Vertex,
InterMune, and Idenix Present Hepatitis C Drug Development Updates
at Investor Conference
 |
 |
 |
 |
 |
 |
 |
| SUMMARY:
At the 28th Annual J.P. Morgan Healthcare Conference,
which took place January 11-14 in San Francisco, pharmaceutical
and biotechnology companies presented updated information
about their clinical development portfolios to potential
investors. Among the presenters were 3 companies with
directly targeted oral HCV drugs in the pipeline: Vertex
Pharmaceuticals (telaprevir,
VX-222), InterMune Inc. (RG7227
[formerly known as ITMN-191], RG7128),
and Idenix Pharmaceuticals (IDX184,
IDX375, IDX320). |
|
 |
 |
 |
 |
 |
 |
 |
Below
are edited excerpts from company press releases describing the
latest hepatitis C developments. Given that these presentations
were aimed at investors, information may be slanted so as to highlight
its financial implications.
Clinical
trial data for promising agents is expected to be presented by
researchers at upcoming medical conferences in the field, including
the annual meeting of the European Association for the Study of
the Liver (EASL 2010) in April, the Digestive Disease Week (DDW
2010) conference in May, and the American Association for the
Study of Liver Diseases' Liver Meeting (AASLD 2010) in late October.
Vertex
Plans to Seek Approval of Telaprevir in Second Half of 2010
Matthew Emmens, Chairman, President and Chief Executive Officer
of Vertex: "Phase 3 data for telaprevir, our lead drug candidate
for the treatment of hepatitis C virus infection, will begin to
emerge in the spring of 2010 to support the planned submission
of a New Drug Application in the second half of this year. Our
more than decade-long commitment to improving patient care in
HCV is unwavering, and the Phase 3 program for telaprevir will
remain our primary focus over the coming year. Importantly, we
also recognize the need for continued innovation in the treatment
of this disease, and we are preparing to initiate the first clinical
trial combining telaprevir with the investigational HCV polymerase
inhibitor VX-222 this quarter."
The hepatitis C program is part of a larger effort to become "a
fully-capable biopharmaceutical company," and Vertex is currently
working on or planning clinical trials for therapies for cystic
fibrosis, rheumatoid arthritis, and epilepsy.
Phase
3 Registration Program for Telaprevir Nears Completion
Sustained viral response (SVR) data expected from Phase 3 ADVANCE
trial in second quarter 2010 and from Phase 3 ILLUMINATE &
REALIZE trials in third quarter 2010
 |
The
ADVANCE, ILLUMINATE and REALIZE trials are evaluating telaprevir-based
regimens as part of a global Phase 3 registration program
in more than 2,200 genotype 1 treatment-naive and treatment-failure
patients with HCV infection. |
|
Vertex
today announced that all patients in the ADVANCE and ILLUMINATE
trials, which are evaluating telaprevir in treatment-naive
patients, have completed dosing of all study drugs, including
pegylated-interferon (peg-IFN) and ribavirin (RBV), and are
now in the post-treatment follow-up period to determine the
number of patients who achieve SVR (defined as undetectable
HCV RNA 24 weeks after the end of treatment). Vertex expects
SVR data to become available from ADVANCE in the second quarter
of 2010 and from ILLUMINATE in the third quarter of 2010. |
|
Vertex
today also announced that all patients in the REALIZE trial,
which is being conducted by Vertex's collaborator Tibotec
and is evaluating telaprevir in patients who did not achieve
SVR with a prior pegylated interferon-based treatment, are
expected to complete dosing of all study drugs, including
pegylated-interferon and ribavirin, by the end of January.
Vertex expects SVR data to become available from REALIZE in
the third quarter of 2010. |
|
Vertex
plans to submit a New Drug Application (NDA) for telaprevir
in the second half of 2010 for both treatment-naive and treatment-failure
patients.
|
Potential
Future Combination Regimens for HCV with Telaprevir and the HCV
Polymerase Inhibitor VX-222
|
Vertex
recently completed a multiple-dose Phase 1b viral kinetic
study of the investigational oral HCV polymerase inhibitor
VX-222. Interim results from the trial are consistent with
the findings of a previously-conducted three-day viral kinetic
study and support future clinical evaluation of VX-222, including
the initiation of the first clinical trial of VX-222 in combination
with telaprevir. Additional results from this Phase 1b study
of VX-222 are planned for presentation at a medical meeting
in 2010. |
|
Upon
completion of ongoing discussions with regulatory authorities,
Vertex plans to initiate a combination trial of telaprevir
and VX-222 in the first quarter of 2010. This trial is expected
to evaluate SVR rates using multiple regimens of telaprevir/VX-222-based
therapy in HCV patients. |
The
full press release is available online.
For more information about Vertex.
InterMune
Provides 2010 Milestones for RG7227 (ITMN-191)
Dan Welch, Chairman, Chief Executive Officer and President of
InterMune: "Today we reported preliminary, top-line results
from two cohorts of the Phase 1b, 15-day study of low-dose RG7227
co-administered with low-dose ritonavir and standard of care (SOC)
in patients with chronic HCV. The majority of patients given ritonavir
with 100 mg RG7227 twice-daily or 200 mg RG7227 once-daily were
HCV RNA negative at the end of therapy. The ritonavir-boosted
regimen provided a more favorable pharmacokinetic profile than
what has been previously observed for 900mg RG7227 administered
twice-daily with SOC but without ritonavir. In view of these data,
our plan is that the development of RG7227 will be in combination
with ritonavir."
(RG7227):
Clinical Development Highlights and Recent Events
Enrollment began in August 2009 of the company's Phase 2b study
of RG7227 in combination with Pegasys) (pegylated interferon alfa-2a)
and Copegus (ribavirin), one of the options for the current standard
of care (SOC) in HCV. The Phase 2b trial was designed to study
both twice-daily (600mg and 900mg q12h) and three-times-daily
regimens (300mg q8h) and both 12-week and 24-week treatment durations.
On November 17, 2009, InterMune announced that three patients
in the blinded 900mg q12h dosage cohort experienced an ACTG Grade
4 elevation in ALT levels, one of whom experienced an elevation
of total bilirubin while also receiving concomitant allopurinol.
After their review of un-blinded data from these patients, the
study's independent Data Monitoring Committee (DMC) recommended
that the 900mg q12h cohort be discontinued and that all other
cohorts of the study continue. The companies accepted the DMC's
recommendations. Enrollment of all remaining cohorts was completed
in November of 2009.
The
company reported top-line results of a Phase 1 study of ritonavir-boosted
RG7227 in healthy volunteers. Ritonavir is an antiviral compound
commonly used at low, sub-therapeutic doses to enhance or "boost"
the pharmacokinetic (PK) profiles of protease inhibitors. The
results of this study demonstrated that the co-administration
of low-dose ritonavir increased RG7227 concentration 12 hours
post dose by 18 times, with the effect on Cmin being roughly 6
times and 3 times greater than the effect on Cmax and AUC, respectively.
These results guided the selection of the substantially lower
doses of RG7227 investigated in the Phase 1b MAD study in HCV
patients.
The
company reported preliminary, top-line results of a Phase 1b multiple-ascending-dose
(MAD) study that was initiated in September 2009 to evaluate low
doses of once-daily and twice-daily RG7227 co-administered with
low-dose ritonavir in combination with SOC for 15 days in treatment-naive
HCV-infected patients. This study is examining the following three
dosage regimens of RG7227, each with SOC and 100 mg twice-daily
ritonavir: 100mg twice-daily RG7227; 200mg once-daily RG7227;
200mg twice-daily RG7227. Preliminary viral kinetic data from
the first two cohorts of this study indicate that in the presence
of SOC, the majority of patients achieved an undetectable level
of HCV RNA after 15 days of treatment. The pharmacokinetic profile
of ritonavir-boosted RG7227 was more favorable and less variable
than that observed in previously reported studies conducted with
much higher doses of un-boosted RG7227. No drug related serious
adverse events have been reported to date. The companies hope
to present the results from this study at a medical conference
in the first half of 2010.
Based
upon these results, the company's plan is that the development
of RG7227 will be in combination with low-dose ritonavir. Accordingly,
the previously planned 24-week un-boosted part of the on-going
Phase 2b triple combination study will now be replaced with a
Phase 2b ritonavir-boosted study that is expected to begin in
Q3 of 2010. As a result of not conducting Part B of the Phase
2b study, the company will un-blind the Part A 12-week cohorts
earlier than originally planned and expects to provide both 4-week
RVR data and 12-week EVR data late in the first quarter or early
in the second quarter of 2010. In addition, the companies plan
to amend the on-going Phase 1b MAD 15-day ritonavir boosting study
to evaluate 12 weeks of RG7227 ritonavir-boosted therapy plus
SOC.
The
full press release is available online.
For more information about InterMune, visit http://www.intermune.com.
Idenix Pharmaceuticals Highlights Progress in Three HCV Programs
IDX184: Nucleotide HCV Polymerase Inhibitor
The phase II clinical trial, initiated in the fourth quarter of
2009, is a randomized, double-blind, placebo-controlled, sequential
dose-escalation study evaluating the safety, tolerability, pharmacokinetics
and antiviral activity of IDX184 in combination with pegylated
interferon and ribavirin in treatment-naive HCV genotype 1-infected
patients. Patients will receive a daily dose of IDX184 or placebo
plus pegylated interferon and ribavirin for 14 days and then continue
on pegylated interferon and ribavirin for an additional 14 days.
Antiviral activity will be assessed at the 14-day and 28-day timepoints.
Four dosing regimens of IDX184 ranging from 50 to 200 mg per day
will be evaluated. In the 100 mg and 200 mg cohorts, QD and BID
regimens will be compared. Each cohort includes 20 patients randomized
4:1, IDX184:placebo. This study is being conducted at multiple
centers in the United States and Argentina.
|
Interim
analysis of the first 10 patients randomized into the first
cohort (50 mg QD):
|
|
Cohort
|
Median
Change
in HCV RNA
(log10) at Day 14
|
Patients
with
Undetectable Viral
Load at Day 14
(<15 IU/mL)
|
50
mg/day IDX184 +
PegIFN/Ribavirin (n=8) |
-3.66
|
2
|
| Placebo
+ PegIFN/Ribavirin (n=2) |
-1.70
|
0
|
Median
ALT and AST levels, markers of liver injury, improved during treatment.
There were no serious adverse events on treatment, no treatment
discontinuations and laboratory profiles were comparable to standard
PegIFN/Ribavirin treatment.
"We are very encouraged by these interim data for IDX184
combined with pegylated interferon and ribavirin and look forward
to seeing additional data as the study progresses," said
Douglas Mayers, M.D., Idenix's executive vice president and chief
medical officer.
IDX375: Non-Nucleoside HCV Polymerase Inhibitor
A Phase I single ascending dose study evaluating the safety, tolerability
and pharmacokinetics of IDX375 in healthy volunteers is ongoing.
The first five cohorts (25 mg QD, 50 mg QD, 100 mg QD, 200 mg
QD and 200 mg BID; 6 active:2 placebo) in this double-blind, placebo-controlled
study have been completed. Data suggest favorable plasma exposure
of IDX375 with a long elimination half-life of 32-40 hours demonstrating
the potential for once- or twice-daily dosing in patients. IDX375
was generally safe and well tolerated. There were no significant
lab abnormalities. The most common adverse event was mild diarrhea
(3/30 subjects). Additional cohorts with higher single and multiple
doses are planned.
IDX320: HCV Protease Inhibitor
A Clinical Trial Application for a new protease inhibitor clinical
candidate, IDX320, was filed in December 2009. IDX320 is a non-covalent
macrocyclic inhibitor with nanomolar potency, broad genotypic
coverage and a favorable preclinical pharmacokinetic profile supporting
the potential for once-daily dosing in man.
"We are pleased with these early data from our clinical programs
and look forward to their continued advancement throughout the
year," said Jean-Pierre Sommadossi, Ph.D., chairman and chief
executive officer of Idenix. "In addition, we are excited
about our new protease inhibitor clinical candidate, IDX320, and
expect to begin a phase I clinical trial soon. With three promising
clinical programs that span major HCV drug classes, Idenix is
well positioned to play an important role in the transformation
of the HCV treatment paradigm."
The
full press release is available online.
For
more information about Idenix, see www.idenix.com.
1/22/10
Sources
Vertex. Vertex Reviews 2010 Business Priorities to Support Goal
of Becoming Fully-Capable Biopharmaceutical Company. Press release.
January 10, 2010.
InterMune. InterMune Provides Program Update and 2010 Milestones
for RG7227 (ITMN-191). Press release. January 11, 2010.
Idenix. Idenix Pharmaceuticals Highlights Progress in Three HCV
Programs. Press release. January 11, 2010.
