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Medivir develops a new unique treatment
Avoid your next cold sore
Lipsovir cream can prevent the development of a cold sore
No other drug treatment has shown this effect
Avoid your next cold sore
The ingredients of Lipsovir have been used safely for decades.
The trick was bringing them together.
The Lipsovir concept is a completely new way ofmanaging the life long infection of the cold sore virus
aciclovir
patent protection
hydrocortisone
formulation
Ow!
HERPES VIRUS
IMMUNE RESPONSE
Ow!
HERPES VIRUS
IMMUNE RESPONSE
Current drugs
Ow!
HERPES VIRUS
IMMUNE RESPONSE
Lipsovir
Avoid your next cold sore
Avoid your next cold sore
An effective pharmaceutical like Lipsovir is expected to expand this market
Avoid your next cold sore
Only about 1-2% of all cold sore episodes are currently treated
Even so this represents an SEK 3 billion market just in the USA
Avoid your next cold sore
Total USD 383 miljon, current growth 17% (IMS)
US market labial herpes (million USD)
Zovirax cream + ointment (Biovail) 90
Valtrex (GSK) 203
Other oral antivirals 20
Denavir (Novartis) 20
Abreva (GSK) 50
NB! Only 1-2% of all cold sore episodes are currently treated
Avoid your next cold sore
o Famvir (famciclovir) tablets from Novartis- Clinical trials on cold sores performed, but no regulatory approval yet - Probably no more effective than other antiviral treatments - Does not prevent development of cold sores
o Transport Pharmaceuticals- developing apparatus which provides high local dosages of acyclovir via a mild electric current- appears only to shorten episode duration (phase II data)
o interceptCS™- thermal treatment of herpes episodes- approved in Canada- large, clumsy and expensive
o Patents protect Lipsovir from generic competition until 2016
o The formulation technology (cream) is patented to 2019 (2020 in USA)
o Uncommonly difficult and time-consuming for competitors to register a Lipsovir-copy
o Systemic drugs – relationship exists between drug concentration in the plasma and therapeutic activity – quick and easy to do bioequivalance studies
o Topical drugs – no relationship between plasma concetration and therapeutic activity – harder to prove that the copy has the same efficacy as the original
o Topical drugs for cold sores – the indication has no surrogate markers – enormous clinical trials are needed to prove that the copy is not worse than the orginal
o “Unusually high regulatory hurdles for topical herpes drugs” Robert W. Pollock, Lachman Consultant Services, f d Acting Deputy Director, FDA’s Office of Generic Drugs
Avoid your next cold sore
1. Lipsovir phase II data showed a unique therapeutic activity
2. The results for antiviral drugs in this kind of clinical trial are predictive for efficacy in phase III
3. Discussions with FDA have evolved an attractive development programme för Lipsovir
Avoid your next cold sore
o All trial participants (n=380) irradiated with UV light on the lips in order to induce a cold sore episode
o Two days later treatment was commenced with either Lipsovir or placebo cream
o Results with antivirals in this type of clinical trial are predictive of efficacy in phase III
Undvik ditt nästa munsår
o In the phase II trial1 (n=380) the number of cold sores in the Lipsovir-group were 29% lower than the placebo group; the difference is statistically significant (p=0.02)
o Independent studies of Spruance et al2 (n=49)o Trail participants treated with
oral famciclovir + steroid cream; or oral famciclovir + placebo cream
o The number of cold sores was 36% lower in those receiving famciclovir + steroid cream than in the other group (p=0.09, dvs trend)
o Preclinical data3 show that Lipsovir gives a 50% better therapeutic efficacy than acyclovir cream alone
Avoid your next cold sore
These results support the phase II
trails
1) Evans et al, Antimicrobial Agents & Chemotherapy 20022) Journal of Infectious Diseases 20003) Harmenberg et al, Antiviral Chemistry & Chemotherapy 2003
Avoid your next cold sore
* Field study:1) Patients are given clinical trial material2) Patients self-initiates treatment as soon as they feel
the symptoms of a cold sore episode
Drug Year
Penciclovircream
1993-1994
Zovirax cream(acyclovir)
1997-1998
Valtrex (valaciclovir)
2000-2001
Lipsovir 2006-2007
Chief Investigator
Type of study
Spruance Field study*
Spruance Field-study*
Spruance Field-study*
Hull/Spruance
Fieldstudy*
Treatment start
< 1 hour after first symptom
< 1 hour after first symptom
Directly upon first symptom
<1 hour after first symptom
Primary endpoint
Time to healing
Episode duration
1.Episode duration2. Number of patients who develop cold sores
Number of patients who develop cold sores
Avid your next cold sore
o A pharmaceutical with two active ingredients must usually show therapeutic superiority over
o Each active ingredient on their owno Placebo
o Issues which have been discussed with authorities:o Can we avoid the hydrocortisone-alone comparison?o Which is the most relevant acyclovir cream for the trial? o Is it sufficient with one pivotal trial?
o An agreement on the phase III programme has been reached at the End-of-Phase II meeting at the FDA
o The programme has been checked with authorities in the EU
Yes
Yes!Same cream base
as Lipsovir
1270 subjects with recurrent cold sores will be treated with one of the following
Lipsovir Aciclovir cream Placebo cream
Treatment is started as soon as the subjects feel the first symptoms of a cold sore (herpes).
The purpose of the study is to show that Lipsovir prevents development of ulcerative lesions
Avoid your next cold sore
Clinical trials begin July 2006
Clinical trials complete Autumn 2007
Application to authorities Spring 2008
Marketing Approval End of 2008
Avoid your next cold sore
Find partn
er(s) f
or mark
eting
CRO companies in USA
Clinical centres in USA and Canada
A handful of experienced consultants in close collaboration with Medivir
Scientific Board
Undvik Avoid your next cold sore
CRO för Phase III trails
1 project manager1 project assistant6 monitorsmedical advisordata managementstatisticiansafety monitoringreport drafting
Manufacturor
1 project managermanufacturing personnelanalytical chemistsquality assurance
Clinical trial packaging
1 project managerquality assuranceprogrammers
Avoid your next cold sore
o Manufacture and packaging of study drug
o Applications to ethical committees and authorities
o Contracting of 50 clinical centres
o Designation of central laboratories for sample analysis
o Drafting and printing of informational material e.g. Patient diaries and trial questionnaires (CRF)
o Investigator meetings with >100 participants (training ahead of the studies)
o Systems for monitoring inclusion rates
Preparations Rectruitment of > 2000 patients July
Avoid your next cold sore
o People with 3 or more herpes episodes per year recruited to selected clinical centres
o The participants are questioned on their cold soreso is the description consistent with herpes?o can the participant feel the early symptoms of a cold sore episode?o is the participant willing to live up to the trial rules?
o Approved participants receive a tube with clinical trial material + a key ring container anc can return home and await their next herpes episode
Waiting...It can take months
5 days treatment
Clinic visits until symptom-free symptomsrecruitment
Patientreceives their tube
Treatment commences
within an hour
Avoid your next cold sore
o An open study on 100 teenagers (12-17 years) starts in Sweden this autumn
o The aim is to get approval to treat all patients over 12 years
o Only recording of potential side effects
o A study of 75 immunocompromised subjects starts in Russia/Ukraine this autumn
o The aim is to see if the therapeutic efficacy is any different in this patient group
o Both studies performed by av CRO-companies
Medivir develops a new unique treatment
Avoid your next cold sore
Lipsovir cream can prevent the development of a cold sore
No other drug treatment has shown this effect
