{"id":32149,"date":"2017-08-10T12:20:57","date_gmt":"2017-08-10T12:20:57","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=32149"},"modified":"2017-08-15T11:10:37","modified_gmt":"2017-08-15T11:10:37","slug":"phase-3-results-with-bictegravir-a-new-integrase-inhibitor-in-fdc-with-ftctaf","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/32149","title":{"rendered":"Phase 3 results with bictegravir FDC: a new integrase inhibitor combined with FTC\/TAF"},"content":{"rendered":"

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

Results from two phase 3 studies were presented at IAS 2017 on bictegravir, a new integrase inhibitor that is coformulated in a fixed dose combination (FDC) with FTC\/TAF.<\/strong><\/p>\n

Bictegravir has already been submitted to the FDA for regulatory approval in the FDC formulation but it\u00a0will only\u00a0be available as a component of\u00a0the FDC (B\/F\/TAF) rather than as a separate drug.<\/p>\n

Both studies showed bictegravir to be very similar in efficacy to dolutegravir with slight differences in the formulations linked to the background NRTIs in the FDCs.<\/p>\n

Bictegravir FDC compared to dolutegravir\/3TC\/abacavir<\/h2>\n

Joel Gallant from Southwest CARE Center, Santa Fe presented results of a phase 3 study that randomised 629 treatment naive participants to either B\/F\/TAF or the FDC dolutegravir\/3TC\/abacavir. [1]<\/p>\n

Entry criteria included being HBV negative and B-5701 negative and having eGFR \u226550 mL\/min.<\/p>\n

Baseline characteristics included median age 32 years (IQR 18 to 71), 90% men: 10% women, 45% Caucasian, 36% black, 20% Hispanic\/Latino.<\/p>\n

Median CD4 count and viral load was 444 cells\/mm3<\/sup> (IQR 299 to 608), and 4.5 log copies\/mL (IQR 4.0 to 4.9) respectively, with 11% of participants having CD4 <200 cells\/mm3<\/sup> and 16% with viral load >100,000 copies\/mL. Median eGFR was 123 mL\/min (IQR 107 to 146).<\/p>\n

At week 48, the primary endpoint of viral load <50 copies\/mL was reported in 92.4% vs 93.0% participants in the bictegravir vs dolutegravir groups (difference \u20130.6; 95%CI: \u20134.8 to +3.6, p=0.78) finding non-inferiority for the bictegravir FDC. Similar responses were seen in sensitivity analyses and for CD4 responses.<\/p>\n

Side effects were similar between groups: diarrhoea (13% vs 13%), headache (11% vs 14%), and nausea (10% vs 23%) in the bictegravir vs dolutegravir FDCs respectively. Few people (n=0 vs 4) discontinued due to side effects.<\/p>\n

Other side effects were also similar. The mean percentage changes in bone mineral density (BMD) in lumber spine and total hip were \u20130.83% vs \u20130.60% (p=0.39) and \u20130.78% vs. \u20131.02% (p=0.23) respectively. There were no differences between treatments for eGFR or proteinuria. There were modest increases in all lipids, including HDL, but no differences between groups.<\/p>\n

Bictegravir FDC compared to dolutegravir plus FTC\/TAF<\/h2>\n

The second study included 48-week results from a phase 3 study with dolutegravir plus FTC\/TAF as background NRTIs, presented as a poster by Paul Sax from Brigham and Women’s Hospital, Boston. [2]<\/p>\n

This blinded placebo-controlled study randomised 645 treatment-naive participants with eGFR \u226530 mL\/min to either B\/F\/TAF (50\/200\/25 mg) or dolutegravir (50 mg) plus separate F\/TAF (200\/25 mg) each with matching placebos. All regimens\u00a0are once-daily.<\/p>\n

Baseline characteristics included median age 34 years, 12% women and 31% black. Median CD4 and viral load were 440 cells\/mm3<\/sup>, and VL 4.4 copies\/mL respectively with 12% CD4 <200 cells\/mm3<\/sup> and 19% viral load >5.0 log copies\/mL.<\/p>\n

At week-48, viral load was <50 copies\/mL in 89.4% vs 92.9% of participants in the bictegravir vs dolutegravir arms respectively (difference \u20133.5%; 95%CI \u20137.9% to +1.0%, p=0.12), showing noninferiority based on lower margin of \u201312%.<\/p>\n

Side effects again were similar in each group: headache (13% vs 12%) and diarrhoea (12% for both) with few discontinuations (n=5 vs 1) and no serious renal events.<\/p>\n

The only other poster about bictegravir was a pharmacokinetic study showing similar drug levels in Japanese compared to Caucasian HIV negative volunteers. [3]<\/p>\n

comment<\/h3>\n

Both study results show that bictegravir is very likely to soon be approved in the B\/F\/TAF formulation.<\/strong><\/p>\n

In high- and middle-income countries where the bictegravir FDC is likely to first be used, access is likely to be dependent on drug pricing, even with the advantage of not requiring\u00a0B*5701 and HBV testing before use.<\/strong><\/p>\n

In low-income countries with access to generic dolutegravir, the generic FDC will be coformulated with F\/TAF rather than abacavir\/3TC.<\/strong><\/p>\n

The bictegravir\u00a0FDC\u00a0was submitted to the FDA in June 2017 and to the EMA in July 2017. The FDA application included a priority review with a decision expected by February 2018. [4]<\/strong><\/p>\n

References<\/p>\n

    \n
  1. Gallant J et al. A phase 3 randomized controlled clinical trial of bictegravir in a fixed dose combination, B\/F\/TAF, vs ABC\/DTG\/3TC in treatment-na\u00efve adults at week 48. IAS 2017, Paris. Late breaker oral abstract MOAB0105LB.
    \nhttp:\/\/programme.ias2017.org\/Abstract\/Abstract\/5783<\/a><\/li>\n
  2. Sax P et al. Phase 3 randomized, controlled clinical trial of bictegravir coformulated with FTC\/TAF in a fixed-dose combination (B\/F\/TAF) vs dolutegravir (DTG) + F\/TAF in treatment-na\u00efve HIV-1 positive adults: week 48 results. IAS 2017, Paris. Late breaker poster abstract TUPDB0201LB.
    \n    http:\/\/programme.ias2017.org\/Abstract\/Abstract\/5793<\/a><\/li>\n
  3. Custodio J et al.\u00a0A study evaluating the pharmacokinetics, safety, and tolerability of the bictegravir\/emtricitabine\/tenofovir alafenamide (B\/F\/TAF) single tablet regimen (STR) in Japanese subjects.\u00a0IAS 2017, Paris. Poster abstract MOPEB0332.
    \nhttp:\/\/programme.ias2017.org\/Abstract\/Abstract\/2777<\/a><\/li>\n
  4. Gilead press statement.\u00a0Gilead announces U.S. FDA priority review designation for fixed-dose combination of bictegravir, emtricitabine and tenofovir alafenamide for treatment of HIV. (10 August 2017).
    \n    http:\/\/www.gilead.com\/news\/press-releases<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Simon Collins, HIV i-Base Results from two phase 3 studies were presented at IAS 2017 on bictegravir, a new integrase inhibitor that is coformulated in a fixed dose combination (FDC) with FTC\/TAF. Bictegravir has already been submitted to the FDA …<\/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":[243],"class_list":["post-32149","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-ias-9-paris-2017"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/32149","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=32149"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/32149\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=32149"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=32149"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=32149"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}