of HCV Protease Inhibitor Telaprevir Can Shorten Interferon-based
Adding the investigational hepatitis C virus (HCV) protease
(formerly known as VX-950) to standard hepatitis
C therapy using pegylated
interferon plus ribavirin can potentially shorten
treatment from 48 to 24 weeks for people with hard-to-treat
HCV genotype 1, Vertex Pharmaceuticals announced this
week. In the Phase 3 ILLUMINATE trial, previously untreated
patients who showed good virological response at weeks
4 and 12 of therapy did just as well with a 6-month
course of treatment as with the standard 12-month duration,
reaching a sustained virological response rate of 92%.
Vertex plans to file for Food and Drug Administration
(FDA) approval of telaprevir during the fourth quarter
of this year.
Below is an edited excerpt from a Vertex press release describing
the study and its findings.
ILLUMINATE Study Supports 24-Week Telaprevir-Based Therapy Within
a Response-Guided Regimen for People with Hepatitis C Who Had
Not Received Prior Treatment
Viral cure rates of 92% and 88% with 24 and 48-week regimens,
respectively, in people who met certain response criteria
Safety and tolerability results were similar to those
seen in the Phase 3 ADVANCE study
Mass. -- August 10, 2010 -- Vertex Pharmaceuticals Incorporated
(Nasdaq: VRTX) today announced results from the Phase 3 ILLUMINATE
study, which was designed to evaluate whether there was any
benefit to extending therapy from 24 to 48 weeks in people whose
hepatitis C virus (HCV) was undetectable at weeks 4 and 12 of
treatment (extended rapid viral response or eRVR). People in
the trial who met these eRVR criteria and who remained on treatment
were then randomized at week 20 to receive 24 or 48 weeks of
total treatment. People who did not meet these criteria were
assigned to 48 weeks of pegylated interferon and ribavirin therapy.
Sustained viral response (SVR or viral cure) rates of 92% and
88% were observed in the randomized 24 and 48-week telaprevir-based
treatment groups, respectively. 72% of all 540 people treated
with telaprevir in the study achieved a viral cure. The safety
and tolerability profile of the telaprevir-based regimen was
consistent with results reported previously from the pivotal
Phase 3 ADVANCE study.
"The viral cure rates seen in ILLUMINATE showed that there
was no benefit to extending telaprevir-based therapy to 48 weeks
for the majority of people," said Kenneth Sherman, MD,
PhD, Professor of Medicine at the University of Cincinnati College
of Medicine, Director of the Division of Digestive Diseases
for UC Health and Principal Investigator of the trial. "Patients
who had a rapid response to telaprevir-based regimens at weeks
4 and 12 had a high likelihood of achieving a cure with 24 weeks
of total treatment, which may provide important information
to motivate people to continue therapy."
"Data from ILLUMINATE and ADVANCE support our belief that
the use of 24-week telaprevir-based therapy within a response-guided
regimen may provide an important future treatment option for
people with hepatitis C," said Robert Kauffman, MD, PhD,
Senior Vice President and Chief Medical Officer for Vertex.
Telaprevir is an investigational, oral inhibitor of HCV protease,
an enzyme essential for viral replication, and is being developed
by Vertex Pharmaceuticals in collaboration with Tibotec Pharmaceuticals
and Mitsubishi Tanabe Pharma. Results from the ILLUMINATE study
are expected to supplement data obtained from ADVANCE
and REALIZE -- the two pivotal Phase 3 studies of telaprevir
-- as part of a New Drug Application submission to the U.S.
Food and Drug Administration planned for the fourth quarter
Efficacy Results from ILLUMINATE
analysis for people who met certain response criteria*:
24-week telaprevir-based treatment regimen:
- SVR Rate: 92% (149/162)
- Relapse Rate: 5.7% (9/159)
48-week telaprevir-based treatment regimen:
- SVR Rate: 88% (140/160)
- Relapse Rate: 1.9% (3/154)
*Reflects people whose hepatitis C virus was undetectable (<
25 IU/mL and undetectable by Roche COBAS Taqman HCV test) at
weeks 4 and 12 (eRVR) and who remained on treatment through
Overall efficacy analysis for all patients treated with telaprevir
in ILLUMINATE (ITT or intent-to-treat analysis):
- SVR Rate: 72% (388/540)
- Relapse Rate: 7.7% (36/469)
- Rapid Viral Response (RVR) Rate: 72% (389/540)
- Extended RVR (eRVR): 65% (352/540)
& Tolerability Results from ILLUMINATE
The safety and tolerability profile of the telaprevir-based
regimen in the ILLUMINATE study was similar to results reported
from the Phase 3 ADVANCE study. The most common adverse events
reported in the ILLUMINATE study, in order of frequency, were
fatigue, pruritus, nausea, anemia, rash and headache. The majority
of these adverse events were mild or moderate. Adverse events
leading to discontinuation of all study drugs during the 12-week
telaprevir dosing period occurred in 6.9% of people in the study.
Treatment discontinuation of all drugs due to anemia and rash
occurred in 1.1% and 0.6% of people in the study, respectively,
during the telaprevir dosing period. Like in ADVANCE, the use
of erythropoiesis-stimulating agents (ESAs) was not allowed
in this study.
Data from ILLUMINATE have been submitted for presentation at
the 2010 Annual Meeting of the American Association for the
Study of Liver Diseases.
About the ILLUMINATE Trial
ILLUMINATE was a Phase 3, supplemental, open-label, randomized
study in people infected with genotype 1 chronic hepatitis C,
the most common form of the virus in the U.S. and Europe, who
had not been previously treated (treatment-naive). In this study,
people who met protocol-defined response criteria of achieving
eRVR were randomized at week 20 to receive 24 or 48 weeks of
total treatment. The primary endpoint of the study was the proportion
of patients who achieved SVR in the randomized treatment groups,
and evaluated by a non-inferiority analysis. Based on this analysis,
the study achieved its primary endpoint of non-inferiority with
respect to SVR rates in the randomized 24 and 48-week telaprevir-based
arms. The trial enrolled people at 76 clinical trial sites in
the U.S. and Europe. A greater proportion of people in the ILLUMINATE
study (approximately 90%) were enrolled at U.S. sites compared
to the proportion in ADVANCE. As in all studies evaluating telaprevir-based
regimens, patients received no more than 12 weeks of triple
therapy (telaprevir, pegylated-interferon and ribavirin) followed
by pegylated-interferon and ribavirin only, as part of either
24 or 48 weeks of total treatment, as noted in the trial
About the Telaprevir Development Program
To date, more than 2,500 people with hepatitis C have received
telaprevir-based therapy as part of Phase 2 studies and the
Phase 3 ADVANCE, ILLUMINATE and REALIZE trials. Together, these
studies enrolled people with genotype 1 hepatitis C who had
not been treated for their disease previously as well as people
who had been treated before but did not achieve a viral cure.
The telaprevir clinical development program is the largest conducted
to date for any investigational direct-acting antiviral hepatitis
Phase 3 ADVANCE Trial
The pivotal Phase 3 ADVANCE study evaluated telaprevir-based
response-guided regimens in 1,095 treatment-naive patients.
Data from this trial has been accepted for presentation at the
2010 Annual Meeting of the American Association for the Study
of Liver Diseases.
Phase 3 REALIZE Trial
The second pivotal Phase 3 study, REALIZE, which is being conducted
by Vertex's collaborator Tibotec, is evaluating telaprevir-based
regimens in approximately 650 people who did not achieve a viral
cure with a prior pegylated-interferon based treatment. REALIZE
is the only current Phase 3 study of an investigational hepatitis
C therapy to enroll a difficult-to-treat population that includes
patients who had a null response and failed to achieve a viral
cure with a prior course of hepatitis C therapy. Topline data
from REALIZE are expected in September 2010.
Vertex retains commercial rights to telaprevir in North America.
Tibotec has rights to commercialize telaprevir in Europe, South
America, Australia, the Middle East and certain other countries.
Mitsubishi Tanabe Pharma has rights to commercialize telaprevir
in Japan and certain Far East countries.
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 http://www.vrtx.com.
Vertex Pharmaceuticals. Phase 3 ILLUMINATE Study Supports 24-Week
Telaprevir-Based Therapy Within a Response-Guided Regimen for
People with Hepatitis C Who Had Not Received Prior Treatment.
release. August 10, 2010.