to recently presented data from treatment-naive participants
in the PILLAR
trial, these findings indicate that TMC435
appears to work well for patients with or without prior treatment
failure. Further follow-up is underway to see if viral suppression
will be sustained 6 months after completion of therapy (sustained
virological response, or SVR).
is an edited excerpt (including reformatted tables) from a press
release issued by Medivir describing the study and its findings.
Announces Positive 24-week Interim Data of
TMC435 From the ASPIRE Study (C206)
Daily Novel Therapy in Treatment-Experienced Hepatitis C
of the Study -- TMC435 Added to Standard of Care:
the response rates and antiviral efficacy, which progressed?through
to week 24
the number of patients with undetectable hepatitis C virus?(HCV)
levels through week 4, 12 and 24
and well tolerated
Sweden -- November 18, 2010 -- Medivir AB (OMX: MVIR), the emerging
research-based specialty pharmaceutical company focused on infectious
diseases, announces today positive top-line 24-week interim
data from the Phase 2b ASPIRE (C206) study of TMC435 in treatment-experienced
hepatitis C patients. The results demonstrate the potent and
consistent antiviral efficacy of TMC435 in patients who had
failed earlier treatment with peg-IFN [pegyalted interferon]
and ribavirin (standard of care), as well as a safety and adverse
event profile for TMC435 that is consistent with what Medivir
previously reported in the Phase 2b PILLAR C205 study. TMC435,
a hepatitis C protease inhibitor, dosed once daily (q.d.) is
being developed jointly by Tibotec Pharmaceuticals and Medivir.
The ASPIRE study evaluates the effect of TMC435 in combination
with standard of care in 462 patients infected with the difficult
to treat genotype 1 hepatitis C virus who had undergone and
failed prior treatment with standard of care. The study includes
patients that have relapsed, achieved partial response, or achieved
no response (null responders) to treatment with standard of
TMC435 was administered once daily at a dose of either 100 mg
or 150 mg given for either 12, 24, or 48 weeks in combination
with standard of care. Standard of care treatment was continued
until the study completion at week 48.
Overview of the ASPIRE (C206) Week
24 Interim Study Results
The week 24 interim analysis was performed when all patients
completed 24 weeks of treatment or discontinued earlier. An
Intention-to-Treat (ITT) analysis was performed including all
patients who took at least one dose of TMC435.
In the interim analysis, patients treated with TMC435 and standard
of care demonstrated high response rates and antiviral efficacy
in all patient groups up to and including week 4, 12 and 24.
In the relapser group, 81%, 92% and 94% of patients taking TMC435
and Peg-IFN and ribavirin achieved undetectable HCV RNA levels
at week 4, week 12, and week 24, respectively. For the partial
responder group 62%, 84%, and 86% achieved undetectable HCV
RNA levels at week 4, week 12 and week 24, respectively.
The null responder group also demonstrated significant response
rates with 38%, 64%, and 78%, of patients taking TMC435 and
Peg-IFN and ribavirin achieving undetectable HCV RNA levels
at week 4, week 12 and week 24, respectively. All patients continue
on active treatment up until week 48.
Intention-to-Treat Analysis of Virologic
Response: HCV RNA < 25 IU/mL
data pooled and all data are taken into account at the specific
4 - RVR
undetectable at end of trial [end of treatment] (EOT)
but detectable within 24 weeks of follow-up
**Partial response: > 2 log reduction at Week 12 but
not achieving undetectable at EOT
***Null response: < 2 log reduction in HCV RNA at Week
An Intention-to-Treat analysis was performed including all patients
who took at least one dose of TMC435. TMC435 was generally safe
and well tolerated and the results were consistent with the
previously reported phase 2b PILLAR C205 study. Significant
decreases in transaminases (ALT and AST) were observed in all
TMC435 treatment groups. The two most frequently reported adverse
events (AEs) were fatigue and headache, with comparable results
shown from the placebo group.
on the results, Ron Long, CEO of Medivir, said: "We are
extremely encouraged and excited by the pronounced efficacy
and advantageous safety of TMC435 in these difficult-to-treat
patients that are in a great need of new and improved treatment
options. We are now looking forward to the next important development
milestone for TMC435, the start of Phase 3 clinical trials in
treatment-naive patients in early 2011."
Medivir is an emerging research-based specialty pharmaceutical
company focused on the development of high-value treatments
for infectious diseases. Medivir has world-class expertise in
polymerase and protease drug targets and drug development. Medivir
has a strong R&D portfolio and has recently launched its
first product Xerese/Xerclear. Medivir's key pipeline asset,
TMC435, a protease inhibitor, is in phase 2b clinical development
for Hepatitis C and is partnered with Tibotec Pharmaceuticals.
Xerese/Xerclear is an innovative treatment for cold sores, which
has been approved in both the US and Europe. It is partnered
with GSK to be sold OTC in Europe and Russia and with Meda in
North America. Medivir has retained the Rx rights for Xerclear
in Sweden and Finland.
For more information about Medivir, please visit the company's
About TMC435 clinical trial programs
TMC435 is a once daily protease inhibitor jointly developed
by Medivir and Tibotec Pharmaceuticals to treat hepatitis C
virus infections. TMC435 is currently being studied in three
phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215)
in G1 treatment-naive and in G1 patients that failed previous
IFN-based treatment. TMC435 is planned to enter phase 3 studies
PILLAR Study (TMC435-C205)
TMC435-C205 is an ongoing randomized double-blind global phase
2b study in 386 genotype-1 treatment-naive patients. It evaluates
once daily treatment of TMC435 with different doses and durations
given in addition to standard of care treatment, consisting
of ribavirin and pegIFNalpha-2A. Week 24 interim results were
presented as a late-breaker oral presentation at AASLD 61st
Annual Meeting of the American Association for the Study of
Liver Diseases (AASLD) in Boston, MA, USA.
ASPIRE Study (TMC435-C206)
TMC435-C206 is an ongoing randomized double-blind global phase
2b study in 462 genotype-1 treatment-experienced patients. It
evaluates once daily treatment of TMC435 in with different doses
of given in addition to standard of care treatment, consisting
of ribavirin and pegIFNalpha-2A.
DRAGON Study (TMC435-C215)
is an ongoing Japanese phase 2b study in 92 genotype-1 treatment-naive
patients. It evaluates once daily treatment of TMC435 with different
doses and durations given in addition to standard of care treatment,
consisting of ribavirin and pegIFNalpha-2A.
TMC435-C202 is a completed phase 2a study in treatment-naive
genotype 2 to 6 HCV patients. It is a once daily treatment of
TMC435 during seven days, at 200 mg. Subsequently, patients
could continue with SoC treatment consisting of pegylated interferon
and ribavirin upon agreement with the study doctor.
Medivir Announces Positive 24-week Interim Data of TMC435 From
the ASPIRE Study (C206). Press release. November 18. 2010.