{"id":44724,"date":"2023-02-01T07:39:52","date_gmt":"2023-02-01T07:39:52","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=44724"},"modified":"2023-04-10T18:44:12","modified_gmt":"2023-04-10T18:44:12","slug":"pipeline-studies-at-glasgow-2022","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/44724","title":{"rendered":"Glasgow 2022: pipeline studies with bNAbs N6LS and maturation inhibitor GSK254"},"content":{"rendered":"

Kirk Taylor, HIV i-Base<\/strong><\/p>\n

\"\"<\/a>Glasgow 2022 included new results on two pipeline compounds: N6LS and GSK254.<\/span><\/strong><\/div>\n

Phase 2 results from the BANNER study support antiviral activity of N6LS bNAbs in ART-na\u00efve people living with HIV. Viral nadir occurred after 16 days, and post-infusion and viral rebound occurred after a median of 35 days. [1]<\/p>\n

A novel maturation inhibitor (GSK3640254) has been associated with QT prolongation in pre-clinical models. New data indicate that plasma levels below 3 \u00b5g\/mL do not significantly alter QT interval in HIV negative participants. [2]<\/p>\n

Broadly neutralising antibodies (bNAbs)<\/h2>\n

ViiV Healthcare are developing VH3810109 (N6LS) as a bNAb therapy that targets the CD4 binding site of the HIV envelope protein. [1]<\/p>\n

BANNER is an open-label, single dose phase 2 study evaluating the antiviral efficacy of N6LS monotherapy in treatment na\u00efve people living with HIV.<\/p>\n

Participants were randomised to receive either a 40 mg\/kg (group 1, n=8) or 4 mg\/kg (group 2, n=6) infusion of N6LS. Whilst baseline CD4 counts and BMI were comparable between groups, baseline viral load was higher in group 2 [30,833 copies\/mL (IQR: 5,938 to 104,585) vs 12,259 copies\/mL (IQR: 1,351 to 173,710)].<\/p>\n

A single bNAb infusion decreased viral load by a median of 1.72 log10 copies\/mL (IQR: -0.60 to -2.60) for 13\/14 participants. Median response time was 16 days (IQR: 5 to 21) and viral rebound was observed after 35 days (range: 12 to 78). All drug-related adverse events (n=9) were \u2264grade 2.<\/p>\n

Participants were recruited from the USA (n=6), Canada (n=1) and Argentina (n=7) and were male (n=13\/14), Black (n=3), White (n=11) and Latinx (n=10). Median age was 30.5 years (IQR: 24 to 51) and 28.0 years (IQR: 18 to 54) in groups 1 and 2, respectively.<\/p>\n

Maturation inhibitor GSK3640254<\/h2>\n

GSK are developing a novel maturation inhibitor (GSK3640254) for HIV treatment. Pre-clinical testing identified QT prolongation following administration of a supramaximal dose of 17 mg\/kg (Cmax = 7,960 ng\/mL). Palpitations were also reported in a HIV negative participant that received a single 200 mg oral dose.<\/p>\n

A two-part study was conducted to evaluate cardiac effects of the maturation inhibitor in HIV negative participants. [2]<\/p>\n

Participants were female (30%), Black (40%) and mean age was 34 years. In part one 8 participants were randomised (3:1) to 500 mg GSK3640254 or placebo for 7 days. For part two, 42 participants were randomised to 12 treatment sequences to compare intended therapeutic (100 mg) and supratherapeutic doses (500 mg) of maturation inhibitor, a single dose of moxifloxacin (400mg) and placebo control.<\/p>\n

Cmax levels of the maturation inhibitor were 830 ng\/mL (95% CI: 738 to 934 ng\/mL) for a 100 mg dose and 4,260 ng\/mL (95% CI: 3,750 to 4,840 ng\/mL) following a 500 mg dose, respectively. A dose-dependent increase in QT interval was observed. QT prolongation is predicted to be <10 ms when plasma levels of the maturation inhibitor are below 3,070 ng\/mL. Participants that received 100 mg doses had QT prolongation of 2.72 ms (90% CI: 2.04 to 3.39 ms). Low grade (\u22641) adverse events were reported by participants in part one (38%) and part two (43%). Phase 2 trials are continuing with doses that are predicted to not significantly impact QT interval (100 to 200 mg).<\/p>\n

References<\/p>\n

Please notes that due to earlier website problems on the conference website, links below are to NATAP.org. The resolved link to the conference posters is now:
\nhttps:\/\/www.hivglasgow.org\/2022-posters<\/a><\/p>\n

    \n
  1. Leone P et al. VH3810109 (N6LS) reduces viremia across a range of doses in ART-na\u00efve adults living with HIV: Proof of concept achieved in the phase IIa BANNER (207959, NCT04871113) study. HIV Drug Therapy Glasgow, October 23-26, 2022. Oral abstract O34..
    \n    https:\/\/www.natap.org\/2022\/Glascow\/GLASGOW_50.htm<\/a><\/li>\n
  2. Zhang Y et al. Effects of the HIV-1 maturation inhibitor GSK3640254 on QT interval in healthy participants. HIV Drug Therapy Glasgow, October 23-26, 2022. Poster abstract P210.
    \n    https:\/\/hivglasgow.org\/wp-content\/uploads\/2023\/01\/P210_Wynne_Brian.pdf<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Kirk Taylor, HIV i-Base Glasgow 2022 included new results on two pipeline compounds: N6LS and GSK254. Phase 2 results from the BANNER study support antiviral activity of N6LS bNAbs in ART-na\u00efve people living with HIV. Viral nadir occurred after 16 …<\/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":[325],"class_list":["post-44724","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-hiv-16-glasgow-2022"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/44724","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=44724"}],"version-history":[{"count":9,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/44724\/revisions"}],"predecessor-version":[{"id":45244,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/44724\/revisions\/45244"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=44724"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=44724"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=44724"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}