LISBON- 25 October, 1999 – New data presented today reflect the continued positive clinical trend for T-20, the first in an investigational new class of anti-HIV drugs called fusion inhibitors. Researchers presented results that show that antibodies to T-20 do not appear to impact blood levels of T-20 used in combination with currently available antiretroviral agents. These antibodies did not impact the tolerability of the T-20 regimen through 16 weeks of treatment in 55 evaluable patients.

These results, released at the Seventh European Conference on Clinical Aspects and Treatment of HIV-Infection, are based on analysis of 16-week data from a Phase II clinical trial (T20-205). Patients in this trial received T-20 50mg/twice daily by subcutaneous injection.

These results build on data presented at last month’s ICAAC conference showing that 60% of heavily pre-treated people with HIV who received T-20 responded with a clinically significant reduction of HIV viral load. In addition, 36% of these patients, for whom most treatment options have been exhausted, had HIV levels in blood below the level of quantification (<400 copies/mL) following treatment with a combination regimen that included T-20.

"There is currently an unmet need for new treatment options that are effective in the ever-growing number of HIV-infected patients who have cycled through available drugs. The study results are exciting because the response rates compared favorably to what is normally observed in this advanced patient population. We achieved these results by combining a fusion inhibitor with traditional AIDS drugs," commented lead study investigator Jay Lalezari, MD, of Quest Clinical Research in San Francisco, CA.

Unlike other anti-HIV medications that block HIV replication once the virus has penetrated the human cell, T-20 is a peptide that inhibits HIV fusion, the point at which HIV enters the cell. T-20 is administered twice daily by subcutaneous injection, similar to the way diabetics inject insulin.

"Because T-20 attacks the HIV virus before it enters the cell, it works differently than currently approved anti-HIV drugs. It therefore has the potential to combat strains of the virus that have become resistant to these treatments," said Michael Saag, M.D., director of HIV outpatient care at the University of Alabama at Birmingham. "These exciting results confirm observations from prior short-term T-20 studies where a greater than 98% reduction in viral load was seen when T-20 was given alone. This current trial goes one step further in validating the T-20 proof of concept."

Background on the T20 - 205 Trial

In this Phase II clinical trial, T-20 was given in combination with oral antiretrovirals to 55 HIV-positive adults who had previously received T-20 in earlier trials. At entry, patients had previously been treated with an average of 11 antiretroviral agents, and 93% had a clinical history of exposure to all three currently available classes of anti-HIV drugs. Ninety-three percent of patients demonstrated genotypic evidence of resistance to protease inhibitors (average of five mutations per patient) and 87% demonstrated mutations associated with resistance to reverse transcriptase inhibitors (median of four mutations per patient).

In this protocol, patients received T-20 (50 mg/twice daily via subcutaneous injection) in combination with a median of four oral antiretrovirals. Combinations were individualized to each patient and were chosen based on genotypic analysis evaluating patients’ resistance to anti-HIV medications. Median baseline viral load was 4.9 log₁₀ copies/mL and median CD4+ cell count was 70 cells/mm³.

At 16 weeks, 33 of 55 (60%) of heavily pretreated patients who were given T-20 in combination with oral antiretrovirals responded with a reduction in viral load of 1.0 log₁₀ from baseline or below the level of quantification of 400 copies/mL, (using the Roche AMPLICOR^® HIV-1 MONITOR assay). Furthermore, 20 of 55 (36%) had viral load of below the level of quantification.

The average decrease in viral load for all patients was greater than 90% over the 16-week period.

In all clinical studies to date, most adverse events reported on T-20 were mild or moderate in severity. The most frequent adverse events included fever, headache and lymph node abnormalities, in addition to local irritation resulting from the subcutaneous injection.