Vertex
Will Study All-Oral Regimen of HCV Protease Inhibitor Telaprevir
plus Polymerase Inhibitor VX-222
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| SUMMARY:
Vertex Pharmaceuticals announced this week that the
company will test its lead hepatitis C virus (HCV) protease
inhibitor, telaprevir,
in combination with its investigational HCV polymerase
inhibitor VX-222. The dual oral regimen will be evaluated
both on its own and with the current standard therapy,
pegylated interferon
plus ribavirin. |
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With the most advanced directly targeted oral hepatitis C drugs
now in Phase 3 trials, investigators have begun to look at all-oral
combination regimens, which are expected to slow emergence of
resistance and could potentially allow people with hepatitis C
to avoid the side effects of pegylated interferon and ribavirin.
Roche/Genentech
was the first to test such a combination, the HCV
protease inhibitor RG7227 (also known as ITMN-191) plus the
polymerase inhibitor RG7128; the first results from the INFORM-1
trial were presented this past fall. The Abbott/Enantta collaboration
also announced this week that it will begin a Phase 2 trial testing
3 new agents, the investigational protease inhibitor ABT-450 and
the polymerase inhibitors ABT-333 and ABT-072. Each agent will
be studied in combination with standard therapy now, but they
offer the potential for all-oral regimens in the future.
Below
is an excerpt from the recent Vertex press release announcing
their pending trial.
Vertex Broadens its Commitment to Improving
HCV Care with Clinical Trial to Evaluate Combination Regimens
Based on Oral Antiviral Therapies
 |
Trial
will evaluate safety and SVR rates with multiple 12-week response-guided
regimens of telaprevir/VX-222-based combination therapy, including
two-drug regimens of telaprevir and VX-222 |
|
Interim
clinical data expected in the second half of 2010 |
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Multiple
clinical trial sites in the U.S. to enroll patients |
Cambridge,
Mass. -- March 1, 2010 -- Vertex Pharmaceuticals Incorporated
(Nasdaq: VRTX) today announced that it is initiating the first
clinical trial evaluating Vertex's lead investigational hepatitis
C virus (HCV) protease inhibitor, telaprevir, dosed in combination
with the company's lead investigational HCV polymerase inhibitor,
VX-222. This Phase 2 trial will evaluate sustained viral response
rates (SVR; defined as undetectable HCV RNA 24 weeks after the
end of treatment) using multiple 12-week response-guided regimens
of telaprevir/VX-222-based combination therapy, including two-drug
regimens that contain only telaprevir and VX-222. The trial is
expected to enroll approximately 100 treatment-naive genotype
1 HCV patients at multiple clinical trial sites, the majority
of which will be located in the U.S. Enrollment is expected to
be completed in the second quarter of 2010. Vertex expects to
obtain interim clinical data, including safety and viral kinetic
data, from this trial in the second half of 2010.
"Vertex is committed to improving patient care in HCV, and
the announcement of this clinical trial combining two oral agents,
telaprevir and VX-222, signifies our first exploration into this
combination regimen's potential role to further improve the treatment
of HCV," said Peter Mueller, PhD, Vertex's Chief Scientific
Officer and Executive Vice President, Global Research and Development.
"The completion of the Phase 3 development program for telaprevir
remains our primary focus, and we are on track to submit a New
Drug Application for telaprevir in the second half of 2010. We
believe telaprevir could represent a significant opportunity to
improve the treatment of HCV, and simultaneously, we are focused
on evaluating additional opportunities to potentially enhance
HCV therapy even more in the years ahead using novel combination
regimens based on oral antiviral agents. We believe the trial
announced today will inform the development path for telaprevir/VX-222-based
combination therapy, and we look forward to obtaining the first
clinical data from the trial later this year," continued
Dr. Mueller.
About the Phase 2 Trial of Telaprevir
and VX-222
The randomized, parallel-group, dose-ranging trial announced today
is designed to evaluate the safety and antiviral activity, including
SVR, of multiple 12-week response-guided telaprevir/VX-222-based
combination regimens. The primary endpoint of this trial is to
assess safety and tolerability of telaprevir/VX-222-based combination
therapy. A secondary endpoint of this study is to assess the proportion
of patients in each study arm who achieve SVR. The trial is expected
to enroll approximately 100 treatment-naïve genotype 1 HCV
patients at approximately 20 clinical trial sites, predominantly
in the U.S. Vertex expects to complete enrollment for the trial
in the second quarter of 2010. The trial will consist of four
arms, as noted below:
|
12-Week
Treatment Regimens
|
Patient
Enrollment
|
| Telaprevir
(1125 mg BID) + VX-222 (100 mg BID) |
25
|
| Telaprevir
(1125 mg BID) + VX-222 (400 mg BID) |
25
|
| Telaprevir
(1125 mg BID) + VX-222 (100 mg BID) + peg-IFN + RBV |
25
|
| Telaprevir
(1125 mg BID) + VX-222 (400 mg BID) + peg-IFN + RBV |
25
|
| BID
= twice daily, peg-IFN = pegylated interferon, RBV = ribavirin
|
Response-Guided
Trial Design
The trial will utilize response-guided criteria aimed at evaluating
shorter-duration treatment regimens. All patients, regardless
of treatment group, whose HCV RNA levels are undetectable (<10
IU/mL) at week 2 and week 8 of treatment, will stop their assigned
treatment at week 12. Patients who do not meet these criteria
will complete their assigned treatment and at week 12, those in
the dual-drug regimen will receive follow-on therapy of 24 weeks
of pegylated-interferon (peg-IFN) and ribavirin (RBV), for a total
of 36 weeks of treatment. Patients in the quad-therapy regimens
who do not meet these criteria at week 12 will receive an additional
12 weeks of follow-on therapy with peg-IFN and RBV for a total
of 24 weeks of peg-IFN and RBV therapy.
Potential Additional Arms of Telaprevir/VX-222-based Combination
Treatment
Based on an evaluation of on-treatment safety, pharmacokinetic
and antiviral data from patients in each arm of the trial, Vertex
may elect to enroll up to two additional treatment arms that will
evaluate telaprevir/VX-222-based combination therapy. The components
of the treatment regimens of these arms will be selected based
on clinical data that emerges from the four initially studied
regimens. If enacted, up to 25 patients are expected to enroll
in each additional treatment arm.
Recent Clinical Trials Support Evaluation
of Telaprevir/VX-222-based Combination Regimens
Phase 1b/2a Clinical Trial of VX-222 in HCV Patients
Interim clinical results from a two-part Phase 1b/2a clinical
trial of VX-222 showed that in the multiple-dose Phase 1b viral
kinetic portion of the trial (Part A), VX-222 was well-tolerated
across four VX-222 dose groups with no serious adverse events
reported. Part A enrolled 32 genotype 1 HCV patients to receive
three days of dosing, and a mean HCV RNA decline of greater than
3 log10 was observed across all four VX-222 dose groups. An increasing
dose response was observed across the four dose groups, with the
results with 500 mg and 750 mg BID, and 1500 mg QD (once-daily)
being very similar. The mean HCV RNA decline achieved after three
days of dosing with 250 mg, 500 mg, and 750 mg of VX-222 every
12 hours (q12h) was 3.1 log10, 3.4 log10, and 3.2 log10, respectively.
Additionally, the mean HCV RNA decline achieved after three days
of dosing with 1500 mg of VX-222 every 24 hours (QD) was 3.4 log10.
For patients who received placebo, the mean HCV RNA decline after
three days of dosing was 0.1 log10. The majority of the patients
enrolled in Part A had genotype 1a chronic HCV infection. Full
results including the final safety analysis from Part A of this
trial are expected to be presented at a medical meeting in 2010.
The interim results of Part A of this trial are consistent with
the findings from a previously conducted three-day, five-patient
viral kinetic study of VX-222. Part B of the study, which will
be initiated shortly will evaluate 12 weeks of VX-222 dosed in
combination with peg-IFN and RBV in treatment-naïve HCV patients.
Drug-Drug Interaction Study of Telaprevir and VX-222 in Healthy
Volunteers
Vertex also recently completed a Phase 1 study of telaprevir and
VX-222 designed to evaluate the safety, tolerability and drug-drug
interaction of telaprevir and VX-222 in approximately 20 healthy
volunteers. In the study, the 10-day telaprevir/VX-222-based combination
regimens were well-tolerated with no serious adverse events reported.
In this study, an increase in the plasma exposure of VX-222 was
observed when dosed in combination with telaprevir, while the
plasma exposure of telaprevir was not affected when dosed in combination
with VX-222. Based on this observation, Vertex selected VX-222
doses of 100 mg twice-daily BID and 400 mg BID for evaluation
in the Phase 2 trial of telaprevir/VX-222-based combination therapy
announced today. The VX-222 doses of 100 mg BID and 400 mg BID
are expected to provide plasma exposures similar to those observed
with doses of 250 mg BID and 750 mg BID, respectively, in the
previously conducted viral kinetic studies of VX-222 monotherapy
in HCV patients.
The results of both the three-day viral kinetic study of VX-222
and the drug-drug interaction study of telaprevir/VX-222-based
regimens support the Phase 2 combination trial of telaprevir and
VX-222 in HCV patients, as announced today.
About Telaprevir and VX-222
Telaprevir is an investigational oral inhibitor of HCV protease,
an enzyme essential for viral replication, and is being evaluated
as part of a global Phase 3 registration program in more than
2,200 treatment-naïve and treatment-failure patients. Vertex
is collaborating with Tibotec and Mitsubishi Tanabe Pharma to
develop telaprevir. Vertex retains commercial rights to telaprevir
in North America. Tibotec has rights to commercialize telaprevir
in Europe, South America, Australia, the Middle East and other
countries. Mitsubishi has rights to commercialize telaprevir in
Japan and certain Far East countries.
VX-222 is an investigational oral non-nucleoside inhibitor of
HCV NS5B polymerase. Vertex added VX-222 to its development pipeline
as part of the acquisition of ViroChem Pharma Inc. in March 2009.
Vertex retains worldwide commercial rights to VX-222.
About Vertex
Vertex
Pharmaceuticals Incorporated is a global biotechnology company
committed to the discovery and development of breakthrough small
molecule drugs for serious diseases. The Company's strategy is
to commercialize its products both independently and in collaboration
with major pharmaceutical companies. Vertex's product pipeline
is focused on viral diseases, cystic fibrosis, inflammation, autoimmune
diseases, epilepsy, cancer, and pain. Vertex co-discovered the
HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
For more information, see www.vrtx.com.
3/5/10
Source
Vertex Pharmaceuticals. Vertex Broadens its Commitment to Improving
HCV Care with Clinical Trial to Evaluate Combination Regimens
Based on Oral Antiviral Therapies. Press release. March 1, 2010.
