- Combination therapy with telaprevir and pegylated interferon suppressed
both wild-type and resistant HCV -
BOSTON, Oct. 27 /PRNewswire-FirstCall/ -- Researchers will present new
data this week suggesting that both wild-type hepatitis C virus and
resistant variants were suppressed in patients when pegylated interferon
(peginterferon alfa-2a; peg-IFN) was added to telaprevir (VX-950), Vertex's
investigational hepatitis C virus (HCV) protease inhibitor, in a Phase 1b
clinical study. In addition, clinical investigators will report that 24 of
26 patients who received telaprevir (VX-950) in two early-stage clinical
trials had undetectable HCV RNA after receiving follow-on combination
therapy with peg-IFN and ribavirin (RBV) through 24 weeks of treatment, a
therapeutic regimen following the conclusion of the clinical trials.
Clinical investigators will also report that some of these patients have
stopped therapy, and that a proportion of them continued to have
undetectable HCV RNA after stopping therapy.
The data will be presented while attending the 57th Annual Meeting of
the American Association for the Study of Liver Diseases (AASLD) and were
released in accordance with media guidelines established by the conference.
Telaprevir (VX-950) is an investigational drug candidate being developed as
part of a global Phase 2b clinical development program by Vertex
Pharmaceuticals Incorporated (Nasdaq: VRTX).
Combination of Telaprevir (VX-950) and Peg-IFN Suppressed Both
Wild-type Virus and Resistance Variants in 14-day Clinical Study
Tara Kieffer, Ph.D., of Vertex will present data in a Presidential
Plenary session on Monday, October 30, analyzing viral sequences isolated
from patients receiving telaprevir (VX-950) as a single agent or in
combination with peg-IFN in a Phase 1b 14-day clinical study. In this
study, viral variants were suppressed when peg-IFN was combined with
telaprevir, or when peg-IFN and RBV were administered subsequent to
telaprevir dosing.
In one arm of the trial, resistant viral variants were isolated from
six of eight patients who had detectable HCV RNA while receiving telaprevir
as a single agent over a period of 14 days. Subsequently, clinical
investigators reported that all patients who received follow-on therapy
with peg-IFN and RBV had undetectable HCV RNA at 24 weeks. In a second arm
of the study, resistant viral variants were isolated from two of eight
patients who received a combination of telaprevir and peg-IFN for 14 days.
Both patients subsequently had undetectable HCV RNA at week 12 of follow-on
therapy.
Current Status of Patients Receiving Follow-On Peg-IFN and RBV
Combination Therapy After a 14-day, Phase 1b Clinical Trial of Telaprevir
(VX-950)
On Tuesday, October 31, Dr. Nicole Forestier of Saarland University
Hospital in Homburg, Germany will review the current status of 20 patients
from a Phase 1b study who received 14 days of telaprevir therapy either
alone or in combination with peg-IFN, or peg-IFN alone, in a poster
presentation titled "Current status of subjects receiving peg-interferon
alfa-2a (peg-IFN) and ribavirin (RBV) after a 14-day study of the hepatitis
C protease inhibitor telaprevir (VX-950), with peg-IFN." Clinical
investigators previously reported that at the end of 14 days of dosing, one
of eight patients receiving telaprevir as a single agent and four of eight
patients receiving telaprevir in combination with peg-IFN had undetectable
HCV RNA (less than 10 IU/mL, Roche Taqman(R)).
All patients who did not discontinue therapy at week 24 are expected to
continue to receive peg-IFN+RBV for a total of 48 weeks of treatment. The
current status of patients, as reported by the poster authors, is described
in the following table:
HCV RNA results for patients receiving follow-on peg-IFN+RBV therapy following
14-day Phase 1b study of telaprevir (VX-950)
Initial Patients Patients Patients Patients who Patients
14-day with with with stopped continuing
regimen undetectable undetectable undetectable therapy at to receive
(number HCV RNA at HCV RNA at HCV RNA at week 24 who peg-
of end of 14 end of 12 end of 24 had IFN+RBV
patients) days of weeks of weeks of undetectable through 48
dosing follow-on follow-on HCV RNA 12 weeks of
treatment treatment weeks post- follow-on
with peg- with peg- treatment therapy
IFN+RBV IFN+RBV
VX-950
alone 1 of 8 5 of 7* 7 of 7 2 of 4** 3
(n=8)
VX-950
peg-IFN 4 of 8 8 of 8 8 of 8 5 of 6** 2
(n=8)
Peg-IFN
alone 0 of 4 1 of 4 3 of 4 - 4
(n=4)
* 1 patient in the VX-950 alone group refused follow-on therapy after the
initial 14-day dosing period.
** At the 24 week timepoint, four of the seven patients originally
randomized to the telaprevir monotherapy arm, and six of the eight
patients originally randomized to the telaprevir+peg-IFN arm, were
determined to be eligible by their physicians to stop treatment at week
24, and following discussions, were willing to stop treatment at that
timepoint in order to assess whether they would maintain undetectable
HCV RNA status. Two of four patients from the telaprevir monotherapy
arm, and one of the six patients from the telaprevir+peg-IFN arm, had
detectable HCV RNA within 12 weeks after stopping treatment.
Current Status of Patients Receiving Follow-On Peg-IFN and RBV
Combination Therapy After a 28-day, Phase 2a Clinical Trial of Telaprevir
(VX-950)
On Monday, October 30, Dr. Maribel Rodriguez-Torres of Fundacion de
Investigacion de Diego, Puerto Rico will review the current status of 12
patients originally enrolled in a 28-day Phase 2a study of telaprevir in a
poster presentation titled "Current status of subjects receiving
peg-interferon alfa-2a (peg-IFN) and ribavirin (RBV) follow-on therapy
after 28-day treatment of the hepatitis C protease inhibitor telaprevir
(VX-950), peg-IFN and RBV." Clinical investigators previously reported that
at the end of 28 days of dosing with telaprevir in combination with peg-IFN
and RBV, 12 of 12 patients had HCV RNA below the limit of detection of a
highly sensitive assay (less than 10 IU/mL Roche Taqman(R)).
The current status of patients, as reported by the poster authors, is
described in the following table:
HCV RNA status of patients receiving follow-on peg-IFN+RBV therapy following
28-day Phase 2a study of telaprevir (VX-950)+peg-IFN+RBV
Time Point On treatment, Stopped HCV RNA Lost to
HCV RNA treatment at detectable follow-up
Undetectable week 18,
HCV RNA
undetectable
6 weeks post-
treatment
At end of 24 weeks
of follow-on peg-
IFN+RBV therapy
(n=12) 8 1 2 1
At the end of 24 weeks of follow-on peg-IFN+RBV therapy, eight patients
who were still receiving peg-IFN+RBV had undetectable HCV RNA. These
patients continue to receive peg-IFN+RBV at week 36 of follow-on therapy.
Additionally, one patient stopped treatment at week 18 and remained HCV RNA
undetectable 6 weeks after stopping therapy (week 24).
Two patients had detectable HCV RNA and stopped treatment at week 24 of
follow-on therapy. In these two patients, viral sequencing analyses at week
24 showed predominantly wild-type virus, with a minority population of
R155K variants also detected. One patient, after having undetectable HCV
RNA at week 12, was lost to follow-up at week 18 of follow-on therapy.
The results reported above represent clinical treatment of
comparatively small numbers of patients who were initially dosed in
clinical trials of telaprevir for 14 or 28 days. These results may not be
predictive of patient outcomes in large clinical trials evaluating
telaprevir.
In clinical studies reported to date, telaprevir has been administered
as a single agent, in combination with peg-IFN only, and in combination
with peg-IFN and RBV for 28 days or less. In subjects who received
telaprevir alone, commonly reported adverse events were headache, diarrhea,
urinary frequency, sleepiness, and skin disorders (dry skin, rash and
itching). In subjects who received telaprevir in combination with peg-IFN
and with or without RBV, the commonly reported adverse events were flu-like
symptoms, fatigue, headache, nausea, anemia, depression, insomnia, and skin
disorders (dry skin, rash and itching). Except for one headache in one
patient receiving telaprevir in combination with peg-IFN and RBV that was
judged to be severe, adverse events across all studies reported to date
were mild to moderate.
Two additional presentations involving telaprevir will be presented at
AASLD:
- Chao Lin, Ph.D., of Vertex will present in vitro analyses on Sunday,
October 29. In Dr. Lin's study, variants with decreased sensitivity to
telaprevir remained sensitive to interferon alpha and ribavirin.
- Raj Kalkeri, Ph.D., of Vertex will present in vitro data on Monday,
October 30. In Dr. Kalkeri's study, HCV protease variants with
decreased sensitivity to telaprevir were less efficient in cleaving
proteins involved in innate immunity.
About Telaprevir (VX-950)
Telaprevir (VX-950) is an investigational oral inhibitor of HCV
protease, an enzyme essential for viral replication, and is one of the most
advanced investigational agents in development that specifically targets
HCV. Vertex is conducting a global Phase 2b clinical development program
for telaprevir consisting of three large clinical trials that are expected
to enroll approximately 1000 patients with HCV at clinical centers in the
United States and Europe. Vertex completed enrollment in the 260-patient,
U.S.-based PROVE 1 trial in September. The PROVE 2 trial is underway in
Europe and is expected to complete enrollment by year-end with
approximately 320 patients. Also in the fourth quarter, Vertex expects to
initiate PROVE 3, a clinical trial of telaprevir that will enroll more than
400 treatment-experienced patients. In clinical trials, telaprevir is being
dosed as 750 mg every eight hours in combination with pegylated interferon
alfa-2a (Pegasys(R)), both with and without ribavirin (Copegus(R)).
Vertex retains commercial rights to telaprevir in North America. Vertex
and Tibotec are collaborating to develop and commercialize telaprevir in
Europe, South America, Australia, the Middle East, and other countries.
Vertex is collaborating with Mitsubishi Pharma to develop and commercialize
telaprevir in Japan and certain Far East countries.
About Hepatitis C
Hepatitis C is a liver disease caused by infection with hepatitis C
virus (HCV), which is found in the blood of people with the disease. HCV, a
serious public health concern affecting 170 million people worldwide, is
spread through direct contact with the blood of an infected person. Though
many people with hepatitis C may not experience symptoms, others may have
symptoms such as jaundice, abdominal pain, fatigue and fever. Hepatitis C
significantly increases a person's risk of developing chronic liver
disease, cirrhosis, liver cancer and early death.
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,
inflammation, autoimmune diseases, cancer, pain and bacterial infection.
Vertex co-discovered the HIV protease inhibitor, Lexiva, with
GlaxoSmithKline.
Safe Harbor Statement
This press release may contain forward-looking statements, including
statements that (i) the PROVE 2 study is expected to complete enrollment by
year-end with approximately 320 patients; and (ii) Vertex expects to
initiate PROVE 3 clinical trials in more than 400 treatment-failure
patients by the end of 2006. While management makes its best efforts to be
accurate in making forward-looking statements, such statements are subject
to risks and uncertainties that could cause the actual results of studies
to vary materially. Those risks and uncertainties include, among other
things, the risk that observed outcomes in clinical investigations of small
numbers of patients will not be reflected in clinical trials involving
larger numbers of patients, that unexpected and adverse outcomes in other
ongoing clinical and nonclinical studies, or discussions with regulators
about study design, will delay initiation of the PROVE 3 study, and other
risks listed under Risk Factors in Vertex's Form 10-K filed with the
Securities and Exchange Commission on March 16, 2006. Vertex disclaims any
obligation to update the information contained in this press release as new
data become available.
Vertex's press releases are available at http://www.vrtx.com.
Vertex Contacts:
Lynne H. Brum, VP, Strategic Communications (617) 444-6614
Michael Partridge, Director, Corporate Communications, (617) 444-6108
Lora Pike, Manager, Investor Relations, (617) 444-6755
Zachry Barber, Senior Media Relations Specialist, (617) 444-6470
SOURCE Vertex Pharmaceuticals Incorporated
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CONTACT:
Lynne H. Brum, VP, Strategic Communications,
+1-617-444-6614, or Michael Partridge, Director, Corporate
Communications, +1-617-444-6108, or Lora Pike, Manager, Investor
Relations, +1-617-444-6755, or Zachry Barber, Senior Media
Relations Specialist, +1-617-444-6470, all of Vertex
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