Download Lipsovir

Medivir develops a new unique treatment
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.
aciclovir
patent protection
hydrocortisone
formulation
The Lipsovir concept is a completely new way of
managing the life long infection of the cold sore virus
Avoid your next cold sore
Ow!
IMMUNE RESPONSE
Ow!
Current drugs
IMMUNE RESPONSE
Ow!
Lipsovir
IMMUNE RESPONSE
Drug treatment
Prevents development
of ulderative lesions
Reduction of healing
time
Aciclovir1
No
10-12%
Penciclovir2
No
13-15%
Docosanol (Abreva)3
No
15%
Valaciclovir4
No
10-11%
Lipsovir5
Yes
43%6
Topical treatment
Oral treatment
1 Spruance et al. Antimicrob Agents Chemother 2002
2 Spruance et al. JAMA 1997
3 Sacks et al. J Am Acad Dermatol 2001
4 Spruance et al. Antimicrob Agents Chemother 2003
5 Evans et al. Antimicrob Agents Chemother 2002
6 Combined effect of prevention of lesions and reduction of healing time
Avoid your next cold sore
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
An effective pharmaceutical like Lipsovir is
expected to expand this market
Avoid your next cold sore
US market labial herpes (million USD)
Abreva (GSK)
50
Denavir
(Novartis) 20
Zovirax cream
+ ointment
(Biovail) 90
Other oral
antivirals 20
Valtrex (GSK)
203
NB! Only 1-2% of all cold sore
episodes are currently treated
Total USD 383 miljon, current growth 17% (IMS)
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
Avoid your next cold sore
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,
Avoid your next cold sore
FDA’s Office of Generic Drugs
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 These
number results
of cold sores was 36% lower in those receiving
support the
phase
II than in the other group (p=0.09,
famciclovir
+ steroid
cream
dvs trend)trails
o Preclinical data3 show that Lipsovir gives a 50% better therapeutic
efficacy than acyclovir cream alone
1) Evans et al, Antimicrobial Agents & Chemotherapy 2002
2) Journal of Infectious Diseases 2000
3) Harmenberg et al, Antiviral Chemistry & Chemotherapy 2003
Avoid your next cold sore
Drug
Year
Chief
Investigator
Type of
study
Treatment start
Primary endpoint
Penciclovir
cream
19931994
Spruance
Field
study*
< 1 hour after first
symptom
Time to healing
Zovirax cream
(acyclovir)
19971998
Spruance
Fieldstudy*
< 1 hour after first
symptom
Episode duration
Valtrex
(valaciclovir)
20002001
Spruance
Fieldstudy*
Directly upon first
symptom
1.Episode duration
2. Number of
patients who
develop cold sores
Lipsovir
20062007
Hull/Spruance
Field
study*
<1 hour after first
symptom
Number of patients
who develop cold
sores
* Field study:
1) Patients are given clinical trial material
2) Patients self-initiates treatment as soon as they feel the
symptoms of a cold sore episode
Avoid your next cold sore
o A pharmaceutical with two active ingredients must usually show
therapeutic superiority over
o Each active ingredient on their own
o Placebo
o Issues which have been discussed with authorities:
o Can we avoid the hydrocortisone-alone comparison? Yes
o Which is the most relevant acyclovir cream for the trial?
Same cream base
o Is it sufficient with one pivotal trial? Yes!
as Lipsovir
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
Avid your next cold sore
The purpose of the study is to show that Lipsovir
prevents development of ulcerative lesions
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).
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
A handful of
experienced
consultants in close
collaboration
with Medivir
Scientific Board
CRO companies in USA
Clinical centres in USA and Canada
CRO för
Phase III trails
1 project manager
1 project assistant
6 monitors
medical advisor
data management
statistician
safety monitoring
report drafting
Manufacturor
1 project manager
manufacturing
personnel
analytical chemists
quality assurance
Clinical trial
packaging
1 project manager
quality assurance
programmers
Undvik Avoid your next cold s
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
July
Rectruitment of > 2000 patients
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 sores
o 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
recruitment
Patient
receives
their tube
Waiting...
It can take months
symptoms
5 days treatment
Clinic visits until symptom-free
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
Avoid your next cold sore
Medivir develops a new unique treatment
Lipsovir cream can prevent the development of a cold sore
No other drug treatment has shown this effect
Avoid your next cold sore