURING

CinnaGen gets EU GMP nod


AAM ANNUAL MEETING

Product-specific guidelines for developing biosimilars in the US“are not possible until we accumulate more knowledge about

the issues”, the US Food and Drug Administration’s (FDA’s) JanetWoodcock told delegates to the annual meeting of the US Associationfor Accessible Medicines (AAM).

Speaking in Orlando, Florida, earlier this month, Woodcock –who is director of the agency’s Center for Drug Evaluation andResearch (CDER) – told AAM delegates that, as analytical toolsbecame more powerful, the agency was still learning about referencebiologics as well as their biosimilar alternatives. “We do not havethese products totally nailed down in terms of characterising them,”she said, adding that the FDA was learning more “about the controlof these products and their variability”.

Given that the FDA was still in the early stages of its biosimilarsprogram – the agency has to date approved nine biosimilars – Woodcocktold delegates not to expect in the near term the standardised reviewprocess towards which the FDA was striving for small-moleculegenerics (see opposite). The agency was, she revealed, taking on morestaff to conduct case-by-case assessments of the several biosimilarapplications that it anticipated receiving. Further guidelines, policiesand possibly regulations would follow, she added.

Meanwhile, the FDA’s ongoing educational outreach to healthcareprofessionals was being “well received”, insisted Woodcock, whodescribed the recent support for biosimilars from the American Collegeof Rheumatology (ACR) as “a big step forward” (Generics bulletin,16 February 2018, page 14). G

REGULATORY AFFAIRS

FDA intends to learnbefore product guides

AUS Food and Drug Administration (FDA) pilot programimplementing standardised, graded processes and categories of

observations from inspections of sterile-drug facilities is to be expandedto cover other dosage forms of all drugs.

Describing improvements to facility assessment and surveillanceduring the recent annual meeting of the US Association for AccessibleMedicines (AAM), Janet Woodcock – director of the agency’s Centerfor Drug Evaluation and Research (CDER) – said the eventual goal ofa new inspection protocol project (NIPP) was to grade observationsso the agency could better communicate its verdict on facilities andclarify any deficiencies. “If you have an outstanding facility, we wouldlike to be able to give you an A+,” she stated, adding that this would“provide better clarity for industry” on what the agency was looking for.

Woodcock said the agency had achieved several goals, such asestablishing an inventory of plants supplying drugs, reorganising itsOffice of Regulatory Affairs (ORA), and notifying facilities of theirstatus within 90 days of concluding an audit.

But improving and integrating knowledge-management betweenthe ORA and other parts of the agency remained a target, as did“developing more sophisticated risk metrics so we can better targethigher-risk facilities” and implementing more standardised inspectionprotocols that would help to harmonise international practices. Workon implementing a mutual-recognition agreement with the EuropeanUnion (EU) on surveillance inspections was continuing, she noted(Generics bulletin, 2 February 2018, page 10). G

REGULATORY AFFAIRS

FDA aims to grade inspections

The US Congress may yet pass this year a Creating and RestoringEqual Access To Equivalent Samples (CREATES) act, even though

brand industry lobbyists succeeded in having a bill removed from theUS Administration’s fiscal 2019 budget, according to Chip Davis,president and chief executive officer of the US Association forAccessible Medicines (AAM).

“My sense is that the midnight-hour move to extract it from thebudget has done a couple of things. It has created a higher level ofconfusion, anxiety and frustration on the part of those that think it isthe right way to go about lowering drug costs by ensuring more robustcompetition,” Davis told Generics bulletin in an exclusive interviewconducted during the AAM’s annual meeting held in Orlando, Florida,earlier this month.

Pointing out that the CREATES act was almost unique in enjoyingsupport from members of Congress at either end of the politicalspectrum, Davis insisted the “only voices” opposing the legislation –aimed at ensuring generics and biosimilars developers had access tothe brand samples they needed for bioequivalence and biosimilaritytesting – were originator companies and the third-party groups that theyfinancially subsidised. There was, he maintained, “a growing chorus”of people who wanted to see the legislation enacted.

Created even more momentum“In being able to extract it from the budget at the last minute, the

branded side may not have anticipated that they have created evenmore momentum for people to continue to pursue it moving forward,”Davis commented, citing feedback the AAM had received. Given theircommitment to tackling drug pricing and competition, the Administrationand Republican party would have to answer for a failure to act beforemid-term elections took place in November this year.

Asked whether he saw any opportunities for the CREATES act –the S.974 bill in the Senate and H.R.2212 bill in the House ofRepresentatives – to pass before the mid-terms, Davis identified “acouple of vehicles that they are going to need to find funding for”.Legislators would, he predicted, look to attach the bill to “things thatare bipartisan and non-controversial”. However, he acknowledged,action would be needed “in the next couple of months” beforecampaigning for the mid-term elections began in earnest.

Discussing the CREATES act in its 2017 annual report releasedduring its annual meeting, the AAM argues that “the broad base ofsupport across the political spectrum reflects the unimpeachable meritsof the bill’s approach to remedying this anti-competitive abuse thathampers generic and biosimilar drug-makers and hurts patients”. “AAMwill continue to advocate for the bill’s passage while fighting offattempts by branded pharma to derail the legislation,” it pledges.

In a white paper entitled ‘Ensuring the future of accessiblemedicines in the US” that the AAM has just published, the associationoutlines how the US Food and Drug Administration (FDA) has to date“received more than 150 complaints” of originators using the agency’srisk evaluation and mitigation strategy (REMS) systems or their ownsafety programs as a rationale for denying generics and biosimilarsdevelopers access to the samples they need. “In the absence of strongpenalties for failing to make samples available to generic developersunder the same terms as any other willing purchaser, such unlawfulbehaviour is likely to continue,” it warns, adding that REMS abusecosts the US healthcare system US$5.4 billion per year. Gn [email protected]

LEGISLATION

CREATES act in USmay still pass in 2018


AAM ANNUAL MEETING

Testing and implementing a more structured, computer-aidedassessment process for abbreviated new drug applications (ANDAs)

will enable the US Food and Drug Administration (FDA) to accelerateapprovals on their first review cycle, according to Janet Woodcock,director of the Center for Drug Evaluation and Research (CDER).

Addressing the annual meeting of the US Association for AccessibleMedicines (AAM) in Orlando, Florida, earlier this month, Woodcockadmitted to delegates that the current trajectory of the ANDA programwas “probably not sustainable under current assessment practices”.

While the FDA was approving record numbers of ANDAs (Genericsbulletin, 16 February 2018, page 10), Woodcock recognised that thenumber of ANDAs received by the agency rose in its 2017 fiscal yearby 54% to 2,849. “We expect this rising trend to continue over thenext several years,” she said. Over the same period, controlledcorrespondence increased by 42% as “questions from industry arebecoming more pointed and detailed, as well as larger in volume”.

“There are still many inefficiencies in the review process underthe Generic Drug User Fee Amendments (GDUFA),” Woodcockadmitted, stressing the need to achieve more first-cycle approvals anddecrease the number of refuse-to-receive notifications (RTRs) tominimise workload on both industry and the FDA. A first-cycle ANDAapproval rate of 12.8% in fiscal 2017 was broadly in line with recenttrends, meaning a large number of filings were sent back to industry forrectification. And while fiscal 2017’s RTR rate of 10.5% was aroundhalf of the 20.9% average between fiscal 2015 and 2017, such rejectionsrepresented “a waste of time and effort for both you and us”.

“The real question for me is how can we revise the program andright-size staffing so we understand the throughput and workload thatgives us a steady state?” she said. The key, she outlined, was givingapplicants clarity on the agency’s expectations and structuring thereview process so that it was more standardised.

At present, Woodcock acknowledged, the application assessmentprocess – particularly pertaining to quality – was “labour-intensive”,with multiple scientists creating text-based documents that were “notvery amenable to knowledge management”. “We do not have verygood visibility in terms of what we have done before, and it is hardfor us to understand the precedents from what we have told similarlysituated applicants,” she admitted.

To tackle this problem, the agency’s Office of PharmaceuticalQuality (OPQ) has developed a knowledge-aided assessment andstructured application (KASA) as “a new paradigm for performingquality assessments of applications”. By adopting a more tabular,structured approach, Woodcock said this would create “consistencyacross what we are asking of applicants” and “remarkably improve theefficiency of processing applications.”

The agency was, she said, currently testing and improving prototypesof computer-aided interfaces and was piloting a “dashboard interface”that was centred around quality risk-assessment for critical qualityattributes and corresponding mitigation strategies, as well as controlstrategies for drug substances and products. “We are putting a fairamount of investment into testing these prototypes,” she explained.“Once we really start utilising and improving them, we will be ableto share them with industry.”

“Ultimately, maybe some years hence, we would like to have amore structured submission that is more based on data than on text,but we are not there yet,” Woodcock concluded. Gn [email protected]

REGULATORY AFFAIRS

Structured reviewswill accelerate ANDAs

Individual member companies within the Association for AccessibleMedicines (AAM) can do more to “control the narrative” around drug

pricing and access, the US industry body’s president and chief executiveofficer, Chip Davis, told delegates to the AAM’s 2018 annual meeting.

Speaking in Orlando, Florida, Davis described the generics andbiosimilars industries as “underdogs”. “Compared to others in thepharmaceutical supply chain, when it comes to public policy andadvocacy, we have far fewer resources,” he pointed out, adding thatoriginators spent US$20-25 for every US$1 invested in such activitiesby generics and biosimilars providers.

Drug costs, he said, were “the number one healthcare issue” inthe US at present, and while generics accounted for almost 90% ofall medicines dispensed in the US, brand companies held around 90%of “the mind-share” in the public policy debate.

Nevertheless, he said the AAM had registered significantachievements since its rebranding from the Generic PharmaceuticalAssociation (GPhA) around a year ago. The association had testifiedseveral times before Congress during 2017 and had also contributedto both a Food and Drug Administration (FDA) workshop on balanceswithin the Hatch-Waxman legislative framework and a joint FDA/Federal Trade Commission (FTC) forum on competition (Genericsbulletin, 3 November 2017, page 13). Furthermore, bills on user feesfor both generics and biosimilars had been ratified, while harmfulproposed changes to labelling had “gone into the deep freeze” as badpolicy. “We got some important wins on biosimilars to ensure thereare appropriate incentives in the marketplace,” he added.

However, 2017 had been “a very challenging year” for industry,Davis said, with “unprecedented sustained periods of price deflationin the generics sector” and continuing consolidation that was tilting “thenegotiating table in favour of buyers”. A rumoured takeover approachby Walgreens Boots Alliance for AmeriSourceBergen threatened tofurther restrict competition in the supply chain, he observed.

Encouraging delegates to band together to “drive our own narrative”,Davis warned that, with US mid-term elections this year, “policy-makers are going to prioritise good politics over good policy”.

“We have the opportunity to do a lot more to advance the valueproposition of the generic and biosimilar sectors of AAM,” Davisinsisted. “Tell your individual story as a business,” he urged, noting howoriginator firms had mobilised rapidly after President Donald Trump’sState of the Union address to deflect blame for rising drug costs onto otherparts of the supply chain. “I do not want anyone but the leaders ofthis industry to be controlling the narrative of this industry,” he stated.

“We have an opportunity to help more leaders get out thereand explain the value proposition of this industry,” he continued.“If we raise the level of engagement now and put more resources inplay, there is nothing we cannot accomplish, because we are on theright side, the side of patients, access and affordability.”

Companies should cultivate relationships with local media toexplain their value proposition and current challenges, Davis proposed.“Invite policy-makers to your offices,” he advised, adding thatpoliticians wanted to understand their constituents’ problems. “Hundredsof millions of patients around the world rely on this industry for safe,affordable and effective medicines,” he concluded. “We have nothingto apologise for.”

The AAM will hold its next annual meeting on 4-6 February 2019in New Orleans, US. Gn [email protected]

INDUSTRY ASSOCIATIONS/PRICING & REIMBURSEMENT

US companies shouldsteer story on pricing


MARKET NEWS

Changes to the US 180-day exclusivity incentive for first-filers ofabbreviated new drug applications (ANDAs) containing paragraph IV

patent challenges have been mooted in a US budget document outliningproposals for the 2019 financial year. Under the proposed measure, atentative approval granted by the US Food and Drug Administration(FDA) for a subsequent generic applicant that is blocked by a 180-dayexclusivity period for the first applicant would trigger the first applicant’sexclusivity period, preventing first-filers from ‘parking’ exclusivity.

Acknowledging that the current 180-day exclusivity frameworkprovides an incentive to generics applicants – thus helping to maketreatments more affordable and increase access to healthcare – thebudget document nevertheless states that “some ‘first filers’ can blocksubsequent generic competitors from receiving approval under thisexclusivity provision”. Similarly, it adds, “first filers that receivetentative approval but then intentionally delay seeking final approvalcan block subsequent competitors”. As a result, “first filers can ‘park’their exclusivity, and consumers are denied access to generic productsand must keep paying the brand price”.

But the new “legislative proposal” mooted by the budget “makesthe tentative approval of a subsequent generic drug applicant that isblocked solely by a first applicant’s 180-day exclusivity – where thefirst applicant has not yet received final approval – a trigger of the firstapplicant’s 180-day exclusivity”. This, the document explains, “meansthe period of exclusivity would immediately begin for the first filer”.

“This proposal will enhance competition and facilitate more timelyaccess to generic drugs,” the budget document insists, adding thatimplementing the measure would generate savings of US$1.79 billionfor Medicare over the next decade. Of these, US$118 million wouldcome in 2019 alone, and US$728 million in the 2019-2023 period.

Also included in the budget is a proposal to “eliminate cost-sharingon generic drugs for low-income beneficiaries”. This “encourages theuse of higher-value products among low-income subsidy enrollees byreducing cost-sharing for generics to US$0, including biosimilarsand preferred multiple-source drugs”. According to the budget, thiswould generate savings of US$30 million in 2019, US$150 millionfrom 2019-2023 and US$210 million in the decade to 2028.

Speaking at the annual meeting of the US Association forAccessible Medicines (AAM), the US Food and Drug Administration’s(FDA’s) deputy commissioner for policy, planning, legislation andanalysis, Anna Abram, said the proposed changes to 180-day exclusivitywould “help address the problem” of barriers to generics reaching themarket. “This proposal will enhance competition, facilitate moretimely access to generic drugs and is expected to create meaningfulsavings,” she insisted.

Acknowledging requests from industry for more information onwho holds 180-day exclusivity, Abram told AAM delegates that“although there is a lot we cannot disclose, we are exploring ways wecan update and expand our paragraph IV website so we can be astransparent as possible”.

The AAM’s president and chief executive officer, Chip Davis, toldGenerics bulletin that, while several details of the proposal were yetto be clarified, the association was concerned by “anything that is seenas weakening the 180-day exclusivity incentive that is the very foundationof Hatch-Waxman”. Given the difficulty of “breaking through patentestates that brand companies are building around their blockbusters”,the proposal could have the effect of “chilling competition”, he warned. Gn [email protected]

REGULATORY AFFAIRS

Second filers in US totrigger 180-day term

Revised guidance on the European Falsified Medicines Directive(FMD) has been set out by the European Commission, a year

ahead of the implementation of safety features and a new medicineverification system on 9 February 2019. An updated question-and-answer document covers safety features, the unique identifier, obligationsof marketing-authorisation holders, and transitional measures.

Newly-added questions include whether bundles of several singlepacks sold as one unit should have anti-tampering devices andidentifiers on each single pack, or on the bundle, as well as whereheaders and data elements should be placed on packaging.

It is not possible to reverse the decommissioned status of amedicine which has been exported to third countries and then broughtback into the European Union (EU), the document states. Such amedicine would be considered an import. Meanwhile, the guidanceconfirms, manufacturers can use outer packaging carrying a uniqueidentifier placed by another contracted manufacturer.

Other newly-added questions cover the use of informationrepositories and data systems, including whether marketing-authorisationholders can delegate the uploading of relevant information to thirdparties. Meanwhile, safety features cannot be waived for free samples.

A specific question related to Annex II for non-prescription drugsaddresses the question of whether omeprazole gastro-resistant tabletsare required to bear the safety features. “Only medicinal productscontaining omeprazole 20mg or 40mg formulated as hard gastro-resistant capsules have to bear the safety features,” the documentspecifies, “as the two reported incidents of falsification which led tocertain omeprazole products being added to Annex II concerned thatspecific pharmaceutical form of omeprazole.” G

REGULATORY AFFAIRS

EU updates guidanceon falsified medicines

Litigation over the legality of the US inter partes review (IPR) processfor pharmaceutical patents has been escalated to the country’s

Supreme Court. United Therapeutics has filed a certiorari petitionasking the court to review its litigation with SteadyMed over Remodulin(treprostinil) US patent 8,497,393, after an IPR held the patent to beinvalid in a decision that was upheld on appeal.

The originator has asked the Supreme Court “whether IPR – anadversarial process used by the Patent and Trademark Office (PTO)to analyse the validity of existing patents – violates the US constitutionby extinguishing private property rights through a non-Article III[court] forum without a jury?”.

United Therapeutics’ petition follows a successful petition filedlast year as part of a dispute between energy companies Oil States andGreene’s (Generics bulletin, 23 June 2017, page 6), for which oralarguments were heard in late November. “Given that this court willaddress the same substantive question in Oil States as in this case,”United Therapeutics urges, “this court should hold this petition, consistentwith its ordinary practice, pending the resolution of Oil States.” If IPRsare found to be unconstitutional in that case, the originator demands,the Supreme Court should grant the certiorari petition relating to thetreprostinil case and vacate and remand the earlier decision.

Patent litigation between United Therapeutics and Teva’s Actavisover the ‘393 patent is set for trial starting in mid-July. G

Pharma IPRs may face reviewINTELLECTUAL PROPERTY


MARKET NEWS

5-6 Marchn EuroPLX 66

Lisbon, PortugalThis two-day meeting provides an opportunity to discuss andnegotiate agreements, development, in-licensing and marketing,promotion and distribution.

Contact: RauCon. Tel: +49 6221 426296 0.E-mail: [email protected]. Website: www.europlx.com.

17-19 Apriln DIA Europe 2018

Basel, SwitzerlandIssues including policy and regulations, research and development,marketing and access will be covered at this three-day event.

Contact: Drug Information Association. Tel: +41 61 225 5151.E-mail: [email protected]. Website: www.diaglobal.org.

25 Apriln 14th Legal Affairs Conference

London, UKThis one-day conference organised by Medicines for Europe willcover legal and intellectual-property developments regardinggenerics and biosimilars. This event will be followed by the 16thBiosimilar Medicines Conference, at the same venue.

Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: [email protected]. Register online atwww.medicinesforeurope.com/events.

26-27 Apriln 16th Biosimilar Medicines Conference

London, UKThis Medicines for Europe conference will look at the latestregulatory topics, market access and procurement, andinternational developments within the biosimilars industry.


23-24 Mayn World Biosimilar Congress USA 2018

San Diego, USAThe agenda for this two-day meeting includes pricing,pharmacovigilance, bioanalytics and patent issues.

Contact: Terrapinn. Tel: +1 212 379 6320.E-mail: [email protected]. Website: www.terrapinn.com.

13-15 Junen Joint Medicines for Europe and

IGBA Annual ConferenceBudapest, HungaryThis joint Medicines for Europe and IGBA three-day conferencewill look at the latest developments within the industry.


EVENTS – March, April, May, June

Tuesday 9 October 2018,Madrid, Spain

SAVE THE DATE...

France has officially ratified the protocol on privileges and immunitiesof the Unified Patent Court (UPC), according to the European

Council. Having published domestic legislation in France’s JournalOfficiel at the very end of 2017 authorising the ratification of theprotocol – which includes the privileges and immunities necessaryfor the UPC to operate – the European Council said the country hadofficially deposited its instrument of ratification on 14 February.

Meanwhile, the UK Privy Council has in early February approvedthe country’s own instrument of ratification, the Unified Patent CourtImmunities and Privileges Order 2018. However, as Generics bulletinwent to press, the European Council had not yet acknowledged anofficial notification of the UK’s ratification.

France and the UK are among four countries – along with Germanyand Luxembourg – that must formally ratify the protocol in order forit to come into force. Germany has not yet ratified the core UPCagreement (Generics bulletin, 8 December 2017, page 7), whileLuxembourg’s draft legislation to ratify the protocol on privileges andimmunities is progressing through parliament. G

INTELLECTUAL PROPERTY

France and UK takeUPC protocol action

Apublic workshop to “provide an overview of the current status ofthe regulatory science initiatives for generic drugs” will be held

by the US Food and Drug Administration (FDA) on 24 May at itsWhite Oak campus in Silver Spring, Maryland, providing “an opportunityfor public input on research priorities”. The FDA said it would usefeedback from the workshop to develop the agency’s regulatory scienceplan in accordance with its commitments under the Generic Drug UserFee Amendments (GDUFA). Requests to attend and make oralpresentations at the workshop may be submitted up to 24 April. G

REGULATORY AFFAIRS

FDA plans science workshop

Details of temporary premises that will be adopted by the EuropeanMedicines Agency (EMA) as it moves from its current headquarters

in London, UK, to its future location in Amsterdam, the Netherlands,have been revealed by the agency. The move follows the UK’s ‘Brexit’decision to leave the European Union (EU).

“The Dutch authorities have committed to building completelynew, tailor-made premises for the EMA in the Zuidas business district,”the agency stated. However, “the building will not be completed by30 March 2019, when the EMA has to be fully operational inAmsterdam”, the date the UK leaves the EU. Temporary premisesare therefore being set up in the Sloterdijk area of Amsterdam.

The temporary premises “will be made available on 1 January2019”, the agency said. “This will allow the EMA to gradually moveall staff to Amsterdam before the end of March 2019.” The agencyinsisted that “this interim solution ensures the EMA’s businesscontinuity in Amsterdam for the limited time until its new permanentbuilding is completed on 15 November 2019”, adding that theNetherlands was committed to ensuring a “seamless transition”. G

REGULATORY AFFAIRS

EMA details interim proposal


PRODUCT NEWS

Celltrion’s Herzuma (trastuzumab) 150mg powder for concentratefor infusion is “now approved for marketing in the 28 member

states of the European Union (EU)”, as well as Norway, Liechtensteinand Iceland, after the biosimilar of Genentech’s Herceptin treatmentfor forms of cancer was approved by the European Commission.

The Korean firm had received a positive opinion from thecommittee for human medicinal products (CHMP) within the EuropeanMedicines Agency (EMA) at the end of last year for metastatic breastcancer, early breast cancer and metastatic gastric cancer indications(Generics bulletin, 22 December 2017, page 13).

In holding a pan-European centralised marketing authorisation,Celltrion joins Samsung Bioepis, which obtained approval last Novemberfor Ontruzant, the first trastuzumab biosimilar approved in Europe.

Celltrion did not provide details on its launch plans or pricingstrategy for Herzuma. Speaking during Genentech parent companyRoche’s full-year earnings call, Daniel O’Day, chief executive officerof Roche Pharmaceuticals, said the originator expected the entry ofHerceptin biosimilars “already sometime in this first quarter”. Rochewas anticipating competition from as many as five European trastuzumabbiosimilars this year, he said.

Nevertheless, O’Day pointed out that Roche had achieved goodpenetration for the subcutaneous injection formulation of Herceptin –“50-60% in the countries where we’ve launched” – and said theformulation was “a very sustainable advantage for healthcare systemsand for patients, at least within a certain price band”.

Pointing to biosimilar competition in Europe for Roche’s MabThera/Rituxan (rituximab) original, which Roche also markets as both anintravenous and subcutaneous formulation, O’Day said Roche “wasnot seeing that price band being violated so far by the [rituximab]competitors at this stage of the launch”. However, he opined, “at somepoint in time, I think they will be”.

Roche recently reported sales of Herceptin formulations in Europethat increased by 2% to SFr2.12 billion (US$2.26 billion) in 2017.This amounted to 30% of global Herceptin sales that advanced by3% to SFr7.01 billion. A supplementary protection certificate (SPC)linked to the UK part of Genentech’s key Herceptin patent – Europeanpatent EP0,590,058 – expired on 28 July 2014.

Celltrion has previously gained European Commission approvalfor its Remsima (infliximab) biosimilar, as well as rituximab biosimilarsunder names including Truxima, Ritemvia, Rituenza and Blitzima.

Separately, Celltrion has published 12-month data from itspersonalised anti-tumour necrosis factor therapy in Crohn’s diseasestudy (PANTS), which indicate the clinical effectiveness, safety andimmunogenicity of the Korean firm’s CT-P13 infliximab biosimilaris “comparable to those treated with” Janssen’s Remicade (infliximab)reference product, as well as adalimumab.

Conducted in the UK, PANTS was a three-year, prospective,observational study that investigated primary non-response, loss ofresponse, and adverse drug reactions to CT-P13, Remicade andadalimumab in 1,610 patients with Crohn’s disease.

“We strongly believe that this type of research is essential todeveloping cost-effective treatment strategies for patients withinflammatory bowel disease in order to maximise benefit,” commentedPANTS investigator, Tariq Ahmad. “The results from PANTS suggestthere are opportunities to optimise the management of anti-TNFtherapies and to prevent treatment failure.” Gn [email protected]

ONCOLOGY DRUGS

Celltrion’s Herzumareceives Europe nod

Sandoz has been handed a setback in its attempts to bring itsbiosimilar of AbbVie’s Humira (adalimumab) to market in the US

by knocking out patents. The US Patent and Trademark Office’s(USPTO’s) Patent Trial and Appeal Board (PTAB) has refused Sandoz’two petitions to institute inter partes reviews of two of the originator’sUS patents shielding the autoimmune diseases brand.

The challenged patents were formulation patent 8,802,100, andmethod-of-treatment patent 9,512,216. In both cases, the PTABfound that there was not a reasonable likelihood that Sandoz “wouldprevail with respect to at least one of the claims challenged in thepetition”, based on the evidence the biosimilars developer presented.Sandoz had attempted to see invalidated 29 claims of the ‘100 patentand 16 claims of the ‘216 patent, in light of a host of prior-art documents.

AbbVie’s formulation patents continue to be problematic for Humirabiosimilar developers, with Amgen, in January 2016, and CoherusBioSciences, in November 2016, having previously seen the PTABdeny their petitions to review related US patents 8,916,157 and 8,916,158(Generics bulletin, 22 January 2016, page 13) and 9,114,166 (Genericsbulletin, 11 November 2016, page 13) respectively.

Sandoz’ 351(k) biologics license application for the firm’s GP2017adalimumab candidate was accepted for filing by the US Food andDrug Administration (FDA) at the beginning of this year (Genericsbulletin, 19 January 2018, page 10). Amgen is able to launch its Amjevita(adalimumab-atto) biosimilar in the US from 31 January 2023 undera settlement agreement (Generics bulletin, 6 October 2017, page 1). G

AUTOIMMUNE DISEASES TREATMENTS

Sandoz’ US Humirapetitions are refused

Up to the minute live retail market pricing is availablefor the UK and Eire on Wavedata Live at wavedata.net.Alternatively, contact Charles Joynson at WaveData Limited, UK.Tel: +44 (0)1702 425125. E-mail: [email protected].

Amlodipine tablets tumbleAmlodipine maleate 5mg and 10mg tablets saw their average

UK trade prices dip by around three-fifths in mid-February,according to the latest figures reported by WaveData. Comparingaverage UK trade prices between 1-31 January 2018 and 1-20February 2018, the lower strength dropped by 62% to £0.77(US$1.08) while the higher saw a fall of 60% to £0.81. The lowestoffers for the presentations respectively declined by 69% to £0.62and by 66% to £0.68.

Meanwhile, ethinyestradiol/levonorgestrel 30µg/150µg tabletsin 63-tablet packs saw the highest increase registered by WaveDatain mid-February, leaping by 443% to £15.30. And packs of fivediamorphine powder for solution 30mg vials experienced an averageprice increase of 440% to £80.99.

Nifedipine extended-release 60mg tablets in 28-count packssaw their average price jump by 406% to £29.22, while the samesize packs of irbesartan tablets in two strengths – 300mg and 150mg –saw rises of 219% to £5.33 and 191% to £3.37 respectively.

Elsewhere, gliclazide modified-release tablets experiencedan average price increase of 190% to £6.60 – based on averagescalculated from at least 37 data points – and buprenorphine sublingual8mg tablets in packs of seven rose by 124% to £4.11. G

PRICE WATCH ....... UK


PRODUCT NEWS

Amneal’s US generic version of Merck & Co’s Nasonex (mometasonefuroate) nasal spray was correctly found by a Delaware district

court to not infringe the originator’s US formulation patent, the USCourt of Appeals for the Federal Circuit has ruled. The case revolvedaround Merck’s US patent 6,127,353, which expires on 3 April thisyear, including six months of paediatric exclusivity (Generics bulletin,10 February 2017, page 15).

The ‘353 patent covers mometasone fuorate monohydrate, whichwas developed by the originator as an improvement on the previousanhydrous mometasone furoate formulation. At issue was whetherAmneal’s version of the 50µg mometasone spray – which uses anhydrousmometasone furoate – contained or would contain the monohydrateversion during the product’s two-year shelf-life.

Merck had argued on appeal that the district court should havecompelled Amneal to produce additional samples of its abbreviatednew drug application (ANDA) product for testing, and that the court’sdecision was not based on Amneal’s final commercial product. Theoriginator also challenged the methods of analysis used to determinenon-infringement by Amneal’s version.

Several examples of Amneal’s product were referred to at trial:a ‘day 1 batch’ drawn from a batch on the first day; a ‘day 4 batch’drawn from the same batch on the fourth day, after additional mixing;and an ‘A batch’ drawn after further mixing and bottling for storage.Only samples of the ‘day 1’ product were provided to Merck at thediscovery stage of the trial, with Amneal indicating that these wererepresentative of the finished commercial product. But on appeal, theoriginator claimed it could not prove conversion without testing the‘day 4’ and ‘A batch’ samples.

However, the appeals court said it could “discern no clear error inthe district court’s finding that the trial evidence failed to demonstratethat the anhydrous mometasone furoate in Amneal’s product wouldhave converted to mometasone fuorate monohydrate”.

Merck had presented “little more than theoretical evidence to showthat the ‘day 4’ and ‘A batch’ samples would be more likely to undergoconversion than the ‘day 1’ batch samples”, the court observed, notingthat “Merck’s evidence merely supported that anhydrous mometasonefuroate could convert to mometasone fuorate monohydrate by additionalmixing”, with “no attempt to prove that Amneal’s product wouldconvert simply by the additional mixing Amneal performed”.

In particular, the appeals court noted, “Merck had samples ofAmneal’s exhibit and ‘day 1’ batches, but made no attempt toexperiment with Amneal’s ANDA product to demonstrate conversionby additional mixing and passage of time alone, let alone by matchingthe mixing, in both speed and duration, that Amneal carried out toarrive at the ‘day 4’ and ‘A batch’ samples”.

Acknowledging that “Amneal’s failure to abide by the standingdiscovery order resulted in a trial situation that was less than ideal”,the appeals court nevertheless found that the district court “tookadequate steps to ensure that proceeding with trial would not prejudiceMerck”. And having discerned “no clear error in the district court’s fact-finding of non-infringement”, the district court’s decision was upheld.

Amneal launched its rival to Nasonex in April 2017, shortly afterthe district court ruling (Generics bulletin, 21 April 2017, page 15).Apotex holds the only other US Food and Drug Administration (FDA)approval for a US generic, having launched its version a year earlier(Generics bulletin, 1 April 2016, page 10). Gn [email protected]

ALLERGY REMEDIES

Amneal gets backingon US Nasonex rival

MYLAN has secured tentative approval under the US President’sEmergency Plan for AIDS Relief (PEPFAR) for dolutegravir/emtricitabine/tenofovir alafenamide 50mg/200mg/25mg tablets.Mylan said the unique antiretroviral – approved through the hybrid505(b)(2) pathway – was “the first time a product combinesdolutegravir and tenofovir alafenamide”, the individual componentsof Viiv’s Tivicay (dolutegravir) and Gilead’s Descovy (emtricitabine/tenofovir alafenamide) patent-protected brands. Using patentlicenses granted by Gilead and the Medicines Patent Pool, Mylanplans to supply the once-daily treatment immediately in developingcountries as 30-day and 90-day tablet packs, thereby setting “a newstandard for affordable access in countries hardest hit by HIV”.

PHARMAC – New Zealand’s pharmaceutical management agency –is seeking feedback by 27 February on a proposal to broaden from1 April funded access to montelukast 4mg, 5mg and 10mg tablets.By removing certain indication-based restrictions, the reimbursementbody aims to “enable prescribing of fully-funded montelukast tabletsto any eligible patients that the prescriber considers would clinicallybenefit from treatment for a number of new indications” such asallergic rhinitis. From 1 March, Pharmac will also fund Truvada(emtricitabine/tenofovir) for pre-exposure prophylaxis (PrEP).

LUPIN has obtained from a Maryland district court a summaryjudgement of non-infringement against US patents 9,526,734 and9,649,318 protecting Iroko’s Vivlodex (meloxicam) osteoarthritiscapsules to 2033 and 2035 respectively. The patents cover particlesize of meloxicam. Having found that the particle sizes found inLupin’s generic did not literally infringe the ‘734 and 318 patents,Judge Marvin Garbis also barred Iroko and affiliate iCeutica fromarguing infringement under a doctrine of equivalents as performingessentially the same function as the patented invention. Lupinconvinced Garbis that the plaintiffs had surrendered any rights toprotect certain particle-size ranges in the course of obtaining the patents.

SUN PHARMA has secured clearance in Germany to market bothimipenem/cilastatin 500mg/500mg ampoules as well as Odomzo(sonidegib) 200g capsules. Other recent approvals in Germanyinclude fulvestrant pre-filled syringes from Betapharm, noradrenalinesolution for infusion from Aguettant, rasagiline tablets fromGlenmark and tenofovir disoproxil coated tablets from Amneal.

AUROBINDO has received final US approval for sumatriptan/naproxen 85mg/500mg tablets equivalent to Pernix’ Treximetmigraine treatment. Pernix responded by launching an authorisedgeneric through its Macoven subsidiary.

CELLTRION AND HOSPIRA have been told by MassachusettsDistrict Judge Mark Wolf to reserve from 30 July to 1 October thisyear “for final pre-trial activities and trial” in the Korean firm’sdispute with Janssen over the Inflectra (infliximab) biosimilar toRemicade. Fact witness depositions in the case concerning Janssen’sUS cell-culture media patent 7,598,083 are due to be completedthis month under the terms of a scheduling order issued by Wolf.

PERRIGO has been sued by Bayer in a Delaware district court afterfiling a paragraph IV challenge to US patents protecting the Germangroup’s Finacea (azelaic acid) 15% foam. The Orange Bookmaintained by the US Food and Drug Administration (FDA) listsseven patents against Finacea foam with expiry dates ranging betweenSeptember 2019 and January 2029. Perrigo said US sales of theFinacea topical form for treating inflammatory papules and pustulesof mild to moderate rosacea totalled US$54 million last year. G

IN BRIEF


PRODUCT NEWS

Canada denies chanceto choose on damagesPatent infringers in Canada do not have the right to elect to account

to pay an accounting of its profits, rather than damages, the country’sFederal Court of Appeal has ruled in a decision denying Apotex’appeal over Bayer’s Yasmin and Yaz (drospirenone/ethinylestradiol).

In September 2016, a lower court found that Apotex’ Zamineand Mya oral contraceptives infringed Bayer’s Canadian patent2,382,426. A few weeks later, the judge held that Bayer, not appellantApotex, was entitled to choose what remedy was appropriate.

On appeal, Apotex argued that sub-section 57(1) of the PatentAct – which authorises a court to issue infringement orders “on theapplication of the plaintiff or defendant” – allowed defendants tochoose to pay “an accounting of profits after a finding of infringement”.

While the Court of Appeal agreed with Apotex that the applicablestandard of review was correctness as a question of law, it describedthe generics firm’s other arguments as “without merit”. “The propositionthat the infringer can determine the remedy to which a patentee isentitled is an astounding proposition,” lead judge Marc Nadoncommented. “What the appellant truly seeks is, in effect, to imposeupon the respondents the remedy of an accounting of profits, even ifthey do not want it,” he said, pointing out that Apotex had been “unableto point to a single case where an infringer was given the right to electthe remedy which should be granted to an aggrieved patentee”.

“The inclusion of the word ‘defendant’ in sub-section 57(1) ofthe [Patent] Act does not give the court the power to grant an electionto a defendant following a finding of infringement,” Nadon stated.

In a separate ruling, the Court of Appeal confirmed damagesof C$18.8 million, plus costs of C$1.00 million, awarded againstTeva for infringing Canadian patent 1,304,080 protecting the Levaquin(levofloxacin) antibiotic that Janssen licenses from Daiichi Sankyo. G

ORAL CONTRACEPTIVES/ANTIBIOTICS

Biocad has plans toship Remicade rivalBiocad has announced plans to begin shipping the firm’s biosimilar

of Janssen’s Remicade (infliximab) to “global markets” towardsthe end of this year, or in early 2019.

“India, where the market for infliximab amounted to US$42 millionin 2017, is expected to be the first country to receive shipments,” theRussian company revealed. Analysts were forecasting infliximabsales of up to US$50 million this year in India, Biocad noted.

The announcement came as Biocad disclosed that the firm’sBCD-055 infliximab biosimilar has been approved by regulators inits local market, having been “proved equivalent” to Remicade “ininternational clinical trials”.

“The approval was based on comprehensive pre-clinical andclinical data that proved the biosimilarity of infliximab biosimilar [to]Remicade. The therapeutic effects of Biocad’s infliximab biosimilarhave been shown equivalent to the effects of the originator, and thesafety profiles of two drugs were similar, even in the long-term.”

Biocad said it had carried out its clinical studies of the infliximabbiosimilar “in compliance with the most recent international guidelines,including the European Medicines Agency’s (EMA’s) guidelines onnon-clinical and clinical investigation of similar biological medicinalproducts containing monoclonal antibodies” (Generics bulletin, 29June 2012, page 15).

Following approval in Russia, the firm’s infliximab biosimilar isthe fourth monoclonal antibody to have obtained regulatory approval,after biosimilars of Genentech’s Avastin (bevacizumab) and Herceptin(trastuzumab) and Roche’s MabThera/Rituxan (rituximab). All threebiosimilars are manufactured in Biocad’s local Neudorf facility, set ina special economic district outside St Petersburg.

The Russian firm noted that in 2016 and 2017 it had begunexporting these biosimilars “to international markets, significantlyreducing the cost of cancer treatment for patients in South East Asia,North Africa and Latin America”.

“Recently, the demand for Biocad’s products has significantlyincreased in Vietnam, Sri Lanka, and Morocco,” said Biocad. “In thenear future, Biocad will export its products to India, Cuba and Egypt.”

Biocad pointed out that it already co-operated with partners “from50 countries in Europe, Asia, Latin America and North and SouthAfrica”. “The company is planning to increase the share of its exportcontracts to 50% from the total contract amount within the next fiveto six years,” the Russian player revealed.

Earlier this year, Biocad forecasted that the firm’s adalimumabbiosimilar would be available to patients in Russia at the end of thisyear or the beginning of 2019, and at a price “at least a quarter less”than AbbVie’s Humira (adalimumab) original.

The Russian firm’s predictions came as it announced it hadcompleted the “main phase” of its ‘Calypso’ Phase III clinical trialcomparing Biocad’s BCD-057 adalimumab candidate against Humirain patients with moderate-to-severe plaque psoriasis.

Furthermore, Biocad recently completed clinical trials forBCD-066, the first darbepoetin alfa biosimilar in Russia.

Results from a Phase I and Phase III comparative study demonstratedtherapeutic equivalence between the firm’s treatment for anaemiapatients with chronic renal failure and cancer and Amgen’s referencebrand Aranesp (darbepoetin alfa) in terms of pharmacodynamics,pharmacokinetics, efficacy, safety, and immunogenicity. Biocad saidit expected to launch the biosimilar “at the end of 2018”. Gn [email protected]

AUTOIMMUNE DISEASES TREATMENTS

Hungary’s Egis Pharmaceuticals has furthered its strategy ofgrowing in “major export markets”, including through acquisitions,

after buying “all rights related” to the Sinuforte (cyclamen extract)nasal spray treatment for sinusitis and other inflammatory diseasesfrom the Hartington Group’s Spain-based Hartington Business affiliate.

“As per the agreement, Egis receives all rights related to theproduct, including the rights to commercialise in Russia andCommonwealth of Independent State (CIS) countries,” Egis revealed,adding that the OTC brand had a “meaningful size” in these markets.The agreement also covers “the patent related to the production methodof the active pharmaceutical ingredient and the finished product”.

Noting that Sinuforte – known as Nasodren in other markets – was“expected to be a leading product of the Egis portfolio in Russia”, Egissaid it had “already started the distribution of Sinuforte” in the market,as well as Kazakhstan, Ukraine, Belarus and Georgia during last year.

“Sinuforte has strong fit with Egis’ current portfolio and operations,supported by Egis’ traditionally trusted relations with local professionals,”the Hungarian firm commented. “Egis expects the substantial growthof Sinuforte by increasing the awareness of the disease and the product’scharacteristics among healthcare professionals and patients, contributingto successful therapies, satisfying an unmet medical need that affectsa large patient population.” G

SINUSITIS TREATMENTS

Egis acquires Sinuforte rights


PEOPLE

LUPIN has appointed Shawn Brown as vice-president of governmentaffairs, based in Washington DC, US. Brown had been president ofconsultants SMB Strategies after leaving his government affairs roleat Allergan in 2016. He also spent several years working on state affairsand policy at the US Generic Pharmaceutical Association (GPhA).

CARDINAL HEALTH has elected Akhil Johri, executive vice-president and chief financial officer of United Technologies, to thefirm’s board of directors. He has also joined the board’s auditcommittee. With the addition of Johri, Cardinal Health noted that itsboard now consisted of 13 directors, 11 of which are independent.

VETTER PHARMA has named Michael Yi as business developmentmanager of the company’s new branch office in Songdo, South Korea.Vetter officially opened the office in November last year as part ofits plans to “strengthen its global footprint in the Asia-Pacific region”.

MALLINCKRODT has appointed Mark Casey as general counsel,effective immediately. He will join the firm’s executive committee,reporting directly to president and chief executive officer, MarkTrudeau. Casey’s primary office will be located in the US firm’slocal facility in Bedminster, New Jersey, which houses Mallinckrodt’sSpecialty Brands business and related research and developmentstaff. Citing Casey’s 10 years of experience as a healthcare industrygeneral counsel, Mallinckrodt said he had an “extensive backgroundin international business; litigation management across a range ofmatters; acquisitions and divestitures; and deep experience inintellectual property, regulatory and legal strategy”.

ALLERGAN has named Matthew Walsh as executive vice-presidentand chief financial officer. The firm said he would “formally joinAllergan later this month following a transition period from hiscurrent role as executive vice-president and chief financial officerat Catalent”. During his 10-year tenure at Catalent, Walsh “led theirtransformation under private equity, a successful initial public offering,and numerous acquisition and divestiture transactions”. G

IN BRIEF

DEVELOP WINNINGDISTRIBUTION STRATEGIES

OTC DISTRIBUTION IN EUROPE2018 EDITIONDISRUPTIONCHANGESTHE PLAYING FIELD

Available soon to download or orderonline at www.james-dudley.co.uk

®

JAMES DUDLEYMANAGEMENT ®

Now in its 11th edition, thisin-depth study identifies thefactors driving change in thesupply network serving Europe’snon-prescription and OTCself-medication sectors.

It provides a commmppprrreeehhheeennnsssiiivvveee,data-driven analysis of theunfolding strategies required toachieve competitive success.

OVER 20 COUNTRIES AND 300GRAPHS, TABLES & FIGURES

Apotex’ founder and chairman, Barry Sherman, has posthumouslybeen awarded a Champions of Access award by the US Association

for Accessible Medicines (AAM).Accepting the award on Sherman’s behalf during the AAM’s

recent annual meeting held in Orlando, US, Apotex’ president andchief operating officer, Jeff Watson, contrasted the “great honour”bestowed on Sherman with the “great sorrow” he and his colleaguesfelt after Sherman’s death in December last year (Generics bulletin,22 December 2017, page 1).

“Barry was a visionary and a trailblazer throughout his 44 years inthe industry,” Watson declared. He highlighted Sherman’s passion for“over-spending” on research and development and his ability to takeinnovative approaches to litigating intellectual property in a bid to broadenaccess to medicines, as well as his philanthropy. “We will continue topush forward with his legacy as an organisation,” Watson promised.

The AAM also handed a Champions of Access award to theAmerican Cancer Society. G

INDUSTRY ASSOCIATIONS

AAM awards honourto Apotex’ Sherman

Slovakia-based contract development and manufacturing organisation(CDMO) Saneca Pharma has named Richard Král as its new chief

executive officer, replacing former chief Anthony Sheehan. Král –who has been sales and marketing director at Saneca for nearly threeyears – “will be responsible for implementing Saneca’s business growthstrategy, driving operational efficiency and ensuring effective projectdelivery across the business”.

With “over 17 years’ experience in the pharmaceutical sector andfast-moving consumer goods”, Král has previously worked for companiesincluding GlaxoSmithKline and Zentiva, across the Central and EasternEurope (CEE) and Commonwealth of Independent States (CIS) regions.

Aiming to be ‘go-to CDMO’“Over the last three years I have developed a comprehensive

understanding of the company,” Král stated, “and I am looking forwardto continuing to drive its success and establishing Saneca as the go-toCDMO in Europe.” In particular, he pointed out, “I have a lot ofexperience in the CEE market, where Saneca is based”.

Insisting that Saneca’s “technical agility and ability to cater for theentire drug lifecycle really set it apart from its competitors”, Král saidthe firm intended to “continue our strong growth as we progressthrough 2018, and it will be extremely rewarding to see the companycontinue to expand in my new position as chief executive officer”.G

APPOINTMENTS

Saneca selects Král toreplace chief Sheehan

Documents

US originators slam EU on SPC waiver proposal · Richter'sEsmya Zydus'Moraiyaplant 7 completesFDAaudit Upsher-SmithassistsinSawaisalessurge 7 ... on its watchlist in its upcoming