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ROCHE ANNOUNCES SUBMISSION OF REQUEST TO FDA FOR APPROVAL OF T-20
Reported by Jules Levin
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T-20 is a key new drug important for individuals who have limited or few
treatment options. T-20 is a fusion inhibitor and from a new class of drugs
so patients should be fully susceptible to T-20; they should not have any
resistance to T-20. It has been shown to be potent in the two studies
described below for patients with resistance to the current classes of drugs
and who have few treatment options remaining. T-20 is administered by
subcutaneous injections twice daily and patients will have to be instructed
on proper administration procedures. Below is the Press release for your
review that Roche & Trimeris released today announcing their submission to
the FDA for approval of T-20. Its expected that T-20 will be available in the
pharmacy by April 2003. The press release reviews some of the key T-20 data
reported at Barcelona, the manufacturing & production concerns and a brief
explanation about how T-20 works to block HIV from reproducing itself. Here
are links to detailed reports on the NATAP website:
T-20: new class of drug about to enter market; fusion inhibitor. Report from
Barcelona Intl AIDS Conf., July 02
www.natap.org/2002/barcelona/day1.htm
T-20 Resistance & T-1249: report from thw Resistance Wksp, July 2002
HIV Activist Jules Levin Comments on T-20 Drug Study
http://www.natap.org/2002/july/071002_1.htm
Roche and Trimeris Submit New Drug Application for FUZEON
First Fusion Inhibitor to be Reviewed by FDA
NUTLEY, NJ and DURHAM, NC (September 17, 2002) - Roche and Trimeris, Inc.
today announced the submission of a New Drug Application (NDA) to the U.S.
Food and Drug Administration (FDA) for approval to market FUZEON
(enfuvirtide), formerly known as T-20. FUZEON is the frontrunner in a new
class of anti-HIV drugs called "fusion inhibitors," developed for the
treatment of HIV-1 infection in combination with other antiretroviral agents.
Roche and Trimeris have requested priority review status from the FDA, which
if granted would enable FUZEON to be reviewed within six months. In parallel
with the filing, Roche and Trimeris confirmed the successful completion of
the next major manufacturing milestone at the Roche Colorado manufacturing
facility - validation of the first three commercial batches of active
ingredient for FUZEON. The companies also plan to file for FUZEON approval
in Europe before the end of September.
Unlike existing anti-HIV drugs that work inside the cell, FUZEON has a unique
mode of action that is designed to block HIV from entering the human immune
cell. Consequently, FUZEON is active against HIV that is resistant to the
currently available classes of anti-HIV drugs.
The regulatory submissions for FUZEON are based on 24-week data from two
large, international Phase III trials, which indicate that patients on FUZEON
plus an individualized background regimen of other antiretroviral drugs were
twice as likely to achieve undetectable levels of HIV in the blood as
compared to patients who received an individualized background regimen alone.
FUZEON also provided a significant increase in immune cells at 24 weeks.
"Managing the treatment experienced patient has become increasingly complex
and requires careful consideration of adherence, tolerability and resistance
issues. The incidence of drug resistant HIV among already treated patients
is growing dramatically. In fact, up to 78 percent of patients receiving
treatment in North America and Europe are infected with a strain of the virus
that has developed resistance to one or more anti-HIV drugs," said Dr. Daniel
Kuritzkes, Director of AIDS Research, Brigham and Women's Hospital, and
Associate Professor of Medicine, Harvard Medical School. "It is clear that
the need for new drugs such as FUZEON, which work in completely new ways to
block HIV, will become ever more urgent."
"These filings are important steps for Roche," said Georges Gemayel, Vice
President, Roche. "Drug resistance among patients with HIV has become one of
the greatest medical challenges we are facing in this epidemic today. This
is why new therapies are needed to help manage the changing face of this
disease. FUZEON was one of the most difficult scientific and manufacturing
challenges we have faced, but despite these challenges we have developed
FUZEON at the fastest pace possible in response to this increasing patient
need. We proceeded in parallel across Europe and North America and pending
approval, anticipate launches early next year."
"FUZEON was designed from the outset to block HIV replication in a completely
different manner than current antiretroviral drugs, while not substantially
adding to the toxicity of other agents. FUZEON's unique mode of action is
designed to block HIV before entering the human cell and if approved, it will
represent the first of a new class of anti-HIV drug in seven years," said Dr.
Dani Bolognesi, CEO, Trimeris. "These milestones are the latest result of
the ongoing joint development program between Roche and Trimeris."
Manufacturing Progress
FUZEON is one of the most challenging molecules ever chemically
manufactured on such a large scale by the pharmaceutical industry. It takes
106 manufacturing steps to produce the active drug substance alone, which is
around ten times more than that of a protease inhibitor. To coincide with
the fast-paced clinical development program, the Roche Colorado manufacturing
plant has been working 24 hours a day, seven days a week in the commercial
scale-up of FUZEON. As a result, Roche and Trimeris have successfully
completed the next major manufacturing milestone - validation of the first
three commercial batches of active ingredient for FUZEON. In addition,
continued investments are being made in the ongoing development of the
manufacturing facility.
Phase III 24-Week Results
The NDA filing for FUZEON is based on 24 week results from two international
Phase III clinical trials, TORO 1 and TORO 2. TORO is an acronym for "T-20
vs Optimized Regimen Only."
In TORO 1, the first Phase III trial, conducted in North America and Brazil,
37 percent of patients who were treated with FUZEON in combination with an
individualized background regimen had undetectable blood levels (less than
400 copies/mL) of HIV at 24 weeks, compared to 16 percent who received an
individualized background regimen alone (p<0.0001). Combination therapy with
FUZEON further reduced HIV viral load to less than 50 copies/mL in 20 percent
of patients as compared to 7 percent who took combination therapy alone
(P=0.0002). Patients in the FUZEON arm experienced a mean CD4+ cell increase
of 76 cells/mm3, as compared to 32 cells/mm3 in the control arm (p<0.0001).
Results from TORO 2, the second Phase III clinical trial, conducted in Europe
and Australia, were consistent with findings from TORO 1. In TORO 2, 28
percent of patients who were treated with FUZEON in combination with an
individualized background regimen had undetectable blood levels (less than
400 copies/mL) of HIV at 24 weeks, compared to 14 percent receiving an
individualized background regimen alone (p<0.0001). Combination therapy with
FUZEON further reduced HIV viral load to less than 50 copies/mL in 12 percent
of patients as compared to 5 percent who took combination therapy alone
(P=0.0099). Patients in the FUZEON arm experienced a mean CD4+ cell increase
of 65 cells/mm3, as compared to 38 cells/mm3 in the control arm (p=0.023).
More About FUZEON
FUZEON, a fusion inhibitor, is administered as a twice-daily subcutaneous
injection. Local injection site reactions were the most frequent adverse
events associated with the use of FUZEON. In clinical studies, 98 percent of
patients had at least one local injection site reaction; however, these
reactions were seldom treatment limiting, with only three percent of patients
discontinuing treatment with FUZEON.
The addition of FUZEON to background antiretroviral therapy generally did not
increase the frequency or the severity of the majority of adverse events.
The absolute difference in the most common adverse events seen between FUZEON
plus an individualized background regimen of antiretroviral drugs and
individualized background regimen alone was less than five percent. The
events most frequently reported in patients receiving FUZEON plus an
individualized background regimen were, headache, peripheral neuropathy,
dizziness (excluding vertigo), insomnia, depression, appetite decrease,
asthenia, myalgia, constipation and pancreatitis. All these events were seen
more frequently in patients receiving FUZEON plus an individualized
background regimen than in patients who received treatment without FUZEON.
The majority of adverse events were of mild or moderate intensity.
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