Attachment inhibitor GSK-934/BMS-068: 96-week subgroup analysis in treatment-experienced patients
Simon Collins, HIV i-Base
Safety results for the attachment inhibitor GSK-934 (previously called BMS-663068/fostemsavir) combining two late breaker abstracts were reported in an oral presentation by Cyril Llamos from ViiV Healthcare. 
This was a subgroup analysis from a phase 2b randomised dose-ranging study in 251 treatment-experienced patients that used atazanavir/r in the control arm. However, rather than using 2 NRTIs as background drugs, all participants used raltegravir (400 mg twice-daily) plus tenofovir-DF (once-daily) as the background drugs. After 48 weeks, all participants in the GSK-934 arms were switched to the selected dose of 1200 mg once-daily.
Approximate baseline characteristics included median age 39 years (range 20 to 68), 60% of the participants were male, and ethnicity included 40% white, 30% black, 30% other. Mean pre-treatment viral load was 4.85 log copies/mL (SD +/- 0.9 log) and 44% had viral loads >100,000 copies/mL). Mean CD4 count was 230 cells/mm3 (SD +/- 135 cells/mm3) and 39% had <200 CD4 cells/mm3).
Pooled data was presented for all BMS-068 for all participants at 96 weeks, however 30% of the GSK-934 participants and 40% of the control patients discontinued before week 96.
The 96-week efficacy and safety analysis from this study was also reported at CROI earlier in the year, with 61% vs 53% having viral load <50 copies/mL at week 96. 
The new analysis reported similar results for the active vs control arms when looking at subgroups for viral load above/below 100,000 copies/mL and for baseline CD4 above/below 200 cells/mm3, gender, age (above/below 50 years) and race/ethnicity. Similar response rates across the active arms were also seen across the range of baseline susceptibility (especially above/below 1.0 nM).
Although side effects were general mild and similar between group (grade 1 to 4: 91% vs 98%, grade3/4: 12% vs 14%), a lower percentage of drug-related side effect occurred for the attachment inhibitor (grade 2 to 4: 8.5% vs 37%) and there were fewer drug-related discontinuations (2.5% vs 10.0%). the single death in the active arms was unrelated (gun shot wound).
GSK-934 is an attachment inhibitor that attaches to gp-120 near the CD4 binding site and prevent conformational changes needed for attachment. It is active against nearly all HIV-1 subtypes, though not sub-type AE or group O and has no in vitro cross resistance to drugs from other classes.
International phase 3 studies are ongoing in treatment-experienced patients with drug resistance that leaves them sensitive to two or fewer drug classes. 
The compound was acquired by ViiV Healthcare in December 2015 and the full new compound name is GSK3684934. 
As with other drugs in new classes, GSK-934 has the potential to become an essential life-saving option for people with multidrug resistance.
Although this study was not powered to see differences in sub-groups, the lack of any immediate signal is encouraging.
- Llamoso C et al HIV-1 attachment inhibitor prodrug BMS-663068 in antiretroviral-experienced subjects: week 96 safety analysis. Glasgow Congress on HIV Therapy, 23-26 October 2016 (Glasgow 2016). Late breaker oral abstract O335B. Webcast:
- DeJesus E et al. Attachment inhibitor prodrug BMS-663068 in ARV-experienced subjects: week 96 analysis. CROI 2016; 22-25 February, Boston. Poster abstract 472.
- NCT02362503. Attachment inhibitor comparison in heavily treatment experienced patients.
- BMS Press Release. Bristol-Myers Squibb to sell its HIV R&D portfolio to ViiV Healthcare, (18 December 2015).