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.

Albert Bourla (Photo by Steven Ferdman/Getty Images)

UP­DAT­ED: Pfiz­er fields a CRL for a $295M rare dis­ease play, giv­ing ri­val a big head start

Pfizer won’t be adding a new rare disease drug to the franchise club — for now, anyway.

The pharma giant put out word that their FDA application for the growth hormone therapy somatrogon got the regulatory heave-ho, though they didn’t even hint at a reason for the CRL. Following standard operating procedure, Pfizer said in a terse missive that they would be working with regulators on a followup.

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A new can­cer im­munother­a­py brings cau­tious hope for a field long await­ing the next big break­through

Bob Seibert sat silent across from his daughter at their favorite Spanish restaurant near his home in Charleston County, SC, their paella growing cold as he read through all the places in his body doctors found tumors.

He had texted his wife, a pediatric intensive care nurse, when he got the alert that his online chart was ready. Although he saw immediately it was bad, many of the terms — peritoneal, right iliac — were inscrutable. But she was five hours downstate, at a loud group dinner the night before another daughter’s cheer competition.

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Graphic: Alexander Lefterov for Endpoints News

Small biotechs with big drug am­bi­tions threat­en to up­end the tra­di­tion­al drug launch play­book

Of the countless decisions Vlad Coric had to make as Biohaven’s CEO over the past seven years, there was one that felt particularly nerve-wracking: Instead of selling to a Big Pharma, the company decided it would commercialize its migraine drug itself.

“I remember some investors yelling and pounding on the table like, you can’t do this. What are you thinking? You’re going to get crushed by AbbVie,” he recalled.

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Mar­ket­ingRx roundup: Pfiz­er de­buts Pre­vnar 20 TV ads; Lil­ly gets first FDA 2022 pro­mo slap down let­ter

Pfizer debuted its first TV ad for its Prevnar 20 next-generation pneumococcal pneumonia vaccine. In the 60-second spot, several people (actor portrayals) with their ages listed as 65 or older are shown walking into a clinic as they turn to say they’re getting vaccinated with Prevnar 20 because they’re at risk.

The update to Pfizer’s blockbuster Prevnar 13 vaccine was approved in June, and as its name suggests is a vaccine for 20 serotypes — the original 13 plus seven more that cause pneumococcal disease. Pfizer used to spend heavily on TV ads to promote Prevnar 13 in 2018 and 2019 but cut back its TV budgets in the past two fall and winter seasonal spending cycles. Prevnar had been Pfizer’s top-selling drug, notching sales of just under $6 billion in 2020, and was the world’s top-selling vaccine before the Covid-19 vaccines came to market last year.

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Roy Baynes, Merck

FDA bats back Mer­ck’s ‘pipeline in a prod­uct,’ de­mands more ef­fi­ca­cy da­ta

Despite some heavy blowback from analysts, Merck execs maintained an upbeat attitude about the market potential of its chronic cough drug gefapixant. But the confidence may be fading somewhat today as Merck puts out news that the FDA is handing back its application with a CRL.

Dubbed by Merck’s development chief Roy Baynes as a “pipeline in a product” with a variety of potential uses, Merck had fielded positive late-stage data demonstrating the drug’s ability to combat chronic cough. The drug dramatically reduced chronic cough in Phase III, but so did placebo, leaving Merck’s research team with a marginal success on the p-value side of the equation.

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Florida Gov. Ron DeSantis (AP Photo/Wilfredo Lee, File)

Opin­ion: Flori­da is so mAb crazy, Ron De­San­tis wants to use mAbs that don't work

Florida Gov. Ron DeSantis is trying so hard to politicize the FDA and demonize the federal government that he entered into an alternate universe on Monday evening in describing a recent FDA action to restrict the use of two monoclonal antibody, or mAb, treatments for Covid-19 that don’t work against Omicron.

Without further ado, let’s break down his statement from last night, line by line, adjective by adjective.

Steve Worland, eFFECTOR CEO

Sur­prise piv­ot rocks eF­FEC­TOR's I/O plans — al­though ex­ecs promise big­ger slice of the NSCLC mar­ket in the long run

When eFFECTOR Therapeutics went public last summer on the coattails of a reverse merger with Locust Walk’s SPAC, the potential of its lead drug, tomivosertib, as a combo agent with Merck’s flagship PD-1 Keytruda was hailed as the main draw.

But the biotech is now axing those plans and essentially starting over.

In a surprise move, San Diego-based eFFECTOR said it’s halting the development of tomivosertib in non-small cell lung cancer patients who have already progressed on Keytruda monotherapy after running into enrollment challenges in a Phase IIb trial.

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Not cheap­er by the dozen: Bris­tol My­ers be­comes the 12th phar­ma com­pa­ny to re­strict 340B sales

Bristol Myers Squibb recently joined 11 of its peer pharma companies in limiting how many contract pharmacies can access certain drugs discounted by a federal program known as 340B.

Bristol Myers is just the latest in a series of high-profile pharma companies moving in their own direction as the Biden administration’s Health Resources and Services Administration struggles to rein in the drug discount program for the neediest Americans.

Joaquin Duato, J&J CEO (Photo by Charles Sykes/Invision/AP)

New J&J CEO Joaquin Du­a­to promis­es an ag­gres­sive M&A hunt in quest to grow phar­ma sales

Joaquin Duato stepped away from the sideline and directly into the spotlight on Tuesday, delivering his first quarterly review for J&J as its newly-tapped CEO after an 11-year run in senior posts. And he had some mixed financial news to deliver today while laying claim to a string of blockbuster drugs in the making and outlining an appetite for small and medium-sized M&A deals.

Duato also didn’t exactly shun large buyouts when asked about the future of the company’s medtech business — where they look to be in either the top or number 2 position in every segment they’re in — even though the bar for getting those deals done is so much higher.

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