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.

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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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Seagen interim CEO Roger Dansey and Daiichi Sankyo CEO Sunao Manabe

Paving the way for Mer­ck­'s buy­out, Seagen los­es ar­bi­tra­tion dis­pute with Dai­ichi over ADC tech

As Seagen awaits a final buyout offer from Merck that could be in the territory of $40 billion, Seagen revealed Friday afternoon that it lost an arbitration dispute with Daiichi Sankyo relating to the companies’ 2008 collaboration around the use of antibody-drug conjugate (ADC) technology.

But that loss likely won’t matter much when it comes to Merck’s deal.

After breaking off its pact with Daiichi in mid-2015, the two companies battled over “linker” tech — a chemical bridge between an ADC’s antibody component and the cytotoxic payload — that Seagen claims Daiichi would improve upon and implement in its current generation of ADCs.

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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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Elcin Barker Ergun, Menarini Group CEO

Amid Roche and Sanofi's oral SERD set­backs, Menar­i­ni gets speedy re­view at FDA

Menarini and Radius Health are getting a speedy review at the FDA for their oral SERD breast cancer drug months after the field opened up with competitors failing and fleeing.

It was a one-two-three punch in March, April and May as Sanofi flunked its first big test for its oral selective estrogen receptor degrader (SERD), Roche also flamed out in a Phase II and G1 Therapeutics ended its program after scoping out the data and potential partners.

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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.

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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.

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.