VOLUME 35 ISSUE 12 JULY 2018 - Marketing Research Bureau€¦ · * Reflecting strong global demand for human polyvalent immunoglobulin products, HAEMONETICS reported 10.6% growth

Notice: International Blood/Plasma News© is Protected by Copyright Law. Reproduction or Photocopy of Any Part Without The Publisher‘s Permission is Prohibited by Law.

ISSN 0742-7719

EDITOR: KEITH BERMAN PUBLISHER: PATRICK ROBERT

Published by: The Marketing Research Bureau, Inc. 284 Racebrook Rd. Orange, CT 06477

VOLUME 35 ISSUE 12 JULY 2018

BUSINESS BRIEFS 166

BLOOD & BIOTECHNOLOGY 171

RESEARCH & DEVELOPMENT 173

PRODUCT SAFETY UPDATE 174

PEOPLE 175

NEW PRODUCTS 176

RECENT U.S. PATENTS 177 MEETINGS / SUBSCRIPTION FORM 180

____________________COMPANIES IN THIS ISSUE__________________ACCELERON PHARMAADMA BIOLOGICSALKAHESTAMAG PHARMACEUTICALSARSANIS BIOSCIENCES GmbHARTHREXBAYER HEALTHCAREBIO PRODUCTS LABORATORYBIOPROTEIN TECHNOLOGIESBIOVERATIVCCRE HOLDINGSCELGENECERUSCHINA BIOLOGICSCITIC CAPITAL HOLDINGSCORD BLOOD REGISTRYCORD:USE CORD BLOOD BANKCRISPR THERAPEUTICSCRTS des ArméesCRYO-CELL INTERNATIONALCSL BEHRINGDOVA PHARMACEUTICALSGI PARTNERS

GRIFOLSHAEMONETICSHARPOON THERAPEUTICSHEMARUS THERAPEUTICSICERINSERMJEFFREY MODELL FOUNDATIONNOVO NORDISKOCTAPHARMAPHARMINGPLATODREGEN LABS SAROCHERUBIUS THERAPEUTICSSANGAMO THERAPEUTICSSANQUINSHIRESHIRE SINGAPORESK CHEMICALSTERUMO BCTVERTEX PHARMACEUTICALSVFMCRPVIFOR PHARMA

international blood/plasma news

JULY 2018

Page 166

BUSINESS BRIEFS

* Reflecting strong global demand for human polyvalent immunoglobulin products, HAEMONETICS reported 10.6% growth in fourth quarter revenues for its Plasma busi-ness unit, to $111.6 million from $100.9 million in the same period in 2017. Plasma business revenues for the full fiscal year ended March 31, 2018 increased by 6.7%, or by 7.1% on a con-stant currency basis. Specifically for the North American market, Plasma business revenue growth was 14.2% in the fourth quarter and 8.5% for fiscal year 2018. Fourth quarter fiscal 2018 operating income was $14.3 million (with an operating margin of 6.1%), compared with an operating loss of $57.5 million in the prior year quarter (and an operating margin of -25.2%).

“In fiscal 2018, we focused on reorganizing and transforming our company. We launched our Complexity Reduction Initiative, strengthened our talent base and received key regulatory clear-ances in our Plasma business,” said Haemonetics’ CEO Chris Simon. “We enter fiscal 2019 with confidence in our planned product launches and company-wide productivity efforts, and we are poised for accelerated growth.”

* ADMA BIOLOGICS announced the closing of a public offering of 8,368,200 shares of its com-mon stock at a public offering price of $4.78 per share. The gross proceeds from the offering are approximately $40 million before deducting underwriters’ discounts and commissions and other offering expenses. Included among planned uses of net proceeds are (1) continued remediation and ongoing improvement and enhancements at its plasma fractionation facility located in Boca Raton, Florida, (2) to submit a Prior Approval Supplement for, and re-launch of, Bivigam, (3) to resubmit the Biologics License Application (BLA) for its intravenous immunoglobulin product candidate, RI-002.

* The U.S. FDA announced that an emergency use authorization (EUA) has been granted to the U.S. Department of Defense (DoD) to enable the emergency use of Pathogen-Reduced Leukocyte-Depleted Freeze-Dried Plasma (“French FDP”) manufactured by the Centre de Transfusion Sanguine des Armées. Under this EUA, the use of French FDP is authorized for the treatment of hemorrhage or coagulopathy of U.S. military personnel during an emergency involving agents of military combat (e.g., firearms, projectiles, and explosive devices) when plasma is not available for use or when the use of plasma is not practical. Hemorrhage, sometimes accompanied by coagulopathy, is the leading cause of preventable deaths among combat trauma casualties.

French FDP can be used following reconstitution in settings where refrigeration is not available, thus enabling the rapid availability of plasma for use at the point of injury. Prior to freeze-drying, the product is pathogen reduced using CERUS’ INTERCEPT System for Plasma. It can be stored for up to two years from the date of manufacture at temperatures between 2°C (36°F) and 25°C (77°F).

“Through our collaborative program with the DoD, they’ve made clear the importance of access to freeze-dried plasma in initial efforts to control hemorrhage from battlefield trauma. Granting this authorization will support access to this important product in the event it’s needed,” said U.S. FDA Commissioner Scott Gottlieb, MD.


JULY 2018

Page 167

* CHINA BIOLOGICS’ board of directors has received an unsolicited, preliminary, non-binding letter from CCRE HOLDINGS, a wholly-owned subsidiary of CITIC CAPITAL HOLDINGS, proposing to acquire all of the outstanding shares of the company not already owned by CITIC for $110 in cash per share, or about $3.7 billion. In a news release, China Biologics’ board said it is “reviewing and evaluating CITIC’s proposal and no decisions have been made with respect to the Company’s response to the proposal,” and that “there can be no assurance that any definitive offer will be made, that any agreement will executive or that this or any other transaction will be approved or consummated.”

* The U.S. FDA has approved BIO PRODUCTS LABORATORY’S Biologics License Application (BLA) for new 5% and 25% human albumin products, to be marketed under the name ALBUMINEX. The 5% solution is approved in 250 mL and 500 mL glass vials, and the 25% solution is approved in 50 mL and 100 mL glass vials. Both products are indicated for hypovolemia, ascites, hypoalbuminemia including from burns, acute nephrosis, acute respiratory distress syndrome and cardiopulmonary bypass.

* Cambridge, Massachusetts-based RUBIUS THERAPEUTICS announced pricing of its initial public offering of 10,483,000 shares of common stock at a public offering price of $23.00 per share. In addition, Rubius has granted its underwriters a 30-day option to purchase up to an ad-ditional 1,572,450 shares at the IPO price, less underwriting discounts and commissions. Gross proceeds from the offering are expected to be $241.1 million. The company’s shares will trade on the NASDAQ Global Select Market under the ticker symbol “RUBY.”

Rubius plans to use $95 million of the IPO proceeds to purchase and renovate a facility to manu-facture Red Cell Therapeutics (RCTs), applying its proprietary Rubius Erythrocyte Design (RED) platform. The RED platform genetically engineers and cultures CD34+ hematopoietic precursor cells from O-negative blood donors to express biotherapeutic proteins within the RCT cell or on the cell surface. About $42 million will reportedly be used to finance a Phase 1/2a clinical trial of its lead product, RTX-134, intended as a treatment for phenylketonuria (PKU); the company plans to file an Investigational New Drug application (IND) for RTX-134 during the first quarter of 2019. Remaining proceeds will fund additional R & D activities, including preclinical development of RCTs to treat certain rare diseases, cancers and autoimmune diseases.

Prior to this IPO, Rubius had raised approximately $240 million, most recently including a $100 million crossover financing in early 2018 (see the March 2018 issue of International Blood/Plasma News).

* GI PARTNERS, a private equity investment firm, announced that it will acquire CORD BLOOD REGISTRY (CBR) from AMAG PHARMACEUTICALS for $530 million in an all-cash sale. The parties expect to close the transaction in the third quarter of 2018. Reportedly the world’s largest cord blood collection and storage firm, CBR currently stores cord blood stem cell samples from more than 600,000 children. Subject to customary closing conditions and regulatory approvals, the transaction is expected to close in the third quarter of 2018.


JULY 2018

Page 168

* Separately, privately-held CRYO-CELL INTERNATIONAL announced that it has entered into an agreement to acquire Florida-based CORD:USE CORD BLOOD BANK for $14 million in cash and the issuance of common shares.

* The U.S. Institute for Clinical and Economic Review (ICER) is currently assessing the comparative clinical effectiveness and economic outcomes of three approved C1 esterase inhibitor therapies and one investigational agent for the prevention of hereditary angio-edema attacks. This review will focus on long-term prophylaxis of patients with hereditary angioedema types 1 and 2. The approved products include HAEGARDA (CSL BEHRING), CINRYZE (SHIRE) and RUCONEST (PHARMING) and the investigational product is Shire’s lanadelumab, an investigational monoclonal antibody targeting plasma kallikrein that is currently under review by the U.S. FDA; an approval decision for lanadelumab is expected by September 21, 2018.

A Draft Evidence Report is scheduled to be released on October 11, 2018, followed by a meeting for Evidence Presentation two weeks later, and publication of the Final Evidence Report and Meeting Summary on November 15, 2018.

* Separately, a newly published analysis by the U.S. Institute for Clinical and Economic Review (ICER) reached several conclusions favoring the use of ROCHE’S Hemlibra (emi-cizumab) over bypassing agents (BPAs) as prophylaxis in persons with hemophilia A with inhibitors for whom immune tolerance induction (ITI) has been unsuccessful. In particular, prophylaxis with emicizumab:

• Substantially reduces bleeding events compared to prior prophylaxis with BPAs;• Significantly improves health-related quality of life and caregiver burden;• Improves school and work attendance and reduce hospitalized days; and • Results in overall lower costs than BPAs (estimated annual savings of $1.85 million in

patients >12 years of age and $720,000 in patients <12 years of age.)

The complete ICER report can be accessed at https://icer-review.org/wp-content/uploads/2017/08/ICER_Hemo_RAAG_041618.pdf.

* Mircera, VIFOR PHARMA’S methoxy polyethylene glycol-epoetin beta erythropoiesis-stimulating agent (ESA) indicated for treatment of chronic kidney failure-associated anemia in adults, has received an additional U.S. indication for the treatment of pediatric patients five to 17 years of age on hemodialysis who are converting from another ESA (epoetin alfa/beta or darbepoetin alfa) after their hemoglobin level has been stabilized with an ESA. The product is distributed in the U.S. through joint venture company Vifor Fresenius Medical Care Renal Pharma (VFMCRP).

__________________________________________________________________________________________

Publishers of International Blood/Plasma News© are careful to report accurately from sources believed reliable, but cannot assume liability for any information published. Errors will be promptly corrected when discovered.


JULY 2018

Page 169

The Marketing Research Bureau is pleased to announce the completion of the following research report:

THE PLASMA PROTEINS MARKET IN THE UNITED STATES - 2017

This report is a comprehensive market analysis of the therapeutic plasma and recombinant proteins sold in the U.S. in 2017. It provides sales data and historical trends, in units, dollars and market shares by company. Regulatory, economic and health care issues impacting the market are also discussed. The following topics are covered in the report:

• Plasma Collections and Fractionation

• Overview of the Plasma-derived and Recombinant Proteins Market

• Intravenous, Subcutaneous & Intramuscular Immune Globulins (Polyvalent and Specific)

• Albumin Products

• Factors VIII and IX (Plasma-derived and Recombinant, including Extended Half-life Products and New Non-factor Therapies

• Activated Prothrombin Complex, Recombinant Factor VIIa & Other Coagulation Factors

• Other Plasma-Derived Therapeutic Proteins:

} Alpha-1 Antitrypsin } C-1 Esterase Inhibitor } Fibrin Sealant

} Antithrombin III } Protein C } Thrombin

} Fibrinogen } Factor XIII

• Product Distribution Channels

• Profiles of the Major U.S. Fractionators

To order or to receive more information:

Phone: (203) 799-0298 Email: [email protected] ___________________________________________________________________________________

* The U.S. FDA has approved a new 3500 international unit (IU) vial size for IDELVION [Coagulation Factor IX (Recombinant, Albumin Fusion Protein (rFIX-FP], CSL BEHRING’S long-acting recombinant albumin fusion protein indicated for the treatment of hemophilia B. For patients who require high doses of IDELVION, the new 3500 IU vial size will reduce the reconstitution time needed to prepare multiple vials for a similar dose. “IDELVION is the first and only FDA-approved factor IX therapy that delivers zero median AsBR (annualized spontaneous bleeding rate) and is approved for up to 14-day dosing in appropriate patients,” CSL Behring said in a press release. In a pivotal clinical trial, IDELVION therapy achieved a mean factor IX level of 21% at steady state with prophylactic use, and 5% over 14 days with a single dose.

“Reconstituting the same amount of factor from a single vial will require less diluent than recon-stituting multiple vial sizes, saving patients time and ancillary supplies,” noted Jerry Powell, MD, CSL Behring’s coagulation medical director for North America. IDELVION is now available in 250 IU, 500 IU, 1000 IU, 2000 IU and 3500 IU vial sizes.


JULY 2018

Page 170

* In Sri Lanka, the Ministry of Health, Nutrition and Indigenous Medicine has awarded its latest albumin tender to SHIRE SINGAPORE. The order comprises 120,000 50 mL vials of BP/PH EUR 20% purchased for $2.82 million ($2.35 per gram).

* TERUMO BCT’S Spectra Optia Apheresis System has received the CE mark with an indica-tion to treat Guillain-Barré syndrome (GBS) and myasthenia gravis (MG). Spectra Optia is the first device approved in Europe to treat GBS and MG using therapeutic plasma exchange (TPE). The expanded use indications were based on review of clinical studies demonstrating that TPE therapy resulted in increased speed of recovery for the majority of GBS and MG patients when compared to supportive care.

* In a move to preemptively address the risk of transfusion-transmitted infectious diseases caused by emerging pathogens, the U.S. Department of the Navy has decided to implement pathogen reduction technology for all apheresis platelets collected at Navy Blood Donor Centers. All seven U.S. Navy FDA-licensed blood collection centers worldwide will be required to implement the policy to pathogen-reduce platelet components by December 31. In justifying this decision, the Navy’s Bureau of Medicine and Surgery (BUMED) cited the recent history of emerg-ing pathogens that have threatened the blood supply, including Zika Virus, Ebola, Chikungunya, Dengue and Babesia.

The new policy issued by BUMED requires that all apheresis platelets collected by Navy Blood Donor Centers must be pathogen-reduced using an FDA-approved pathogen reduction system. CERUS’ INTERCEPT Blood System is currently the only FDA approved pathogen reduction system commercially available in the U.S. to treat platelets, and is currently in routine use at the Navy Blood Donor Center at Walter Reed National Military Medical Center in Bethesda, Maryland.

* The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the granting of European Union mar-keting authorization for SHIRE’S VEYVONDI [vonicog alfa, recombinant von Willebrand factor] for the treatment of bleeding events and treatment/prevention of surgical bleeding in adults (age 18 years and older) with von Willebrand disease (VWD) when desmopres-sin (DDAVP) treatment alone is ineffective or not indicated. If marketing authorization is granted by the European Commission, VEYVONDI will become the first and only recombinant von Willebrand factor (rVWF) treatment available in the EU for VWD that specifically addresses the primary deficiency or dysfunction of von Willebrand factor (VWF), while also allowing the body to restore and maintain adequate endogenous factor VIII plasma levels.

The CHMP submission was based on outcomes from three clinical trials involving a total of 80 patients with VWD, including a Phase 3 multicenter open-label study that assessed the pharmaco-kinetics, safety and efficacy or rVWF:rFVIII and VEYVONDI (rVWF) in the treatment of bleeding episodes in adult subjects with severe VWD.

In the U.S., the product is approved under the trade name VONVENDI [von Willebrand factor (Recombinant)] and indicated for use in adults (age 18 years and older) diagnosed with VWD for on-demand treatment and control of bleeding episodes or perioperative management of bleeding.


JULY 2018

Page 171

BLOOD & BIOTECHNOLOGY

* BIOVERATIV and SANGAMO THERAPEUTICS announced that the U.S. FDA has accepted an Investigational New Drug (IND) application for BIVV003, a gene-edited cell therapy can-didate for the treatment of people with sickle cell disease. Sangamo and Bioverativ, a SANOFI company, are developing BIVV003 as part of an exclusive worldwide collaboration to develop and commercialize gene-edited cell therapies for sickle cell disease and beta thalassemia.

BIVV003 is a non-viral approach that utilizes zinc finger nuclease (ZFN) gene-editing technology to modify a short sequence of the BCL11A gene in red blood cell precursor cells, suppressing sickle hemoglobin production and reactivating the production of potentially protective levels of fetal hemoglobin. Under this IND, Bioverativ plans to initiate a Phase 1/2 clinical trial at several U.S. sites this year to assess the safety, tolerability and efficacy of BIVV003 in adults with sickle cell disease. Meanwhile, Sangamo is currently enrolling patients with transfusion-dependent beta thalassemia in another Phase 1/2 trial evaluating the safety, tolerability and efficacy of ST-400, which utilizes the same gene-editing approach as BIVV-003.

* CRISPR THERAPEUTICS and VERTEX PHARMACEUTICALS announced that the U.S. FDA has placed a clinical hold on the Investigational New Drug Application (IND) for CTX001, an ex vivo CRISPR gene-edited autologous hematopoietic stem cell therapy intended for the treatment of sickle cell disease (SCD). This clinical hold will remain in place pending the resolution of certain questions that will come from the FDA as part of its review of the IND, which was submitted to the agency in April to support the planned initiation of a Phase 1/2 U.S. trial in adult SCD patients.

The planned initiation of a Phase 1/2 trial of CTX001 in Europe in adult patients with transfusion-dependent b-thalassemia is unchanged; the companies expect to initiate this trial in the second half of 2018 (see the January 2018 issue of International Blood/Plasma News). CTX001-edited hematopoietic stem cells produce high levels of fetal hemoglobin (HbF) in red blood cells; HbF is a form of oxygen-carrying hemoglobin that is naturally present at birth, and is then replaced over time by the adult form of hemoglobin. Elevation of HbF by CTX001 could potentially alleviate transfusion requirements for b-thalassemia patients and reduce debilitating sickle crises in persons with SCD.

CRISPR Therapeutics and Vertex entered into a strategic collaboration in 2015, under which Vertex has exclusive rights to license up to six new CRISPR/Cas9-based treatments that emerge from the collaboration, including CTX001. For this particular therapy, the companies will equally share all R & D costs and profits worldwide.

________________________________________________________________________

Published by: The Marketing Research Bureau, Inc. 284 Racebrook Road, Orange, Connecticut 06477 Phone: (203) 799-0298 email: [email protected]

www . marketingresearchbureau.com


JULY 2018

Page 172

* DOVA PHARMACEUTICALS announced that the U.S. FDA has completed its Priority Review and approved DOPTELET (avatrombopag) for the treatment of thrombocytopenia in adult patients with chronic liver disease (CLD) who are scheduled to undergo a proce-dure. DOPTELET is the first thrombopoietin (TPO) receptor agonist approved in the U.S. for this indication.

Two global, multicenter, randomized, double-blind, placebo-controlled Phase 3 trials supported the approval of DOPTELET. In the first study, ADAPT-1, 65.6% of patients who received a 60 mg dose of avatrombopag did not require post-procedural platelet transfusion or rescue procedures for bleeding, compared to 22.9% of placebo patients (P < 0.001); corresponding transfusion-free proportions were 88.1% and 38.2% for patients dosed with 40 mg of avatrom-bopag or placebo, respectively (P < 0.001). The second ADAPT-2 study yielded similar findings.

“DOPTELET is the first orally administered treatment option for patients with CLD, allowing the majority of patients to avoid a platelet transfusion prior to a procedure by increasing platelet counts to the target level of greater or equal to 50,000 per microliter,” said Dova president and chief executive officer Alex Sapir. “Given our extensive preparations to date, we are positioned to launch DOPTELET…with our full complement of sales, marketing and reimbursement support resources,” he added.

There are approximately 70,000 U.S. patients with CLD who have a platelet count of less than 50,000 per microliter, who typically require one to three invasive diagnostic or therapeutic pro-cedures each year, according to the company.

* CELGENE and ACCELERON PHARMA announced that results from their randomized, double-blind Phase 3 MEDALIST trial demonstrated that luspatercept achieved a highly statistically significant improvement in red blood cell (RBC) transfusion independence in patients with low-to-intermediate risk myelodysplastic syndromes (MDS) associated with anemia and frequent RBC transfusion requirements. Luspatercept, a recombinant fusion protein containing a modified extracellular domain (ECD) of the activing receptor type IIB (ActRIIB), is a first-in-class erythroid maturation agent (EMA) that is believed to regulate late-stage RBC maturation.

* Separately, CELGENE and ACCELERON PHARMA announced that administration of

luspatercept in patients with transfusion-dependent beta-thalassemia achieved a highly sta-tistically significant improvement in erythroid response, according to findings from a Phase 3, randomized, double-blind BELIEVE study. An erythroid response was defined as at least a 33% reduction from baseline in RBC transfusion burden compared to placebo, with a reduction of at least two units during the protocol-defined period of 12 consecutive weeks.

Data from both the MEDALIST and BELIEVE studies will be presented at a medical meeting later this year. Other ongoing research sponsored by Celgene and Acceleron is assessing the po-tential of luspatercept to address anemia requiring transfusion in patients with beta-thalassemia and myelofibrosis. The companies plan to submit regulatory applications in the U.S. and Europe in the first half of 2019.


JULY 2018

Page 173

* In the July 2018 issue of Protein Expression and Purification, Chinese investigators at Zhangjiang Institute in Shanghai reported a recombinant human serum albumin (rHSA) yield of nearly 9 grams per liter in a fermenter after 96 hours of methanol induction with the best-performing of a number of tested Pichia pastoris strains.

The codon sequence of human serum albumin (HSA) was cloned under the control of the alcohol oxidase 1 promoter (AOX1) and expressed in Pichia pastoris as a secretory protein. The recombi-nant strain exhibiting the highest HSA yield was selected by screening for resistance to the highest concentration of antibiotic G418.

HSA was purified by filtration and Cibacron Blue affinity chromatography, which yielded a 58% recovery of an albumin product with a >96% purity. “This result is more promising than the previously reports of industrial applications, which reported the highest yield as 92.29 mg/L/hour,” the authors said, noting that the current method doubled the time-space yield.

“This study revealed that Pichia pastoris is an excellent system for recombinant human serum albumin expression,” the authors added. “The high efficiency level of rHSA production lays a solid foundation for its use in industrial production.”

RESEARCH AND DEVELOPMENT

* Intramucosal injection of autologous platelet-rich plasma combined with hyaluronic acid (A-PRP-HA) resulted in a significant increase in the Vaginal Health Index (VHI) and im-provement in clinical symptoms of vaginal dryness and dyspareunia in all 20 treated post-menopausal breast cancer survivors with vulvovaginal atrophy, according to a team of French investigators at the Henri Mondor University Hospital in Créteil. Postmenopausal women with VVA were enrolled if they had a VHI score of <15 and were not candidates for hormone therapy.

At six months following multiple injections of A-PRP-HA into the mucosa and lamina propria of the posterior wall of the vagina (as well as the posterior wall of the introitus), the VHI score increased from a mean pretreatment baseline score of 10.7 ± 2.12 to 20.75 ± 4.8 (P<0.0001). The Female Sexual Distress (FSD) score decreased significantly during the study, from a mean pretreatment baseline score of 36.35± 2.53 to 30.15 ± 2.47 (P<0.0001). No adverse events were reported. A-PRP was prepared using the RegenKit supplied by the Swiss medical device firm REGEN LABS SA.

The investigators concluded that the injection of A-PRP-HA appeared to be a promising method to improve the trophicity and hydration of vaginal mucosa in postmenopausal breast cancer sur-vivors with vulvovaginal atrophy and contraindications to hormone therapy. Complete findings from this study appear in the May 7 online issue of the journal Menopause.


JULY 2018

Page 174

* The privately-held San Francisco area biotechnology company ALKAHEST announced the initiation of a Phase 2 randomized, double-blinded dose response study of GRF6019, an investigational plasma-derived treatment for patients with mild to moderate Alzheimer’s disease. Prepared by Alkahest development partner GRIFOLS, GRF6019 is a proprietary plasma fraction that includes approximately 400 characterized plasma proteins. A total of 40 U.S. patients will be enrolled and randomized to receive either high or low intravenously administered doses of GRF6019 during the study. Subjects will receive daily infusions for five consecutive days during Week 1 and again during Week 13, for a total of 10 doses.

“GRF6019 has demonstrated encouraging preclinical results, including improvements in cognitive and histological measures compared to previously-evaluated whole plasma, and has the potential to address the growing unmet need for an effective treatment for Alzheimer’s disease,” said Alkahest president and CEO Karoly Nikolich.

PRODUCT SAFETY UPDATE

* The U.S. FDA has published a final guidance addressing testing of donor blood for the Zika virus, titled “Revised Recommendations for Reducing the Risk of Zika Virus Transmission by Blood and Blood Components,” which replaces an August 2016 draft guidance. Blood establish-ments are no longer required to conduct universal nucleic acid testing (NAT) on each individual donation; pooled donation NAT is now considered to be adequate. Alternatively for platelets and plasma collected by apheresis, blood establishments can comply by using pathogen reduction technology with an FDA-approved pathogen reduction device; currently CERUS’ INTERCEPT System for platelets and plasma is the sole approved pathogen reduction technology.

This final guidance does not apply to the collection of source plasma, as FDA concluded that current methods of viral inactivation and removal used in manufacturing of therapeutic plasma derivatives are sufficient to acceptably reduce the risk of Zika virus transmission.

* In a poster presentation this month at the 23rd Congress of the European Hematology Association in Stockholm, CERUS reported that both primary efficacy and primary safety endpoints were achieved in the company’s European Phase 3 SPARC study evaluating investigational S-303/glutathione pathogen-inactivated red blood cells (INTERCEPT-treated RBCs) in thalassemia major patients. In this double-blinded non-inferiority study, a total of 81 subjects were randomized to sequential treatment periods of INTERCEPT-treated RBCs and conventional RBCs with crossover to the other treatment upon completion of the first treatment period. Each treatment period consisted of six transfusion episodes over approximately five to six months, with the goal of maintaining patients’ targeted transfusion threshold and a primary efficacy endpoint of RBC hemoglobin consumption over four transfusion episodes in each treatment period.

(continued on page 175)


JULY 2018

Page 175

A total of 81 adult and pediatric patients were transfused. On an intent-to-treat basis, total mean hemoglobin consumption in the evaluation period was 0.113 ± 0.04 g/kg/day in the INTERCEPT arm compared to 0.111 ± 0.04 g/kg/day in the control arm. The mean treat-ment difference of 0.002 g/kg/day (1.8%) was well below the pre-determined 15% inferiority margin (<0.017 g/kg/day). There were no adverse events deemed certain or likely related to INTERCEPT-treated RBCs, and no treatment-emergent antibodies with confirmed specificity to INTERCEPT-treated RBCs or RBC antigens.

* GRIFOLS has received U.S. FDA approval to market two blood screening assays: Procleix Ultrio Elite and Procleix WNV. The Procleix Ultrio Elite assay simultaneously screens for human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV) and hepatitis B virus (HBV), as well as detecting HIV type 2 (HIV-2). This assay can also be used to test pools of up to 96 individual donations of source plasma. The Procleix WNV assay is a highly sensitive, qualita-tive in vitro nucleic acid assay for the detection of West Nile virus RNA in plasma and serum of human blood donors.

Both assays will run on the fully automated nucleic acid testing (NAT) blood screening plat-form Procleix Panther system. This integrated NAT system fully automates all steps to perform Procleix assays, from sample testing through amplification, detection and data reduction. The Procleix Panther system received CE Mark and launched in Europe in 2012. In June 2016 the FDA allowed blood centers to employ this platform with Grifols’ Procleix Zika virus assay under an Investigational New Drug (IND) study protocol to screen donated blood nationwide. Grifols plans to begin commercializing the Procleix Ultrio Elite and Procleix WNV assays later this year.

PEOPLE

* HAEMONETICS has appointed Said Bolorforosh, PhD to the newly created position of execu-tive vice president and chief technology officer, and will report to CEO Chris Simon. In this role, Dr. Bolorforosh will lead the company’s innovation agenda and oversee research, development and medical and clinical affairs. He will also be responsible for “developing technical capabilities and optimizing product and technology investments to drive accelerated growth,” according to a Haemonetics news release.

Prior to joining Haemonetics, Dr. Bolorforosh was president, Ultrasound, at Siemens Healthcare. He previously served as vice president and general manager of Intensive Insulin Delivery, vice president of R&D and chief technology officer for Medtronic’s Diabetes division. From 2004 to 2014, he held positions of increasing responsibility at General Electric’s Ultrasound division. He received a Bachelor Science in Electronic and Electrical Engineering from Cardiff University, University of Wales, and a doctorate in Electronic Engineering from University of London, King’s College London.


JULY 2018

Page 176

* RUBIUS THERAPEUTICS has appointed Pablo J. Cagnoni, MD as its new chief executive officer. He will partner with Rubius president Torben Straight Nissen to advance the company’s Red Cell Therapeutics product pipeline. Dr. Cagnoni most recently served as president and CEO of Tizona Therapeutics, a privately held biotechnology firm focused on development of novel treatments for cancers. Previously he served as president of Onyx Pharmaceuticals, global head of clinical development at Novartis Oncology and chief medical officer at Allos Therapeutics and OSI Pharmaceuticals.

NEW PRODUCTS

* The JEFFREY MODELL FOUNDATION (JMF) announced that, after conducting a multi-year study, it is set to launch an upgraded version of its SPIRIT ANALYZER software, for use by hospital networks and major healthcare organizations to screen patients for potential undiagnosed primary immunodeficiency disorders (PI). The SPIRIT 3.0 Analyzer (Software for Primary Immunodeficiency Recognition, Intervention and Tracking) matches 352 ICD-10 di-agnosis codes to JMF’s 10 Warning Signs of PI to identify at-risk patients. It is easy to download, compliant with all applicable regulations, and has the capacity to screen up to one million patient records within 30 minutes, according to a JMF news release.

The new SPIRIT ANALYZER software will be accessible and distributed to medical providers and healthcare insurance companies as a public service by JMF. Early detection and treatment of PI can yield significant reductions in acute and chronic infections, pneumonias, hospital and emergency room visits, days on antibiotics, days in the hospital and missed school/work days. A study sponsored by JMF concluded that more than $42 billion is spent annually in the U.S. to provide healthcare for preventable illnesses in undiagnosed persons with PI.

* The U.S. FDA has granted 510(k) marketing clearance for ARTHREX’ (Naples, FL) Thrombinator System for use with the Arthrex Angel concentrated Platelet Rich Plasma (cPRP) System. Comprising a sterile, single-use device and a separate filter, the Thrombinator System is used to prepare autologous thrombin serum from anticoagulated peripheral blood (or platelet poor plasma) that is to be mixed with platelet rich plasma – rapidly prepared from whole blood or a small mixture of blood and bone marrow using the Arthrex Angel cPRP System – and autograft or allograft bone prior to application to a bony defect.

To demonstrate product performance, Arthrex has conducted clot time, thrombin concentration and bone graft hardness testing and compared the results to a predicate device; the Thrombinator System for use with the Arthrex Angel concentrated cPRP System passed all performance testing criteria. For more information, please visit www . arthrex.com and search on “Arthrex Angel System.”

Products and services for hemostasis research • Purified blood coagulation factors • Antibodies• Factor deficient plasmas• Customized blood collection tubes• R&D assay services

HTI is a manufacturer of highly-purified, native plasma proteins and associated products involved in the hemostatic system. Development of assays for research or destined for cGMP testing is also offered.

Testing and services for protein biotherapeutics• Thrombin generation assays• Analytical testing for IVIG products• Immunogenicity testing• Stability & release testing• Host cell protein mitigation

HBS is a cGMP-certified, QC testing laboratory that specializes in providing services for protein biotherapeutics manufacturers from drug inception through market release.

haemtech.com haemtechbiopharma.com

One Company

Two Solutions


JULY 2018

Page 177

RECENT U. S. PATENTS

* Monoclonal Antibodies Against Antithrombin b. #9,908,942. Assigned to Bayer Healthcare LLC (Whippany, NJ). A monoclonal antibody capable of binding the antithrombin b heparin complex (ATH).

* Antibodies That Bind Urokinase Plasminogen Activator. #9,908,944. Assigned to Novo Nordisk A/S (Bagsvaerd, Denmark). An antibody or antigen-binding fragment thereof that is capable of binding to human uPA.

* Fluidic Device for Producing Platelets. #9,909,102. Assigned to Platod (Paris, France) and Ecole Supérieure de Physique et de Chimie Industrielles de la Ville de Paris (Paris, France). A fluidic device for producing platelets from a suspension of megakaryocytes, comprising:

a) a production chamber comprising b) at least one channel delimited by non-porous walls, c) at least one inlet opening at one end in which a suspension of cells comprising megakary-

ocytes can be introduced and d) at least one outlet opening at the other end, in which platelets can be collected; wherein at least one portion of the inner surface of the walls of said channel is textured with a plurality of obstacles.

* Variant Factor VIII Polypeptides and Methods of Their Production and Use. #9,914,764. Assigned to Bayer Healthcare LLC (Whippany, NJ). A variant of a Factor VIII polypeptide, wherein said Factor VIII polypeptide is a functional Factor VIII comprising a thrombin cleav-age site at amino acid positions 370-375 and an activation loop at amino acid positions 558-565, wherein said amino acid position numbering is with reference to the amino acid sequence set forth in SEQ ID NO: 1; and wherein said variant comprises amino acid substitutions within the thrombin cleavage site as characterized in the patent.

* Cross-Reactive Staphylococcus Aureus Antibody. #9,914,767. Assigned to Arsanis Biosciences GmbH (Vienna, Austria). A recombinant monoclonal cross-neutralizing antibody composition comprising at least one polyspecific binding site that binds to alpha-toxin (Hla) and at least one of a bi-component toxin of Staphylococcus aureus wherein the antibody has an affinity to bind each of said Hla and said at least one of a bi-component toxin with a Kd of less than 10−9M.

* FVII Polypeptide Variants Exhibiting Altered Interaction With Endothelial Protein C Receptor and Methods of Use Thereof for Modulating Hemostasis. #9,914,918. Assigned to The Children’s Hospital of Philadelphia (Philadelphia, PA). An isolated human Factor VII (FVII) variant having 1-2 amino acid substitutions in its Gla domain.


JULY 2018

Page 178

* Preparation of Recombinant Human Plasma Phospholipid Transfer Protein (PLTP) from the Milk of Transgenic Rabbits. #9,920,103. Assigned to Bioprotein Technologies SA (Lyon, France) and Institut National de la Sante et de la Recherche Medicale (INSERM) (Paris, France). A method of A method of producing an active recombinant human plasma phospholipid transfer protein (PLTP) preparation, said method comprising:

(i) harvesting milk produced by a transgenic rabbit secreting active human PLTP in its milk,

(ii) precipitating casein in the harvested milk in the presence of EDTA at acidic pH of less than or equal to 4.6,

(iii) clarifying the product obtained in (ii) and recovering the whey, and (iv) extracting the PLTP from the whey to form the PLTP preparation;wherein the PLTP preparation has a phospholipid transfer activity at least 50 times higher than in untreated milk produced by a transgenic animal that secreted active human PLTP in its milk.

* Single Domain Serum Albumin Binding Protein. #9,920,115. Assigned to Harpoon Therapeutics, Inc. (South San Francisco, CA). A composition comprising a single domain serum albumin binding protein, comprising complementarity determining regions CDR1, CDR2, and CDR3.

* Compositions and Methods to Enhance the Immune System. #9,920,122. Assigned to Stichting Sanquin Bloedvoorziening (Amsterdam, Netherlands). A composition comprising:

(i) a therapeutic compound that can trigger a host’s immune effector cells against a cancer cell, wherein said therapeutic compound is a therapeutic antibody comprising a human or non-human primate IgG Fc portion, wherein the therapeutic antibody induces antibody-dependent cellular cytotoxicity (ADCC), and

(ii) at least one agent capable of reducing or preventing inhibitory signal transduction initiated via SIRPα, wherein said agent is an anti-SIRPα antibody or a Fab fragment, a F(ab′)2 fragment or a scFv fragment thereof.

* Synthetic Antiserum for Rapid-Turnaround Therapies. #9,920,128. Assigned to The Johns Hopkins University (Baltimore, MD). A method for synthesizing an antiserum for rapid-turnaround therapies, including collecting antibody-secreting cells from a test subject who has been exposed to a target biological agent and has produced a successful antibody response; generating variable-region-coding DNA sequences from the antibodies that neutralize the target biological agent, and tagging amplicons of the variable-region-coding DNA sequences with unique nucleic acid identi-fiers to associate the variable-region-coding DNA sequences derived from individual ones of the subset of the antibody-secreting cells; analyzing antibody-type distribution in a natural immune response, synthesizing antibodies from the variable-region-coding DNA sequences to form syn-thetic antibodies; and mixing the synthetic antibodies in a proportion equal to the antibody-type distribution in the natural immune response to form the antiserum.


JULY 2018

Page 179

* Process for Producing and Purifying Factor VIII and Its Derivatives. #9,926,361. Assigned to SK Chemicals Co., Ltd. (Gyeonggi-Do, South Korea). A method for reducing factor VIII-cleaving activities of proteases released during cell cultivation and for increasing homogeneity of recombinant factor VIII, wherein said recombinant factor VIII is produced from mammalian host cells transformed with an expression DNA vector containing cDNA coding for FVIII or FVIII derivatives in a culture medium, and said recombinant factor VIII is purified using factor VIII specific affinity molecules linked to a solid support, said method comprising:

(a) culturing said mammalian host cells in a culture medium, which is supplemented with dextran sulfate having an average molecular weight of 20 to 5,000 kDa;

(b) concentrating said culture medium containing recombinant factor VIII through ultrafiltra-tion; and

(c) purifying said factor VIII from the concentrated culture medium by an immunological method;

wherein said recombinant factor VIII is dBN(64-53); andwherein said factor VIII-cleaving activities of proteases released during cell cultivation are reduced and homogeneity of said recombinant factor VIII is increased.

* Chromatographic Process for Producing High Purity Fibrinogen and Thrombin. #9,932,388. Assigned to Hemarus Therapeutics Limited (Hyderabad, India). A chromatographic process for the isolation and purification of fibrinogen and thrombin, obtained from human plasma, without the use of ethanol precipitation, that contains plasminogen in amounts less than 1 ug/mL, comprising:

(a) subjecting said human plasma to gel filtration chromatography to obtain three fractions (Fraction I, Fraction II and Fraction III);

(b) subjecting Fraction II and Fraction III to additional chromatography steps for purification; and

(c) subjecting to viral inactivation and recovering isolated purified fibrinogen from Fraction II and recovering isolated purified thrombin from Fraction III.

* Process for Production of Fibrinogen. #9,938,318. Assigned to Octapharma AG (Lachen, Switzerland). A fibrinogen product having fibronectin content of 0.01-1.00 μg per mg Fibrinogen-Clauss (F-C), obtainable by a process that includes:

a) solubilization of cryoprecipitate, solubilized at about neutral pH;b) subjecting the solution to adsorption with Al(OH)3 and removing a resulting gel;c) virus inactivating the resulting solution of step b) by a solvent/detergent (S/D) treatment with Triton and TnBP, extraction of S/D reagents with vegetable oil and contacting the water-phase with a TMAE resin at defined pH-value and osmolality;d) precipitation of F-C and separation of a F-C paste;e) resuspension of the F-C paste in TRIS buffer at a pH of about 8.0, and filtration;f) loading the filtered solution of step e) onto a strong anion exchange resin and washing off loosely bound substances with a wash buffer of ~12.0 mS/cm conductivity;g) elution of F-C with an elution buffer containing ~1.5 g/l sodium citrate, ~7.0 g/l NaCl and about 10.0 g/l glycine, adjusted to specified pH and conductivity; andh) concentrating, formulating, sterile filtering and filling into containers.


JULY 2018

Page 180

MEETINGS

SUBSCRIPTION FORM

Please enter my subscription to International Blood/Plasma News for the next 12 issues:

❑ North America $425 * ❑ Other Countries $450 * (airmail)

❑ Payment Enclosed/follows ❑ Please bill me

❑ Mastercard or Eurocard ❑ American Express ❑ Visa

Card Number: ________________________________________Exp. Date:_________________________

Signature:__________________________________________________CVC_______________________

Name: _________________________________________Title:___________________________________

Company/Organization: __________________________________________________________________

Address: ______________________________________________________________________________

City:__________________________________State:________Zip Code:__________________________

Country: ______________________________________________________________________________

Telephone: _________________________________Fax________________________________________

Email: ________________________________________________Date____________________________

* Individual subscription rates only. For corporate subscription rates, please inquire with the Marketing Research Bureau, Inc.284 Racebrook Road, Orange, CT 06477 USA. Tel: +1-203-799-0298; email [email protected] issues: $45 per issue. Wire transfers to Bank of America, Orange, Connecticut 06477, account number, routing number and swift code will be provided upon request. Tax ID Number: 06-142-3668

September 5-7, 2018Parenteral Drug Industry CongressPlasma Protein Summit BeijingBeijing International HotelBeijing, ChinaPhone: +86 10 582 560 86Email: [email protected]: www.pdichina.org/

September 13-16, 201837th World Congress of the International Society of HematologyVancouver Convention CentreVancouver BC, CanadaPhone: 604 681 2153Website: www.ish2018.com

October 5-7, 2018 European Hemophilia Consortium (EHC) ConferenceThe Hotel BrusselsBrussels, BelgiumPhone: +32 2 893 2470Email: [email protected]: https://www.ehc.eu/

October 11-13, 201870th Annual Meeting National Hemophilia FoundationOrlando World Center MarriottOrlando, FLPhone: 212-328-3700Email: [email protected]: www.hemophilia.org

October 13-16, 2018Annual AABB CongressBoston Convention & Exhibition CenterBoston, MAPhone: 301-907-6977Website: www.aabb.org

November 12-15, 2018Third International BioProcessing Asia ConferenceLangkawi International Convention CenterLangkawi , MalaysiaEmail: [email protected]: www.bioprocessingasia.net

Documents

VOLUME 35 ISSUE 12 JULY 2018 - Marketing Research Bureau€¦ · * Reflecting strong global demand for human polyvalent immunoglobulin products, HAEMONETICS reported 10.6% growth