{"id":42313,"date":"2022-03-01T07:41:10","date_gmt":"2022-03-01T07:41:10","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=42313"},"modified":"2022-09-12T07:45:12","modified_gmt":"2022-09-12T07:45:12","slug":"lenacapavir-54-week-results-in-treatment-naive-participants-of-calibrate-study","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/42313","title":{"rendered":"CROI 2022: Lenacapavir: 54 week results in treatment-naive participants of CALIBRATE study"},"content":{"rendered":"
<\/div>\n
\n

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

\n

\"CROISamir Gupta from Indiana University presented 54-week results on the capsid inhibitor lenacapavir in 182 treatment-naive individuals in the randomised phase 2 CALIBRATE study. [1]<\/span><\/strong><\/p>\n<\/div>\n

\n

The study design included randomisation to one of four open-label once-daily groups (2:2:2:1), with differences in the three maintenance combinations at week 28 (Q6M LEN injections +TAF, Q6M LEN injections + bictegravir or oral LEN+F\/TAF) compared to a control group of bictegravir\/F\/TAF (n=25); groups 1, 2, 3, and 4 respectively). [2]<\/p>\n<\/div>\n

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Interim results were reported at IAS last year [3] and 92% of participants subsequently achieved viral suppression at week 28.<\/p>\n<\/div>\n

\n

Baseline characteristics previously reported included median age 29 years (range: 19 to 72), 93% men (7% women), 52% black, 45% Hispanic\/Latinx. Median viral load and CD4 count at baseline were 4.3 log copies\/mL (IQR: 3.8 to 4.7) with 15% >100,000 c\/mL and 437 cells\/mm3 <\/sup>(IQR: 332 to 599), with only two participants <200 cells\/mm3<\/sup>.<\/span><\/p>\n<\/div>\n

\n

The primary endpoint of viral efficacy (<50 copies\/mL) was reported for\u00a0 90%, 85%, 85% and 92% for <\/span>groups 1, 2, 3, and 4 respectively. Viral failure was reported for 4%, 4%, 6% and 0 of the same groups, with remaining participants having missing data.<\/p>\n<\/div>\n

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Six participants met criteria for resistance testing (1, 1, 3 and 1 in groups 1 to 4 respectively), two with resistance to lenacapavir. One participant in group 2 developed Q57H + K70R in capsid at week 10 (20-fold resistance) and one in group 3 developed Q57H alone at week 54 (7-fold). Both were reported in the context of likely low adherence to oral ART and both resuppressed using combinations of an INSTI and two NRTIs.<\/p>\n<\/div>\n

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Lenacapavir generated similar early rapid viral suppression as the integrase inhibitor-based control group. Minimal data was provided on CD4 count other than similar average increases of about 200 cells\/mm3<\/sup> in each arm.<\/p>\n<\/div>\n

\n

Tolerability was generally good and similar to oral control with headache 13% vs 12%, nausea 13% vs 4% and COVID-19 10% vs 12%, all in combined LEN vs control, respectively. There were no serious AE’s related to lenacapavir, or discontinuations, other than to injection site reactions (ISRs).<\/p>\n<\/div>\n

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ISRs were common (approximately 15% after injection 1 and 12% after injection 2, but were mainly grade 1 or 2 and caused only three participants to discontinue (all grade 1). However, nodules or hard skin persisted for over six months (median 195 and 202 days for nodules and induration respectively).<\/p>\n<\/div>\n

\n

There were no clinically relevant or grade 3\/4 lab abnormalities.<\/p>\n<\/div>\n

\n

Other studies on lenacapavir including Week 48 results in treatment experienced participants in the CAPELLA study and use as PrEP are reported in a separate HTB report. [3]<\/span><\/p>\n

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

Lenacapavir is currently on clinical hold related to a technical concern about glass vials used in these studies. <\/span><\/strong><\/p>\n

A press statement from Gilead outlines further details to resolve this. [5]<\/span><\/strong><\/p>\n<\/div>\n<\/div>\n

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

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    \n
  1. Gupta S et al. Lenacapavir as part of a combination regimen in treatment naive PWH: week 54 results. CROI 2022. 12-16 February 2022, virtual. Oral abstract 138.
    \n<\/span>https:\/\/www.croiconference.org\/abstract\/lenacapavir-as-part-of-a-combination-regimen-in-treatment-naive-pwh-week-54-results<\/a><\/li>\n
  2. ClinicalTrials.gov. Study to evaluate the safety and efficacy of lenacapavir in combination with other antiretroviral agents in people living with HIV (CALIBRATE).
    \n    https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04143594<\/a><\/li>\n
  3. IAS 2021: lenacapavir studies show impressive results in naive, extensive drug resistance and potential as PrEP. IAS 2021 reports. HTB (1 August 2021).
    \n    https:\/\/i-base.info\/htb\/41003<\/a><\/li>\n
  4. Lenacapavir at CROI 2022: 6-monthly dosing in treatment-experienced participants, and as PrEP in macaques. CROI 2022 reports. HTB (1 March 2022).
    \n    https:\/\/i-base.info\/htb\/42123\u00a0<\/a><\/li>\n
  5. Gilead press statement. Gilead receives complete response letter from US FDA for investigational lenacapavir due to vial compatability issues. (1 March 2022).
    \n    https:\/\/www.gilead.com\/news-and-press\/press-room\/press-releases\/2022\/3\/gilead-receives-complete-response-letter-from-us-fda-for-investigational-lenacapavir-due-to-vial-compatability-issues<\/a><\/li>\n<\/ol>\n

    This report was first published on 19 February 2022.<\/em><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

    Simon Collins, HIV i-Base Samir Gupta from Indiana University presented 54-week results on the capsid inhibitor lenacapavir in 182 treatment-naive individuals in the randomised phase 2 CALIBRATE study. [1] The study design included randomisation to one of four open-label once-daily …<\/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":[318],"class_list":["post-42313","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-croi-2022"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/42313","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=42313"}],"version-history":[{"count":1,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/42313\/revisions"}],"predecessor-version":[{"id":44069,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/42313\/revisions\/44069"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=42313"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=42313"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=42313"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}