{"id":35310,"date":"2018-11-13T11:35:01","date_gmt":"2018-11-13T11:35:01","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=35310"},"modified":"2018-11-14T10:21:36","modified_gmt":"2018-11-14T10:21:36","slug":"fostemsavir-48-week-phase-3-results-from-brighte-study","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/35310","title":{"rendered":"Fostemsavir: 48-week phase 3 results from BRIGHTE study"},"content":{"rendered":"

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

Two oral presentations provided 48-week safety, efficacy and subgroup analysis from the investigational gp120 attachment inhibitor fostemsavir.<\/strong><\/p>\n

As the first drug in a new class, this compound is especially important for people with drug resistance to their current last combination.<\/p>\n

Although the primary endpoint was viral suppression to <40 copies\/mL at day 8 after fostemsavir has been added to current failing ART, participants have now reached 48-weeks for secondary efficacy and safety endpoints. Other investigational drugs were allowed during the optimisation phase. The data at Glasgow 2018 update the week-24 results presented last years at the EACS 2017 conference.<\/p>\n

As previously reported, this was an advanced patient group with CD4 count at screening less than 200 cells\/mm3<\/sup>\u00a0in 72% and 50 cells\/mm3<\/sup>\u00a0in 41% of the group. Previous use of integrase inhibitors and protease inhibitors were reported for 80% and 96% respectively.<\/p>\n

Baseline characteristics for the randomised group included median age 44 years (range 18 to 73) and approximately 30% were women. Median (range) CD4 and viral load were approximately 100 cells\/mm3<\/sup>\u00a0(0 to 1160) and 4.7 log copies\/mL (1.6 to 6.9), respectively. Approximately 10% had no fully active drugs in the optimised background regimen (OBR), with 40-50% having only 1 or 2 fully active drugs.<\/p>\n

Baseline characteristics were similar for the open-label group, with the important exception that 80% had no active drugs in the OBR and 20% had only one active drug. In this group, >95% had integrase experience and 70% had used T-20. Of the 19 people with sensitivity to one drug, 13\/19 used the investigational mAb ibalizumab.<\/p>\n

By week 24, viral suppression was reported for 54% of participants, with 71% and 77% using <200 and <400 copies\/mL cut-offs respectively.<\/p>\n

By week 48, follow-up included 79% (215\/272) randomised participants and 68% (69\/99) open label participants. Reasons for withdrawal are shown in Table 1.<\/p>\n

Table 1: Reasons for study withdrawals by week 48\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n
<\/td>\nRandomised<\/td>\nOpen label<\/td>\n<\/tr>\n
<\/td>\nn=57\/272<\/td>\nn=32\/99<\/td>\n<\/tr>\n
AEs<\/td>\n9 (3%)<\/td>\n5 (5%)<\/td>\n<\/tr>\n
Lack of efficacy<\/td>\n12 (4%)<\/td>\n6 (6%)<\/td>\n<\/tr>\n
Non-adherence<\/td>\n11 (4%)<\/td>\n5 (5%)<\/td>\n<\/tr>\n
Withdrawn consent<\/td>\n5 (2%)<\/td>\n1 (1%)<\/td>\n<\/tr>\n
Lost to follow-up<\/td>\n7 (3%)<\/td>\n1 (1%)<\/td>\n<\/tr>\n
No longer met study criteria<\/td>\n3 (1%)<\/td>\n2 (2%)<\/td>\n<\/tr>\n
Death<\/td>\n8 (3%)<\/td>\n12 (12%)<\/td>\n<\/tr>\n
Pregnancy<\/td>\n1 (<1%)<\/td>\n<\/td>\n<\/tr>\n
Other<\/td>\n1 (<1%).<\/td>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

At week 48, by snapshot analysis, 54% participants in the randomised study (146\/272) and 38% (38\/99) in the open label study had viral load <40 copies\/mL. These were similar to rates at week 24.<\/p>\n

Over time, rates were higher by observed analysis: 57% vs 62% <40 copies\/mL, 79% vs 84% <200 copies\/mL and 85% vs 86% using the <400 copies\/mL thresholds – all weeks 24 (n=246) vs 48 (n=233) respectively.<\/p>\n

Mean CD4 responses also steadily increased in both groups over 48 weeks by +139 cells\/mm3\u00a0<\/sup>and +63 cells\/mm3\u00a0<\/sup>in the randomised and open label groups respectively.<\/p>\n

Serious adverse events were common in both arms, reflecting the advanced HIV stage, but were higher in the open label group: 31% vs 44%; grade 3\/4: 26% vs 47%; and deaths 4% vs 14%.<\/p>\n

The sub group analysis by baseline CD4 count showed significant CD4 increases even for those starting with CD4 counts <20 cells\/mm3<\/sup>, although viral response rates were lower for this group (35%).<\/p>\n

Table 2: Fostemsavir subgroup analysis by baseline CD4 count<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n
<\/td>\nHIV viral load <40 c\/mL<\/td>\nChange in CD4 cells\/mm3<\/td>\n<\/tr>\n
BL CD4 \u00a0cells\/mm3<\/td>\nn<\/td>\nn (%)<\/td>\nn<\/td>\nMean change (SD)<\/td>\n<\/tr>\n
20<\/td>\n72<\/td>\n25 (35%)<\/td>\n58<\/td>\n145.2 (109.33)<\/td>\n<\/tr>\n
20\u201350<\/td>\n25<\/td>\n12 (48%)<\/td>\n20<\/td>\n149.0 (93.20)<\/td>\n<\/tr>\n
50\u2013100<\/td>\n39<\/td>\n22 (56%)<\/td>\n30<\/td>\n126.4 (103.62)<\/td>\n<\/tr>\n
100\u2013200<\/td>\n63<\/td>\n37 (59%)<\/td>\n57<\/td>\n123.1 (101.13)<\/td>\n<\/tr>\n
\u2265200<\/td>\n73<\/td>\n50 (68%)<\/td>\n63<\/td>\n150.0 (195.88)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

References<\/p>\n

Unless stated otherwise, references are the the programme and abstract from the Glasgow 2018 conference. These are available online as a supplement to the Journal of the IAS.
\nhttps:\/\/onlinelibrary.wiley.com\/toc\/17582652\/2018\/21\/S8<\/span><\/a><\/p>\n

    \n
  1. Aberg J et al. Week 48 safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced participants (BRIGHTE study)\u2028. Glasgow HIV Congress 2018, 28 \u2013 31 October 2018. Oral abstract O344A.<\/li>\n
  2. Molina J-M et al. Phase III study of fostemsavir in heavily treatment-experienced HIV-1 infected participants: BRIGHTE Week 48 sub- group analysis in randomised cohort participants\u2028.Glasgow HIV Congress 2018, 28 \u2013 31 October 2018. Oral abstract O344B.<\/li>\n<\/ol>\n\n\n","protected":false},"excerpt":{"rendered":"

    Simon Collins, HIV i-Base Two oral presentations provided 48-week safety, efficacy and subgroup analysis from the investigational gp120 attachment inhibitor fostemsavir. As the first drug in a new class, this compound is especially important for people with drug resistance to …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3],"tags":[260],"class_list":["post-35310","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-hiv-glasgow-2018"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/35310","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\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=35310"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/35310\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=35310"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=35310"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=35310"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}