In its bid to become the first approved member of a new class of HIV medications, the attachment inhibitor BMS-663068, also known as "068" or fostemsavir, showed similar efficacy to ritonavir (Norvir)-boosted atazanavir (Reyataz) in Phase 2b study results presented at IDWeek 2014.
BMS-663068 is one of a few antiretrovirals in development that are specifically being explored as potential options for HIV treatment-experienced people. The appeal of 068 in this role lies partly in its resistance profile, which to date has shown no cross-resistance with other drug classes in lab tests. The drug also appears to be similarly active regardless of viral tropism, which is noteworthy given the tendency for many people with considerable HIV drug resistance to transition from CCR5-tropic to CXCR4-tropic virus.
The drug's mechanism of action is nicely outlined in an article by Liz Highleyman posted on HIVandHepatitis.com earlier this year. That piece also recaps an early set of 24-week study results presented at CROI 2014 back in March.
The study presented here at IDWeek included additional information regarding the drug's efficacy stratified by race, age, sex, baseline viral load, and baseline CD4 count. On all fronts, according to study presenter Cynthia Brinson of Central Texas Clinical Research in Austin, Texas, 068 performed comparably across all experimental drug doses and in comparison to boosted atazanavir.
The Phase 2B study has five arms, each of which has between 49 and 51 volunteers. Study volunteers were required to have received antiretroviral therapy for a minimum of one week (a pretty loose definition of "treatment experienced"), and have a baseline HIV viral load of 1,000 or greater and a baseline CD4 count of at least 50. In actuality, a substantial subset of volunteers -- ranging from 35% to 51%, depending on the study arm -- had a baseline viral load over 100,000, and between 33% and 41% of volunteers had a baseline CD4 count below 200.
Volunteers were also required to have susceptibility to atazanavir, raltegravir (Isentress) and tenofovir (Viread) -- which was good, because the five study arms were divided by drugs received:
- 068 at 400 mg twice daily + tenofovir + raltegravir
- 068 at 800 mg twice daily + tenofovir + raltegravir
- 068 at 600 mg once daily + tenofovir + raltegravir
- 068 at 1200 mg once daily + tenofovir + raltegravir
- ritonavir-boosted atazanavir at 300/100 mg once daily + tenofovir + raltegravir
This is an impressively diverse study population: 40% of the volunteers were female and 38% were of white race, according to Brinson.
The overall findings, as noted in the CROI presentation earlier this year, were that all doses of 068 performed similarly to boosted atazanavir through 24 weeks in terms of virologic suppression to below 50 copies/mL. Specific rates varied by study arm, but ranged from roughly 70% to approximately 80% in a modified intent-to-treat analysis, and in the low-to-middle 80% range in an observed population analysis.
These percentages bore out in an observed analysis broken down by gender (male versus female), age (below 40 years versus 40 years and up) and race (white versus black versus "other"). Across all study arms and when comparing 086 arms to boosted atazanavir arms, there were no notable differences in virologic suppression rates.
Virologically, 068 and boosted atazanavir both performed similarly regardless of baseline viral load or CD4 count, at least in the limited stratifications included in this analysis. However, it's worth noting that all five study arms exhibited a trend toward worse performance among volunteers with a baseline viral load of 100,000 or higher -- viral suppression at week 24 ranged from roughly 75% to roughly 85% for people with a baseline viral load of 100,000 or higher, compared to a range of around 80% to higher than 90% for people with a baseline viral load below 100,000. Similar splits occurred according to CD4 count: Viral suppression rates ranged from approximately 60% to around 80% among those with a baseline CD4 count below 200, and generally climbed into the mid-to-high 80% range among those with a baseline CD4 count of 200 or higher.
Speaking of CD4 count: Immunology speaking, for the most part, CD4 count increases were very similar across study arms regardless of gender, race or age. One exception was with mean CD4 increase stratified by race, where black volunteers receiving boosted atazanavir appeared to experience greater CD4 gains than black volunteers in the 068 study arms through 24 weeks. (Sample sizes were relatively small, however.) Volunteers with a baseline viral load of 100,000 or higher also exhibited a "suggestion of a trend," in Brinson's words, toward greater CD4 gains compared to volunteers with a baseline viral load below 100,000.
During a question-and-answer period following her presentation, Brinson noted that although there is a possibility that people can develop resistance to 068, none of the volunteers had developed resistance through the 24-week mark of the study. (The trial will ultimately last for 96 weeks.)
Later in this conference, we'll see 24-week safety data associated with this study; Jacob Lalezari will present those findings on Oct. 11.
Myles Helfand is the editorial director of TheBody.com and TheBodyPRO.com.
Follow Myles on Twitter: @MylesatTheBody.