{"id":31019,"date":"2016-11-29T09:30:21","date_gmt":"2016-11-29T09:30:21","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=31019"},"modified":"2017-07-05T09:47:36","modified_gmt":"2017-07-05T09:47:36","slug":"attachment-inhibitor-gsk-934bms-068-96-week-subgroup-analysis-in-treatment-experienced-patients","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/31019","title":{"rendered":"Attachment inhibitor GSK-934\/BMS-068: 96-week subgroup analysis in treatment-experienced patients"},"content":{"rendered":"

\"HIV<\/a><\/p>\n

Simon Collins, HIV i-Base<\/strong><\/p>\n

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.<\/strong> [1]<\/p>\n

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.<\/p>\n

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<\/sup>).<\/p>\n

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.<\/p>\n

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]<\/p>\n

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<\/sup>, 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).<\/p>\n

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).<\/p>\n

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.<\/p>\n

International phase 3 studies are ongoing in treatment-experienced patients with drug resistance that leaves them sensitive to two or fewer drug classes. [3]<\/p>\n

The compound was acquired by ViiV Healthcare in December 2015 and the full new compound name is GSK3684934. [4]<\/p>\n

Comment<\/h3>\n

As with other drugs in new classes, GSK-934 has the potential to become an essential life-saving option for people with multidrug resistance.<\/strong><\/p>\n

Although this study was not powered to see differences in sub-groups, the lack of any immediate signal is encouraging.<\/strong><\/p>\n

References:<\/p>\n

    \n
  1. 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:
    \n    https:\/\/vimeo.com\/189136479<\/a><\/li>\n
  2. DeJesus E et al. Attachment inhibitor prodrug BMS-663068 in ARV-experienced subjects: week 96 analysis. CROI 2016; 22-25 February, Boston.\u00a0\u00a0Poster abstract 472.
    \n    http:\/\/www.croiconference.org\/sessions\/attachment-inhibitor-prodrug-bms-663068-arv-experienced-subjects-week-96-analysis<\/a>.<\/li>\n
  3. NCT02362503. Attachment inhibitor comparison in heavily treatment experienced patients.
    \n    https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02362503<\/a><\/li>\n
  4. BMS Press Release. Bristol-Myers Squibb to sell its HIV R&D portfolio to ViiV Healthcare, (18 December 2015).
    \n    http:\/\/news.bms.com\/press-release\/partnering-news\/bristol-myers-squibb-sell-its-hiv-rd-portfolio-viiv-healthcare<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    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 …<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3],"tags":[235],"class_list":["post-31019","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-hiv-glasgow-2016"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/31019","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=31019"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/31019\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=31019"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=31019"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=31019"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}