FDA ad­comm nar­row­ly votes in fa­vor of Mer­ck­'s an­tivi­ral for out­pa­tient Covid-19

With lit­tle ex­pla­na­tion for why Mer­ck’s po­ten­tial Covid-19 an­tivi­ral was less ef­fec­tive in re­duc­ing Covid hos­pi­tal­iza­tions and deaths in a full analy­sis of a Phase III tri­al ver­sus an in­ter­im look, the FDA’s an­timi­cro­bial drugs ad­vi­so­ry com­mit­tee on Tues­day vot­ed 13-10 in fa­vor of the pill’s ben­e­fits out­weigh­ing the risks for adults with­in 5 days of de­vel­op­ing Covid symp­toms.

Mol­nupi­ravir will like­ly be au­tho­rized by FDA in the com­ing days for adults with mild or mod­er­ate Covid-19. While Pfiz­er’s an­tivi­ral may prove to be more ef­fec­tive, Mer­ck’s pill will be an­oth­er weapon in the ar­ma­men­tar­i­um of Covid-19 treat­ments for coun­tries around the world, adding to the mAb treat­ments al­ready in use in the out­pa­tient space from Re­gen­eron, Eli Lil­ly and Vir/Glax­o­SmithK­line.

Ad­comm mem­ber David Hardy of the Charles Drew Uni­ver­si­ty School of Med­i­cine and Sci­ence said he vot­ed “yes” be­cause the pan­dem­ic is still an emer­gency sit­u­a­tion, and this is the first op­por­tu­ni­ty for an oral drug to be avail­able. There needs to be a warn­ing about us­ing this drug in preg­nant women, he said, not­ing of the po­ten­tial for fe­tal ab­nor­mal­i­ties.

Pan­elist Tim­o­thy Burgess of the Uni­formed Ser­vices Uni­ver­si­ty of the Health Sci­ences said he vot­ed “no” on the ba­sis of the very dif­fi­cult to ex­plain dif­fer­ences in the pop­u­la­tion be­fore and af­ter the in­ter­im analy­sis (see be­low), and the het­ero­gene­ity of the ben­e­fit, par­tic­u­lar­ly for those with di­a­betes.

Dur­ing the dis­cus­sion por­tion of the ad­comm, pan­elists cen­tered their ques­tion­ing on the Mer­ck pill’s ef­fi­ca­cy and the cause of this drop off in pre­vent­ing hos­pi­tal­iza­tions and deaths, from 50% to 30% be­tween in­ter­im and fi­nal re­sults. Nei­ther Mer­ck nor the FDA could re­al­ly of­fer any spe­cif­ic caus­es. Sub­group analy­ses seem to sug­gest that mol­nupi­ravir did bet­ter against the Gam­ma and Mu vari­ants than the Delta vari­ant, but that doesn’t ex­plain how steeply the ef­fi­ca­cy fell.

For in­stance, in the post-in­ter­im analy­sis pop­u­la­tion, FDA showed how there were more Covid-re­lat­ed hos­pi­tal­iza­tions among tri­al par­tic­i­pants re­ceiv­ing mol­nupi­ravir com­pared to those re­ceiv­ing place­bo.

“It doesn’t re­al­ly add up to us,” Nicholas Kart­so­nis, SVP of clin­i­cal re­search, in­fec­tious dis­eases at Mer­ck, said. He not­ed that the com­pa­ny ex­pect­ed some re­gres­sion to the mean with the lat­er da­ta, but not this kind of re­duc­tion in ben­e­fit.

He point­ed to sev­er­al po­ten­tial fac­tors, in­clud­ing the rise of Delta, more fe­male tri­al par­tic­i­pants who are less like­ly than their male coun­ter­parts to be hos­pi­tal­ized or die of Covid, and more par­tic­i­pants in Eu­rope in the sec­ond part of the tri­al. “I don’t have a sat­is­fy­ing an­swer but that’s the to­tal­i­ty of da­ta,” Kart­so­nis said.

When FDA sought to di­rect the con­ver­sa­tion to ques­tions about the ef­fi­ca­cy of mol­nupi­ravir in preg­nant women, sev­er­al pan­elists al­so ques­tioned the ef­fi­ca­cy in adults in gen­er­al.

“We’re skirt­ing the is­sue of is there a ben­e­fit of the med­ica­tion in adults,” said ad­comm pan­elist Uma Red­dy, who’s an OBG­YN at Yale.

Pan­elist Michael Green, pro­fes­sor of the Uni­ver­si­ty of Pitts­burgh School of Med­i­cine, vot­ed in fa­vor of the pill’s ben­e­fits and not­ed the lack of avail­abil­i­ty of an al­ter­na­tive oral treat­ment for un­vac­ci­nat­ed peo­ple, and the po­ten­tial loss of mAbs due to the new vari­ant Omi­cron, which Mer­ck said it thinks the an­tivi­ral will be ef­fec­tive against. “Should an al­ter­na­tive oral drug with a bet­ter safe­ty pro­file, the agency might con­sid­er this au­tho­riza­tion,” Green said.

An­oth­er is­sue for the ad­comm mem­bers is the way that mol­nupi­ravir works, which is to dri­ve the mu­ta­ge­n­e­sis of the SARS-COV-2 virus to kill it off, and which could the­o­ret­i­cal­ly in­crease the like­li­hood of vari­ants oc­cur­ring as a re­sult of wide­spread treat­ment. But the FDA not­ed in its pre­sen­ta­tion that there’s no ev­i­dence that the emer­gence of spike pro­tein amino acid changes af­fect­ed vi­ro­log­ic or clin­i­cal out­comes in out­pa­tients.

Kart­so­nis said Mer­ck will be strong­ly rec­om­mend­ing that peo­ple com­plete their 5-day treat­ment cours­es to avoid any the­o­ret­i­cal con­cerns.

“We are ex­plor­ing the fea­si­bil­i­ty of us­ing se­quence data­bas­es to mon­i­tor for the emer­gence of these nov­el vari­ants,” Kart­so­nis added. “To date, if you treat peo­ple for 5 days, we’ve yet to iden­ti­fy a sin­gle case of in­fec­tious virus at day 5, so that’s a very pos­i­tive sign.”

Sev­er­al pan­elists al­so said they thought the risk for the gen­er­al pub­lic is low com­pared to the sub­stan­tial amount of nat­ur­al mu­ta­tions, but a few did raise con­cerns, par­tic­u­lar­ly if mil­lions of peo­ple ac­cess the drug.

The over­all thumbs up from the pan­el is based on re­sults from a Phase III tri­al of about 1,500 un­vac­ci­nat­ed adults, find­ing 68 hos­pi­tal­iza­tions and 9 deaths in the place­bo group, com­pared to 48 hos­pi­tal­iza­tions and one death for those on the Mer­ck pill.

The FDA said in its analy­sis of Mer­ck’s da­ta that the pill is safe and re­duces the risk of hos­pi­tal­iza­tion or death among adults with mild to mod­er­ate Covid-19 and who are at high-risk for pro­gres­sion to se­vere Covid. Sim­i­lar to the UK, the FDA is not like­ly to rec­om­mend the pill for preg­nant women due to the po­ten­tial of em­bryo-fe­tal tox­i­c­i­ty.

The US has now pur­chased more than 3 mil­lion cours­es of the Covid-19 an­tivi­ral, to be ac­quired from au­tho­riza­tion through ear­ly 2022, Mer­ck said. The con­tracts have earned Mer­ck a cool $2.2 bil­lion so far, and there are two mil­lion cours­es avail­able through fur­ther op­tions.

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.

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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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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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Alexander Lefterov/Endpoints News

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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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.

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Pfizer and BioNTech announced Tuesday that they’ve initiated a clinical study to evaluate the safety, tolerability and immunogenicity of an Omicron-targeted vaccine candidate in healthy adults 18 through 55 years of age, although it remains unclear when, if ever, that vaccine might be necessary.

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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.

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