Mer­ck hits the brakes on de­vel­op­ment pro­gram as safe­ty fears trig­ger alarm

In a sur­prise set­back, Mer­ck has slammed the brakes on the de­vel­op­ment of an ex­per­i­men­tal HIV drug — in­clud­ing a Phase II tri­al — af­ter in­ves­ti­ga­tors flagged a drop in im­mune cell counts that an ex­ter­nal com­mit­tee de­ter­mined was re­lat­ed to treat­ment.

The Phase II study that first sound­ed the alarm, dubbed IMAG­INE-DR, was test­ing the once-week­ly com­bi­na­tion of MK-8507 (a non-nu­cle­o­side re­verse tran­scrip­tase in­hibitor) and is­la­travir, or ISL, a nu­cle­o­side re­verse tran­scrip­tase translo­ca­tion in­hibitor.

Where­as Mer­ck is paus­ing all pro­grams in­volv­ing MK-8507, the com­pa­ny says it “re­mains con­fi­dent in is­la­travir’s over­all pro­file” and will car­ry on with it.

For Mizuho an­a­lyst Mara Gold­stein, that of­fers a glass half full sit­u­a­tion.

“MRK’s lead an­ti-HIV can­di­date is is­la­travir (ISL), which we see as undis­turbed at this point,” she wrote. “Based on a larg­er body of clin­i­cal da­ta for ISL’s an­ti-HIV ef­fi­ca­cy in­clud­ing the re­cent pos­i­tive top-line up­date (see NOTE), we are not fore­cast­ing changes in the broad­er ISL-based HIV stud­ies, and our mod­el re­mains the same.”

Is­la­travir is al­so one of the two cen­ter­pieces of Mer­ck and Gilead’s joint ef­fort to de­vel­op a long-act­ing HIV ther­a­py, along­side Gilead’s cap­sid in­hibitor lenaca­pavir.

Joan But­ter­ton

Joan But­ter­ton, VP of in­fec­tious dis­eases glob­al clin­i­cal de­vel­op­ment at Mer­ck Re­search Lab­o­ra­to­ries, not­ed Mer­ck re­mains “res­olute” in its pledge to help end the HIV pan­dem­ic and high­light­ed that all clin­i­cal stud­ies pro­vide im­por­tant “learn­ings.”

In IMAG­INE-DR, study par­tic­i­pants ran­dom­ized to re­ceive ISL+MK-8507 saw a de­crease in to­tal lym­pho­cyte and CD4+ T cell counts. The great­est drops were ob­served in the arms of the study re­ceiv­ing the high­est dos­es of MK-8507, name­ly 200 mg and 400 mg.

The ex­ter­nal da­ta mon­i­tor­ing com­mit­tee con­clud­ed that the ad­verse ef­fect had to do with the treat­ment and rec­om­mend­ed stop­ping the tri­al. Mer­ck oblig­ed, and re­viewed all of its tri­als in­volv­ing ISL with a spe­cial eye to those met­rics.

Here’s what they found:

  • The on­go­ing Phase II tri­al (MK-8591-016) is eval­u­at­ing month­ly ISL for PrEP in par­tic­i­pants with low risk of HIV-1 in­fec­tion. Among this un­in­fect­ed group, there was a dose-de­pen­dent de­crease in lym­pho­cyte counts but mean de­creas­es were in the nor­mal range, and there was no in­crease in clin­i­cal ad­verse events re­lat­ed to in­fec­tion.
  • IL­LU­MI­NATE SWITCH A and IL­LU­MI­NATE SWITCH B (MK-8591A-017 and MK-8591A-018) are two Phase III tri­als eval­u­at­ing do­ravirine in com­bi­na­tion with ISL dai­ly (DOR/ISL) in HIV-1 vi­ro­log­i­cal­ly sup­pressed par­tic­i­pants. Here, Mer­ck found a small, treat­ment re­lat­ed mean de­crease in CD4+ T cell counts through week 48, but no in­creased in­ci­dence of AEs re­lat­ed to in­fec­tion.

Mer­ck re­cent­ly re­port­ed pos­i­tive da­ta from the IL­LU­MI­NATE stud­ies, sug­gest­ing the DOR/ISL com­bo has com­pa­ra­ble ef­fi­ca­cy as ex­ist­ing an­ti­retro­vi­ral ther­a­pies.

“In­ves­ti­ga­tors for these tri­als have been in­formed and the tri­als are con­tin­u­ing,” the com­pa­ny wrote.

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His­toric drug pric­ing re­forms pass; Pfiz­er ac­quires GBT; The long search for non-opi­oid pain drugs; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

The Endpoints Weekly has officially crossed the 60,000 mark on subscribers — thanks to all of your support. As the editorial team grows, we’ve been able to do a lot more, with many of those on display this week. Be sure to check out Lei Lei Wu’s deep dive on pain R&D. If you missed it, you may also rewatch her companion panel here.

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Gold for adults, sil­ver for in­fants: Pfiz­er's Pre­vnar 2.0 head­ed to FDA months af­ter Mer­ck­'s green light

Pfizer was first to the finish line for the next-gen pneumococcal vaccine in adults, but Merck beat its rival with a jab for children in June.

Now, two months after Merck’s 15-valent Vaxneuvance won the FDA stamp of approval for kids, Pfizer is out with some late-stage data on its 20-valent shot for infants.

Known as Prevnar 20 for adults, Pfizer’s 20vPnC will head to the FDA by the end of this year for an approval request in infants, the Big Pharma said Friday morning. Discussions with the FDA will occur first and more late-stage pediatric trials are expected to read out soon, informing the regulatory pathway in other countries and regions.

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No­var­tis re­ports two pa­tient deaths af­ter treat­ment with Zol­gens­ma

Two children with spinal muscular atrophy have died after receiving Novartis’ Zolgensma, a gene therapy designed as a one-time treatment for the rare fatal disease.

The deaths, which resulted from acute liver failure, occurred in Russia and Kazakhstan, Novartis confirmed in a statement to Endpoints News. Having notified health authorities across all the markets where Zolgensma is available, it will update the drug label “to specify that fatal acute liver failure has been reported,” a spokesperson wrote.

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House pass­es his­toric drug pric­ing re­forms, lin­ing up decades-in-the-mak­ing win for Biden and De­moc­rats

The US House of Representatives today voted along party lines (all Dems voted for it), 220-207 to pass new, wide-ranging legislation that will allow Medicare drug price negotiations for the first time ever, and cap seniors’ drug expenses to $2,000 per year and seniors’ insulin costs at $35 per month.

Setting up a major victory for President Joe Biden, representatives returned from their summer recess to pass the Inflation Reduction Act, even as many noted the bill would only modestly reduce inflation.

Senate Finance Committee Chair Ron Wyden (D-OR) (Francis Chung/E&E News/POLITICO via AP Images)

Sen­ate Fi­nance chair con­tin­ues his in­ves­ti­ga­tion in­to phar­ma tax­es with re­quests for Am­gen

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

FDA ap­proves sec­ond in­di­ca­tion for As­traZeneca and Dai­ichi's En­her­tu in less than a week

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu scored its second approval in less than a week, this time for a subset of lung cancer patients.

Enhertu received accelerated approval on Thursday to treat adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have already received a prior systemic therapy.

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J&J to re­move talc prod­ucts from shelves world­wide, re­plac­ing with corn­starch-based port­fo­lio

After controversially spinning out its talc liabilities and filing for bankruptcy in an attempt to settle 38,000 lawsuits, Johnson & Johnson is now changing up the formula for its baby powder products.

J&J is beginning the transition to an all cornstarch-based baby powder portfolio, the pharma giant announced on Thursday — just months after a federal judge ruled in favor of its “Texas two-step” bankruptcy to settle allegations that its talc products contained asbestos and caused cancer. An appeals court has since agreed to revisit that case.

CSL is gathering its four business units under a unified brand identity strategy (Credit: CSL company site)

CSL brings Se­qirus, Vi­for un­der par­ent um­brel­la brand in iden­ti­ty re­vamp

CSL is gathering its brands under the family name umbrella, renaming its vaccine and newly acquired nephrology specialty businesses with the parent initials.

CSL Seqirus and CSL Vifor join CSL Plasma and CSL Behring as the four now uniformly branded business units of the global biopharma. The Seqirus vaccine division was formed in 2015 with the combination of bioCSL and its purchase of Novartis’ flu vaccine business. CSL picked up Vifor Pharma late last year in an $11.7 billion deal for the nephrology, iron deficiency and cardio-renal drug developer.

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