As Need Grows for New HIV Treatments, Investigational Drug T-20 Shows Continued Potency and Tolerability

BASEL, Switzerland and DURHAM, NC 1st Feb 00 - A member of a new class of anti-HIV drugs, called fusion inhibitors, with the potential to change the treatment landscape were featured in discussion at a symposium this week entitled, "New Targets: Entry Inhibitors" at the 7th Conference on Retroviruses and Opportunistic Infections in San Francisco.

The investigational drug T-20, being developed through the collaboration of F. Hoffmann - La Roche Ltd and Trimeris, Inc., is the first member of a class of compounds known as fusion inhibitors. Fusion inhibitors work specifically on the virus to prevent it from fusing with the cell. A second-generation fusion inhibitor, T-1249, is currently being evaluated in Phase I clinical studies. T-20 and T-1249 are the only fusion inhibitors currently in clinical development. Because they target a unique part of the viral lifecycle, T-20 and T-1249 are not expected to be cross-resistant to existing anti-HIV drugs.

"Developing regimens that include anti-HIV drugs designed to attack the virus in new ways is one of the most pressing unmet medical needs in HIV therapeutics today," said Dr. David Ho, Director of the Aaron Diamond Center for AIDS Research. "As many as 40% of HIV/AIDS patients have failed multiple treatment regimens or have developed resistance to existing options, and while AIDS-related deaths have declined, the number of people living with HIV continues to grow. Fusion inhibitors may very well be the first new class of anti-HIV drugs since the introduction of protease inhibitors in 1995."

Thirty-two week results from an ongoing Phase II clinical study of T-20 (T20-205) are demonstrating consistent trends in tolerability and a decline in plasma viral load as was observed with initial 16-week data, announced in September 1999 at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. New data from this study suggest a substantial CD4 cell increase in addition to the observed viral load decline. The open label single-arm study is evaluating T-20 in combination with other antiretrovirals in 71 HIV-positive adults who had received T-20 during earlier trials.

"Based on the encouraging results we’re seeing, we have recently extended this trial to allow these advanced patients to continue on T-20 beyond 48 weeks," said Dr. Sam Hopkins, senior vice president of medical affairs at Trimeris. "The long-term tolerability of T-20 in combination with other anti-HIV drugs in this trial, as well as the sustained response, exceeded the expectations we had when we initially designed this open label roll-over study for these patients with advanced HIV infection."

Roche and Trimeris also report that accrual is continuing in two additional ongoing studies involving their fusion inhibitors: a Phase II study (T-20-206) evaluating the safety and dosing of T-20 in NNRTI-naïve, protease inhibitor-experienced patients, and a Phase I study of T-1249 (T-1249-101), assessing the safety, pharmacokinetics and tolerability of this compound.

T-20 is administered as a twice-daily subcutaneous injection; in all studies conducted to date, a low dropout rate was observed, indicating that this mode of drug delivery is a viable option for the drug’s administration. 

This new class of anti-HIV drugs known as fusion inhibitors belongs to a broader category of investigational drugs known as "entry inhibitors." Entry inhibitors work in various ways to block HIV before it takes over the cell, either on the virus itself or on the cell. The entry inhibitor category includes the fusion inhibitor class, as well as two other classes: attachment inhibitors and co-receptor inhibitors. The fusion inhibitors, led by T-20, are the furthest along in development of any compound in the entry inhibitor category.

In addition to clinical advances, Trimeris and Roche are making progress on the manufacturing of T-20 and T-1249. The companies have announced the successful transfer of methods to the Roche Boulder, Colorado manufacturing facility for the production of large-scale clinical batches. In July 1999, Trimeris and Roche signed an agreement for the full-scale clinical testing and development of T-20 and T-1249.