Attachment inhibitor GSK-934/BMS-068: 96-week subgroup analysis in treatment-experienced patients
29 November 2016. Related: Conference reports, Antiretrovirals, HIV 13 Glasgow 2016.
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. [1]
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. [2]
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. [3]
The compound was acquired by ViiV Healthcare in December 2015 and the full new compound name is GSK3684934. [4]
Comment
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.
References:
- 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:
https://vimeo.com/189136479 - 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.
http://www.croiconference.org/sessions/attachment-inhibitor-prodrug-bms-663068-arv-experienced-subjects-week-96-analysis. - NCT02362503. Attachment inhibitor comparison in heavily treatment experienced patients.
https://clinicaltrials.gov/ct2/show/NCT02362503 - BMS Press Release. Bristol-Myers Squibb to sell its HIV R&D portfolio to ViiV Healthcare, (18 December 2015).
http://news.bms.com/press-release/partnering-news/bristol-myers-squibb-sell-its-hiv-rd-portfolio-viiv-healthcare