Thursday May 16, 1:30 am Eastern Time
Press Release
SOURCE: Roche; Trimeris, Inc.
Roche and Trimeris Announce 24-Week Results From Second Pivotal Study of HIV Fusion Inhibitor T-20
- Second of Two Phase III Studies Meets Primary Endpoint; Companies Will Proceed with Filing US and EU Registration Packages In the Second Half of 2002 -
NUTLEY, N.J., and DURHAM, N.C., May 16 /PRNewswire-FirstCall/ -- Roche and Trimeris, Inc. (Nasdaq: TRMS - News) today announced positive 24-week results from the second pivotal Phase III study of T-20 (TORO 2), just four weeks after reporting similarly positive 24-week results from the first Phase III study of T-20. Together, the results from TORO 2, as well as the results from the first study, TORO 1, will form the basis of the submission to regulatory authorities.
T-20 is the furthest in clinical development in an investigational class of antiretrovirals called fusion inhibitors. Unlike currently approved classes of antiretrovirals that work inside the cell and target viral enzymes involved in the replication of the virus, clinical trials have shown that T-20 inhibits fusion of HIV with host cells before the virus enters the cell and begins its replication process.
The results from the TORO 2 study show that T-20 administered in combination with an optimized antiretroviral treatment regimen provides a significant additional decrease in the amount of virus in the blood as compared to an optimized antiretroviral treatment regimen alone. TORO 2 was conducted in 504 HIV infected patients in Europe and Australia who were treatment-experienced and/or had documented resistance to each of the three classes of currently available anti-HIV drugs.
At baseline, patients had a median HIV RNA level of over 5 log(10) copies/mL and extensive prior exposure to multiple anti-HIV drugs. At 24 weeks, patients who received T-20 as part of their combination regimen achieved a mean reduction in HIV levels of 1.43 log(10) copies/mL compared to a mean of 0.65 log(10) copies/mL for those who were randomized to the control arm, calculated in accordance with the study protocol. The primary efficacy endpoint for the study, the difference in the magnitude of decrease in HIV between the two arms at 24 weeks, was 0.78 log(10) copies/mL and was statistically significant (p<0.0001). Roche and Trimeris expect to present these data in detail at scientific conferences in the next several months.
"This is the second large pivotal study to demonstrate that T-20 significantly enhances the activity of combination therapy in treatment-experienced HIV patients over 24 weeks. The excellent results from TORO 2 confirm and build upon those from TORO 1, the first pivotal study," said Georges Gemayel, Vice President, Specialty Care, Roche. "Taken together, these data represent a significant milestone in our commitment to deliver new options for people living with HIV."
"The positive results from TORO 2 are both clinically and statistically significant. It is remarkable that both TORO studies consistently demonstrate the substantial treatment effect of T-20 across a diverse, treatment-experienced patient population from a number of countries. The Roche and Trimeris collaboration plan to proceed with filing registration packages for T-20 in the US and EU early in the second half of the year," said Dani Bolognesi, Chief Executive Officer, Trimeris. "This important milestone brings T-20, the first member of a new class of antiretrovirals, yet another step closer to patients in need."
Safety Results
Through 24 weeks, as in TORO 1, overall clinical adverse events aside from injection site reactions were similar between T-20 and control groups. Other adverse events (>10%) occurring more frequently in the T-20 group were headache, fever, and asthenia. It was not possible to establish a causal relationship between these other adverse events and T-20. Grade 3 laboratory abnormalities were more frequent in the T-20 group, and Grade 4 laboratory abnormalities were more frequent in the control group. In TORO 2, discontinuation at 24 weeks was 17 percent in the T-20 group and 5 percent in the control group. Patients experiencing virologic failure in the control group could switch to a T-20 regimen and not discontinue the study. While most patients on the T-20 arm experienced injection site reactions, only 3 percent of patients discontinued the study as a consequence.
Early Access to T-20
In November 2001, Roche and Trimeris announced the initiation of the T-20 open-label safety study (T20-305) to provide T-20 to 450 patients around the world. The study is ongoing and is being conducted in Australia, Brazil, Europe and North America. Roche and Trimeris are committed to starting early access programs in the second half of this year when increased drug supply is expected to be available.
Study Design
TORO 2 (T-20 vs. Optimized Regimen Only), previously known as T20-302, and TORO 1 (previously known as T20-301) are randomized, open-label trials that enrolled approximately 1,000 patients at 112 centers worldwide. TORO 2 is being conducted in Australia, Belgium, France, Germany, Italy, The Netherlands, Spain, Sweden, Switzerland and the United Kingdom, TORO 1 is being conducted in North America and Brazil. Patients in the trials were treatment-experienced and/or had documented resistance to each of the three classes of currently-available antiretrovirals. In addition, each patient was required to have a plasma HIV-RNA level of greater than 5,000 copies/mL. Patients are expected to undergo treatment for 48 weeks, with an optional 48-week treatment extension. At entry, genotypic and phenotypic resistance testing was used to aid in the selection of an antiretroviral regimen, consisting of three to five drugs, including if appropriate, up to two newly approved or investigational drugs. After selection of the regimen, patients were randomized 2:1 to receive either the regimen in combination with T-20 or the regimen alone. Patients randomized to T-20 receive T-20 administered as one 90 mg subcutaneous self-injection twice-daily.
Meeting the Growing Need For a New Class of HIV Drugs
One of the biggest challenges facing people living with HIV is resistance to currently available therapies. Thirty to fifty percent of patients are infected with a strain of the virus that has developed resistance to one or more antiretrovirals, thereby reducing the treatment options available to them. Roche and Trimeris are committed to discovering and developing treatments for patients in need of new options and expect to invest approximately half a billion U.S. dollars to bring fusion inhibitors to people living with HIV/AIDS.
Long-Term Commitment to HIV Research and Development
Roche and Trimeris are working together to mobilize the considerable resources required to support the rapid development of T-20, the first member of a new class of investigational anti-HIV drugs known as fusion inhibitors. T-20, currently in Phase III clinical trials, is the furthest along in clinical development in the entry inhibitor class. T-1249, a second-generation fusion inhibitor being developed by Roche and Trimeris, is in Phase I/II clinical trials. Unlike existing AIDS drugs that work inside the cell and target viral enzymes involved in the replication of the virus, clinical trials have shown that T-20 inhibits fusion of HIV with host cells before the virus enters the cell and begins its replication process. In June 2001, Roche and Trimeris announced a joint research agreement to identify and develop additional HIV fusion inhibitor peptides.
T-20 has fast track designation from the FDA in the U.S. for the treatment of HIV-infected individuals. Fast track is granted to facilitate the development and expedite the review of applications for drugs that are intended to treat serious or life-threatening disease and that demonstrate the potential to address an unmet medical need. |
