{"id":43591,"date":"2022-08-03T07:43:06","date_gmt":"2022-08-03T07:43:06","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=43591"},"modified":"2022-09-12T07:13:13","modified_gmt":"2022-09-12T07:13:13","slug":"simplifed-lenacapavir-dosing-pk-results-in-hiv-negative-study","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/43591","title":{"rendered":"Simplifed lenacapavir dosing: PK results in HIV negative study"},"content":{"rendered":"
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Kirk Taylor, HIV i-Base<\/strong><\/p>\n<\/div>\n

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\"\"<\/strong>AIDS 2022 included a pharmacokinetic (PK) study of a simplified dosing strategy for the long-acting capsid inhibitor lenacapavir, currently being studied for both treatment and prevention. [1]<\/span><\/b><\/p>\n<\/div>\n

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If confirmed, the new strategy could help adherence and reduce the number of clinic visits. <\/span><\/b><\/p>\n<\/div>\n

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This phase 1 open-label study of HIV negative participants explored PK profiles from standard and simplified dosing strategies. <\/span><\/p>\n<\/div>\n

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Group 1 (n=31) received the current three oral lead-in doses (600 mg on days 1 and 2, and 300 mg on day 8) before a sub-cutaneous (SC) injection (927 mg) on day 15. <\/span><\/p>\n<\/div>\n

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Group 2 (n=14) used a simplified strategy with oral (600 mg) plus SC (927 mg) lenacapavir on day 1, followed by a second oral dose (600 mg) on day 2.<\/span><\/p>\n<\/div>\n

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PK parameters were monitored from pre-dose to day 197. The target plasma concentration was 15.5 ng\/mL, equivalent to 4x the protein adjusted IC90. <\/span><\/p>\n<\/div>\n

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Mean plasma levels for group 1 were consistently above the target from 2 hours post-dose on day 2 until the final measurement on day 197. Tmax was reached 85 days post-SC injection.<\/span><\/p>\n<\/div>\n

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Similar PK parameters were observed for the simplified regimen with concentrations consistently above the target from 2 hours post-dose on day 2 and an earlier Tmax at 70 days. However, the lower bound of the 95% CI dipped below the 4x pa IC90 threshold between days 168 and 182.<\/span><\/p>\n<\/div>\n

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Participants were similar in each group, with median age about 32 years (range: 20 to 45) and median BMI was 26 kg\/m2<\/sup> (range: 22 to 30). <\/span><\/p>\n<\/div>\n

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Adverse events were grade 1-2, mostly due to injection site reactions.<\/span><\/p>\n<\/div>\n

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comment<\/span><\/h3>\n<\/div>\n

In HIV negative participants these PK profiles were comparable for <\/span><\/b>simplified and standard dosing and remain above target levels for much of the study. <\/b><\/p>\n

Median plasma concentrations remained above the 4x pa IC90 at all timepoints but results will need to be confirmed in people living with HIV as 90%CI dropped below this level with the simplified strategy. The lower levels between days 168 to 182 may be explained by the relatively low sample size (n=14) for group 2.<\/b><\/p>\n

Lenacapavir has already been submitted to the EMA and US FDA for an indication in multidrug resistant HIV.<\/strong><\/p>\n

In July 2022, the EMA reported a positive recommendation for approval.<\/strong><\/p>\n

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References<\/span><\/p>\n<\/div>\n

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1. \u00a0\u00a0\u00a0 Jogiraju V et al. Pharmacokinetics of a simplified subcutaneous lenacapavir regimen versus phase 2\/3 regimen. AIDS 2022 (Montreal). 29th July to 2nd August. Abstract PESUB22.<\/span><\/p>\n<\/div>\n

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https:\/\/programme.aids2022.org\/Abstract\/Abstract\/?abstractid=5490<\/a> (abstract)<\/span><\/p>\n<\/div>\n

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https:\/\/conference.aids2022.org\/media-2508-pharmacokinetics-of-a-simplified-subcutaneous-lenacapavir-regimen-versus-phase-2-3-regimen<\/a> (e-poster)<\/span><\/p>\n<\/div>\n

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2.\u00a0\u00a0\u00a0\u00a0 Lenacapavir gets positive opinion for approval in the EU to treat MDR HIV. HTB (July 2022)<\/span><\/p>\n<\/div>\n

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https:\/\/i-base.info\/htb\/43197<\/span><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Kirk Taylor, HIV i-Base AIDS 2022 included a pharmacokinetic (PK) study of a simplified dosing strategy for the long-acting capsid inhibitor lenacapavir, currently being studied for both treatment and prevention. [1] If confirmed, the new strategy could help adherence and …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3,34],"tags":[],"class_list":["post-43591","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","category-pk-and-drug-interactions"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/43591","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=43591"}],"version-history":[{"count":1,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/43591\/revisions"}],"predecessor-version":[{"id":44007,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/43591\/revisions\/44007"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=43591"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=43591"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=43591"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}