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EACS 2017: Fostemsavir Controls Viral Load in Half of People with Highly Drug-Resistant HIV

Fostemsavir, a new experimental attachment inhibitor, suppressed viral load in over half of participants with extensive drug resistance when added to a background regimen selected by resistance testing, Max Lataillade of ViiV Healthcare reported at the recent 16th European AIDS Conference in Milan.

[Produced in collaboration with aidsmap.com]

The findings come from the Phase 3 BRIGHTE study carried out in the United States, France, and Brazil.

Fostemsavir (formerly BMS-663068) is a new experimental HIV attachment inhibitor which binds to the HIV gp120 protein, preventing HIV attachment to CD4 cells. Other inhibitors of HIV entry, enfuvirtide and maraviroc, have limited roles in HIV treatment. Enfuvirtide is an HIV fusion inhibitor, an injectable agent that is prescribed only for people with no other treatment options. Maraviroc is a CCR5 antagonist; it prevents HIV from using the CCR5 receptor on the surface of CD4 cells to gain entry to the cell. It is used in treatment-experienced people.

Fostemsavir is being developed by ViiV Healthcare for use in treatment-experienced people with resistance to several classes of antiretroviral drugs. The drug was acquired from Bristol-Myers Squibb along with several other experimental antiretrovirals in 2016.

Clinical trials of fostemsavir have tested the drug in people with HIV who have 2 or fewer active classes of antiretroviral drug available to them.

A substantial minority of people living with HIV who began treatment in the mid-1990s have been exposed to suboptimal regimens and have developed resistance to nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and most protease inhibitors. For these individuals, a regimen consisting of an integrase inhibitor and other drugs with partial activity against drug-resistant virus might be assembled, but how long such regimens can be expected to prevent viral rebound is unclear.

A Phase 3 study of fostemsavir, designed to lead to the licensing of the drug for use in treatment-experienced people, randomized participants to receive fostemsavir 600 mg twice daily or placebo for 7 days in addition to their failing regimen, after which all participants received fostemsavir for 24 weeks together with a background regimen that had been optimized by resistance testing.

Treatment-experienced people were eligible for the randomized study arm if they were unable to assemble a regimen that was likely to be fully suppressive from currently available agents and only had sensitivity to drugs in 1 or 2 classes of antiretrovirals.

The study also included an open-label arm for participants without any fully active drug options in the existing classes of antiretroviral agents, who started treatment with fostemsavir and a background regimen optimized by resistance testing.

A total of 272 people were randomized in a 3:1 ratio in the placebo-controlled arm of the study, while 99 people were recruited into the open-label arm.

The study population was at high risk of further HIV disease progression and in need of new treatment options. The median CD4 cell count was 100 cells/mm³ in the placebo-controlled group and 41 cells/mm³ in the open-label group. 72% of all study participants had a baseline CD4 cell count below 200 cells/mm³ and 41% below 50 cells/mm³, indicating a very high risk of AIDS-related illness.

In addition, 80% of study participants had prior exposure to an integrase inhibitor and over 90% were exposed to protease inhibitors. Less than half in the randomized group had more than one fully active agent in their optimized background regimen (42%). Of the 272 participants randomized, 45 (17%) withdrew by week 24. In the open-label group, 26 of 99 participants (26%) withdrew by week 24.

The primary study endpoint was the mean change in viral load (HIV RNA) from day 1 to day 8 in the randomized cohort. Viral load fell by a mean of 0.79 log in the fostemsavir group and 0.17 log in the placebo group, a difference of 0.625 log (p<0.001).

Just under half of participants in the fostemsavir group experienced a viral load reduction of >1 log (46%) and 65% experienced a reduction of >0.5 log. Among those with a baseline viral load >1000 copies/mL (90% of all participants), the median decrease in viral load was 1 log.

At week 24, 54% of participants in the randomized cohort had a viral load below 40 copies/mL, 32% had a viral load above 40 copies/mL and were still taking study medication, 3% had discontinued due to lack of efficacy, adverse events or death, and 6% had changed their optimized background regimen and were classified as having virological failure.

Serious adverse events occurred in 30% of participants (including the non-randomized group) and led to discontinuation of study drug in 6% of all participants. These included AIDS-related infections and other events reflecting the advanced HIV disease of study participants. The most common grade 2-4 drug-related adverse events were nausea, diarrhea, headache, vomiting, fatigue, and weakness (asthenia).

Fostemsavir has been designated a Breakthrough Therapy by the U.S. Food and Drug Administration (FDA) as it addresses an unmet need and it will receive rapid review when submitted for licensing. The FDA is expected to review a licensing application in 2019 or 2020.

11/30/17

Source

M Kozal et al (M Lataillade presenting). Phase 3 study of fostemsavir in heavily treatment-experienced HIV-1 infected participants: day 8 and week 24 primary efficacy and safety results (BRIGHTE study, formerly 205888/AI438-047). 16th European AIDS Conference. Milan, October 25-27, 2017. Abstract PS8/5.