{"id":41647,"date":"2021-11-30T07:33:23","date_gmt":"2021-11-30T07:33:23","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=41647"},"modified":"2021-12-13T22:39:20","modified_gmt":"2021-12-13T22:39:20","slug":"msd-mercks-once-weekly-phase-2-study-stopped-due-to-safety-concerns-with-nnrti-mk-8507-islatravir-studies-continue","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/41647","title":{"rendered":"MSD\/Merck stop once-weekly NNRTI MK-8507: islatravir studies continue with closer monitoring"},"content":{"rendered":"
Simon Collins, HIV i-Base<\/span><\/strong><\/div>\n
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On 18 November 2021, a press release from MSD\/Merck included top line concerns about an investigational NNRTI currently being studied with islatravir as a component of once-weekly oral ART.<\/span><\/strong><\/p>\n<\/div>\n

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The statement reports decreases in total lymphocyte and CD4 counts in participants receiving MK-8507 + islatravir that were dose-related to the NNRTI and were sufficient for dosing to be stopped.<\/span><\/p>\n<\/div>\n

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The press release notes that the company are confident in the profile of islatravir and that both treatment and prevention studies with this compound are continuing. <\/span><\/p>\n<\/div>\n

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However it also reports that a review of other ongoing studies reported small and non-significant mean changes in total lymphocyte counts. This included a decrease <\/span>in HIV negative people using once-monthly islatravir as PrEP at 60 mg and 120 mg that was dose-dependent<\/span>, but that remained within the normal range.<\/p>\n<\/div>\n

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It also included small mean CD4 decreases in two phase 3 switch studies (ILLUMINATE A nd B) – using daily dual ART with doravirine and islatravir (0.75 mg) – both of which are continuing.<\/p>\n<\/div>\n

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The development of MK-8507 is now on hold.<\/span><\/p>\n<\/div>\n

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comment<\/span><\/h3>\n<\/div>\n
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This is very disappointing news.<\/span><\/strong><\/p>\n<\/div>\n

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It shows the difficulties in drug development even after promising compounds have cleared in vitro, animal studies and phase 1 studies.<\/span><\/strong><\/p>\n

A conference call with community advocates shortly after the press release included additional details on these early findings. This included the significance of the mean dose-related reductions in both total lymphocytes and CD4 T cells in the highest dose (400 mg) MK-8507 group. Mean reductions of 17%, 26% and 30% in total lymphocytes and 11%, 23% and 30% in CD4 T cells were seen in the 100 mg, 200 mg and 400 mg MK-8507 groups.<\/strong><\/p>\n

It also included details of reductions in total lymphocyte counts in ongoing islatravir studies. <\/strong><\/p>\n

For example, mean reductions of 21% and 36% were seen in the phase 2 PrEP studies in HIV negative people, at the 60 mg and 120 mg arms monthly dose respectively (vs +4% increase in the placebo group).\u00a0<\/strong><\/p>\n

While mean reductions are still within the normal range, and no individuals went below this range, this might require new entry criteria for these studies.<\/strong><\/p>\n

Although the mean CD4 reductions at week-48 in ongoing\u00a0treatment experienced phase 3 studies using daily islatravir with doravirine are small, larger CD4 reductions have been experienced by a minority of participants.<\/strong><\/p>\n

The company emphasised that these signals are being taken seriously and that participant safety remains central to continued research with all investigational compounds. <\/strong><\/p>\n

No increase in side effects have been reported. Increasing monitoring will be added to all studies in discussion with investigators.<\/strong><\/p>\n<\/div>\n

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

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Merck press release. Merck provides update on phase 2 clinical trial of once-weekly investigational combination of MK-8507 and islatravir for the treatment of people living with HIV-1. (18 November 2021).
\nhttps:\/\/www.merck.com\/news\/merck-provides-update-on-phase-2-clinical-trial-of-once-weekly-investigational-combination-of-mk-8507-and-islatravir-for-the-treatment-of-people-living-with-hiv-1<\/a><\/span><\/p>\n<\/div>\n

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This report was first posted on 19 November 2021, with updated comments and a changed in the title on 24 November 2021.<\/em>\u00a0<\/span><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base On 18 November 2021, a press release from MSD\/Merck included top line concerns about an investigational NNRTI currently being studied with islatravir as a component of once-weekly oral ART. The statement reports decreases in total lymphocyte …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3],"tags":[],"class_list":["post-41647","post","type-post","status-publish","format-standard","hentry","category-antiretrovirals"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/41647","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=41647"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/41647\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=41647"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=41647"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=41647"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}