U.S. FDA Approves FUZEON(TM); First Drug to Block Entry of HIV into Immune Cells
Baby Peanut
NUTLEY, N.J., and DURHAM, N.C., March 13 /PRNewswire-FirstCall/ --
Roche and Trimeris, Inc. (Nasdaq: TRMS - News) announced today that
FUZEON(TM) (enfuvirtide), a novel treatment for HIV-1, has been
granted accelerated approval by the U.S. Food and Drug Administration
(FDA) following a six-month priority review. FUZEON in combination
with other antiretroviral agents is indicated for the treatment of
HIV-1 infection in treatment-experienced patients with evidence of
HIV-1 replication despite ongoing antiretroviral therapy.
FUZEON is the first fusion inhibitor, representing the first new class
of anti-HIV treatments in seven years. Unlike all currently approved
anti-HIV drugs, FUZEON blocks the virus from entering the human immune
cell, preventing HIV replication that can devastate the immune systems
of HIV infected individuals.
"This new fusion inhibitor is a significant breakthrough and its
approval is a milestone event in the HIV epidemic," said Dr. Michael
Saag, Director, AIDS Outpatient Clinic, University of Alabama at
Birmingham. "Patients are becoming resistant to our best therapies and
they need new options. This drug attacks the virus in a new way, so it
can work for patients whose virus is resistant to other therapies."
"Almost one million people in the United States are living with
HIV/AIDS, and over 28,000 of those people are living here in New
Jersey. Today, thanks to Roche, whose U.S. headquarters is located
right here in Nutley, New Jersey, there is new hope for these
patients. Today, the FDA approved FUZEON, the first in a new-class of
HIV drugs called fusion inhibitors. I am extremely proud that Roche,
and its 3,000 employees who live and work in New Jersey, together with
their partner Trimeris Inc., are responsible for this incredible
breakthrough in the treatment for HIV/AIDS," said Rep. Bill Pascrell
(D-New Jersey). "New Jersey's AIDS Drug Assistance Program helps
provide these life-sustaining HIV treatments to approximately 3,400
uninsured and underinsured individuals. In Congress, I've worked and
will continue to work towards greater funding for this important
program."
Pivotal Data
The regulatory submission for FUZEON was based on data from two
24-week Phase III pivotal studies of approximately 1,000 patients,
TORO (T-20/FUZEON vs. Optimized Regimen Only) 1, conducted in North
America and Brazil, and TORO 2, conducted in Europe and Australia.
These studies showed that treatment-experienced patients receiving
FUZEON as a part of an optimized background regimen (individualized
combination of anti-HIV drugs) experienced greater immunologic
improvements and were twice as likely to achieve undetectable plasma
levels of HIV (HIV-1 RNA of <400 copies/mL) compared to patients
receiving an individualized regimen alone. In addition, those patients
with two or more active drugs in their background regimen were more
likely to achieve undetectable levels of HIV.
Because of the public health implications, The New England Journal of
Medicine (NEJM) will post the clinical results from the FUZEON TORO 1
study on its web site, www.nejm.org in advance of publishing the data
in an upcoming issue.
"With FUZEON, what we've essentially done is to take a piece of the
virus and turn it against itself. The safety and efficacy of this new
molecule were demonstrated through two rigorously-designed pivotal
studies conducted in a diverse treatment-experienced patient
population," said Dr. Dani Bolognesi, Chief Executive Officer,
Trimeris. "Together with our partner Roche, Trimeris is proud to bring
this innovative new therapy to the growing number of people with HIV
who are in need of new treatment options."
"FUZEON is yet another example of Roche's long-standing commitment to
advancing the treatment of HIV," said George B. Abercrombie, President
and Chief Executive Officer, North American Pharmaceuticals
Operations, Roche. "FUZEON also represents a major advancement in the
large-scale chemical synthesis of peptides. This cutting edge process
has been successfully implemented at the Roche manufacturing facility
in Boulder, Colorado. FUZEON adds an important dimension to our
growing HIV product portfolio and opens the door for a new treatment
paradigm in HIV."
Supply and Distribution of FUZEON
Roche and Trimeris have committed to make FUZEON available for
distribution before the end of March. Because initial demand for
FUZEON may exceed supply following commercial availability, Roche and
Trimeris have developed and are now finalizing a US Progressive
Distribution Plan to provide FUZEON to patients and to ensure
uninterrupted supply to patients once they begin therapy. The details
of this US Progressive Distribution Plan will be announced in the near
future.
Approved Indication
FUZEON in combination with other antiretroviral agents is indicated
for the treatment of HIV-1 infection in treatment-experienced patients
with evidence of HIV-1 replication despite ongoing antiretroviral
therapy. This indication is based on analyses of plasma HIV-1 RNA
levels and CD4 cell counts in controlled studies of FUZEON of 24
weeks' duration. Subjects enrolled were treatment-experienced adults;
many had advanced disease. There are no studies of FUZEON in
antiretroviral naive patients. There are no results from controlled
trials evaluating the effect of FUZEON on clinical progression of
HIV-1.
This indication is reflective of a policy shift within the anti-viral
division at FDA designed to ensure that indications more closely
reflect the patient populations studied.
More About FUZEON
FUZEON 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 Phase III clinical studies, 98
percent of patients had at least one local injection site reaction.
The addition of FUZEON to background antiretroviral therapy generally
did not increase the frequency or the severity of the majority of
adverse events. There was less than five percent difference in the
most common adverse events seen between FUZEON plus an individualized
regimen of antiretroviral drugs and individualized regimen alone. The
events most frequently reported in subjects receiving FUZEON plus an
individualized regimen were diarrhea (26.8%), nausea (20.1%), and
fatigue (16.1%). All these events were seen at a lower incidence than
in subjects that received background regimen alone: diarrhea (33.5%),
nausea (23.7%), and fatigue (17.4%). The most common adverse events
seen more frequently in patients receiving FUZEON plus an
individualized regimen than in patients who received treatment without
FUZEON include headache (11.8%), peripheral neuropathy (8.9%),
dizziness (6.6%), insomnia (11.3%), depression (8.6%), decreased
appetite (6.3%), asthenia (5.7%), myalgia (5.0%), constipation (3.9%)
and pancreatitis (2.4%). The majority of adverse events were of mild
or moderate intensity. Hypersensitivity reactions have been associated
with FUZEON therapy (less than or equal to 1 percent) and have
recurred on rechallenge. In addition, an increased rate of bacterial
pneumonia was observed in patients treated with FUZEON in the Phase
III clinical trials compared to the control arm. It is unclear if the
increased incidence of pneumonia is related to FUZEON use.
Roche in HIV
Roche is at the forefront of efforts to combat HIV infection and AIDS,
committed for 15 years to groundbreaking research and development of
new drugs and diagnostic technology. Roche's objective is to provide
tailored treatment solutions and an improved standard of care
worldwide for people living with HIV.
About Roche
Hoffmann-La Roche (Roche), based in Nutley, N.J., is the U.S.
prescription drug unit of the Roche Group, a leading research-based
health care enterprise that ranks among the world's leaders in
pharmaceuticals, diagnostics and vitamins. Roche discovers, develops,
manufactures and markets numerous important prescription drugs that
enhance people's health, well being and quality of life. Among the
company's areas of therapeutic interest are: dermatology;
genitourinary disease; infectious diseases, including influenza;
inflammation, including arthritis and osteoporosis; metabolic
diseases, including obesity and diabetes; neurology; oncology;
transplantation; vascular diseases; and virology, including HIV/AIDS
and hepatitis C. For more information on the Roche pharmaceuticals
business in the United States, visit the company's Web site at:
http://www.rocheusa.com.
About Trimeris, Inc.
Trimeris, Inc. (Nasdaq: TRMS - News) is a biopharmaceutical company
engaged in the discovery, development and commercialization of novel
therapeutic agents for the treatment of viral disease. The core
technology platform of fusion inhibition is based on blocking viral
entry into host cells. FUZEON(TM), just approved by the FDA, is the
first in a new class of anti-HIV drugs called fusion inhibitors. A
Marketing Authorisation Application (MAA) has also been submitted for
FUZEON in the European Union. Trimeris' second fusion inhibitor
product candidate, T-1249, has received fast track status from the FDA
and is in Phase I/II clinical testing. Trimeris is developing FUZEON
and T-1249 in collaboration with F. Hoffmann-La Roche Ltd. For more
information about Trimeris, please visit the company's website at
www.trimeris.com.
Trimeris Safe Harbor Statement
This document and any attachments may contain forward-looking
information about the Company's financial results and business
prospects that involve substantial risks and uncertainties. These
statements can be identified by the fact that they use words such as
"expect," "project," "intend," "plan," "believe" and other words and
terms of similar meaning. Among the factors that could cause actual
results to differ materially are the following: there is uncertainty
regarding the success of research and development activities,
regulatory authorizations and product commercializations; the results
of our previous clinical trials are not necessarily indicative of
future clinical trials; and, our drug candidates are based upon novel
technology, are difficult and expensive to manufacture and may cause
unexpected side effects. For a detailed description of these factors,
see Trimeris' Form S-3 filed with the Securities and Exchange
Commission on September 27, 2002 and its periodic reports filed with
the SEC.
FACTS ABOUT FUZEON(TM) (enfuvirtide)
Indication
* FUZEON(TM) (enfuvirtide), the first in a new class of anti-HIV
drugs
known as fusion inhibitors, was granted accelerated approval by
the U.S.
Food and Drug administration (FDA) on March 13, 2003. FUZEON in
combination with other antiretroviral agents is indicated for
the
treatment of HIV-1 infection in treatment-experienced patients
with
evidence of HIV-1 replication despite ongoing antiretroviral
therapy.
This indication is based on analyses of plasma HIV-1 RNA levels
and CD4
cell counts in controlled studies of FUZEON of 24 weeks'
duration.
Subjects enrolled were treatment-experienced adults; many had
advanced
disease. There are no studies of FUZEON in antiretroviral naive
patients. There are no results from controlled trials
evaluating the
effect of FUZEON on clinical progression of HIV-1.
Fusion Inhibition
* FUZEON leads the first new class of anti-HIV drugs, fusion
inhibitors,
to be introduced in seven years. Unlike other classes of HIV
drugs that
work after HIV has entered the human immune cell and begun its
replication process, FUZEON blocks entry of HIV into the human
CD4 or
immune cell.
* HIV utilizes a protein, gp41, to fuse with and enter a healthy
immune
cell. FUZEON blocks the gp41 protein and disrupts the
structural
rearrangement necessary for the virus to fuse, or join, with the
healthy
immune cell, consequently inhibiting HIV infection.
* As a result of its unique mechanism of action, FUZEON is
effective in
patients with prior exposure to antiretroviral therapy, who may
have
developed resistance to the other classes of anti-HIV drugs.
Clinical Trial Results
* The regulatory submission for FUZEON was based on data from two
24-week Phase III pivotal studies of approximately 1,000
patients,
TORO (T-20/FUZEON vs. Optimized Regimen Only) 1, conducted in
North
America and Brazil, and TORO 2, conducted in Europe and
Australia.
These studies showed that treatment-experienced patients
receiving
FUZEON as a part of an optimized background regimen
(individualized
combination of anti-HIV drugs) experienced greater immunologic
improvements and were twice as likely to achieve undetectable
plasma
levels of HIV (HIV-1 RNA of <400 copies/mL) compared to patients
receiving an individualized regimen alone.
* Patients with two or more active drugs in their background
regimen were
more likely to achieve undetectable levels of HIV.
* Further analyses of TORO 1 and TORO 2 showed that response of
patients
in the FUZEON arm surpassed that of patients in the
individualized
regimen alone across all subgroups studied. The benefit of
adding
FUZEON to an individualized background regimen was consistent
across
gender, age, race, baseline immune cell (CD4) count and baseline
viral
load.
Manufacturing
* FUZEON is a 36-amino acid peptide chain containing 14 different
amino
acids, is the most complicated molecule ever produced at such a
large
scale. It requires a 106-step manufacturing process, while a
typical
process involves eight to 12 steps. FUZEON is produced at a
Roche
manufacturing facility in Boulder, Colorado.
-- Targeted annual production of FUZEON, at 3,700 kilograms per
year by
year-end 2004, is 60 to 300 times greater than the annual
production
of other synthetic peptides FUZEON is made with 44 different
raw
materials -- a typical process has about 15
-- 45,000 kilograms of very specialized raw materials (not
including
solvents) are required in order to manufacture 1,000
kilograms of
FUZEON
-- Demands for certain critical materials has necessitated
vendors to
scale up production from 100 kilograms per year to multi-ton
quantities -- an increase of at least 2000 percent
Distribution
* Roche and Trimeris have committed to make FUZEON available for
distribution before the end of March. Because initial demand
for FUZEON
may exceed supply following commercial availability, Roche and
Trimeris
have developed and are now finalizing a US Progressive
Distribution Plan
to provide FUZEON to patients and to ensure uninterrupted supply
to
patients once they begin therapy. The details of this US
Progressive
Distribution Plan will be announced in the near future.
The Collaboration to Develop FUZEON
* Research at the Duke University Center for AIDS Research by Drs.
Dani
Bolognesi and Tom Matthews and team yielded the discovery of
FUZEON. In
1993, Bolognesi and Mathews formed the biotechnology company
Trimeris,
Inc. in Durham, North Carolina to continue the research and
development
of fusion inhibitors.
* In 1999, Roche and Trimeris agreed to collaborate on the
research and
development of FUZEON. The collaboration between the two
companies
provided all of the essential elements for rapid development of
the
fusion inhibitor class. Roche and Trimeris are also working
together on
the development of a second-generation fusion inhibitor.
Ongoing Clinical Trials
* The Phase III studies, TORO 1 and TORO 2, are ongoing.
Durability of
response will be assessed with an analysis of 48-week data from
the
trial.
* Two studies, T20-310 and T20-204 (PACTG P1005, a study being
conducted
by the Pediatric AIDS Clinical Trials Group), are evaluating the
use of
FUZEON in a pediatric patient population.
How Supplied
* FUZEON is a powder that is reconstituted with sterile water
prior to
subcutaneous injection. Each single use vial contains 108 mg of
enfuvirtide for the delivery of 90 mg. FUZEON will be supplied
in a 30-
day kit with all the tools required for self-injection.
Dosing and Administration
* In adults, the recommended dose of FUZEON is 90 mgs twice daily,
injected subcutaneously. In pediatric patients six years and
older, a
dose of 2 mg per kg of body weight (maximum 90 mg) administered
twice-daily, provided FUZEON plasma concentrations similar to
those
obtained in adult patients receiving 90 mg, twice-daily.
More About FUZEON
* FUZEON 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 Phase III clinical
studies,
98 percent of patients had at least one local injection site
reaction.
* The addition of FUZEON to background antiretroviral therapy
generally
did not increase the frequency or the severity of the majority
of
adverse events. There was less than five percent difference in
the most
common adverse events seen between FUZEON plus an individualized
regimen
of antiretroviral drugs and individualized regimen alone. The
events
most frequently reported in subjects receiving FUZEON plus an
individualized regimen were diarrhea (26.8%), nausea (20.1%),
and
fatigue (16.1%). All these events were seen at a lower
incidence than
in subjects that received background regimen alone: diarrhea
(33.5%),
nausea (23.7%), and fatigue (17.4%).
* The most common adverse events seen more frequently in patients
receiving FUZEON plus an individualized regimen than in patients
who
received treatment without FUZEON include headache (11.8%),
peripheral
neuropathy (8.9%), dizziness (6.6%), insomnia (11.3%),
depression
(8.6%), decreased appetite (6.3%), asthenia (5.7%), myalgia
(5.0%),
constipation (3.9%) and pancreatitis (2.4%). The majority of
adverse
events were of mild or moderate intensity.
* Hypersensitivity reactions have been associated with FUZEON
therapy
(less than or equal to 1 percent) and have recurred on
rechallenge. In
addition, an increased rate of bacterial pneumonia was observed
in
patients treated with FUZEON in the Phase III clinical trails
compared
to the control arm. It is unclear if the increased incidence of
pneumonia is related to Fuzeon use.