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.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; 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.

I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

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Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

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Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

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CBER Director Peter Marks (Susan Walsh/AP Images)

FDA ad­vi­so­ry com­mit­tee votes unan­i­mous­ly in fa­vor of bi­va­lent Covid shots re­plac­ing pri­ma­ry se­ries

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all current vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

The vote marks an effort to clear up confusion around varying formulations and dosing schedules for current primary series and booster vaccines, as well as “get closer to the strains that are circulating,” according to committee member Paul Offit, professor of pediatrics at the Children’s Hospital of Philadelphia.

FDA cuts off use for As­traZeneca’s Covid-19 ther­a­py Evusheld

The FDA has stopped use of another drug as a result of the new coronavirus variants. On Thursday, the agency announced that AstraZeneca’s antibody combo Evusheld, which was an important prevention option for many immunocompromised people and others, is no longer authorized.

The FDA said it made its decision based on the fact that Evusheld works on fewer than 10% of circulating variants.

Evusheld was initially given emergency authorization at the end of 2021. However, as Omicron emerged, so did studies that showed Evusheld might not work against the dominant Omicron strain. In October, the FDA warned healthcare providers that Evusheld was useless against the Omicron subvariant BA.4.6. It followed that up with another announcement earlier this month that it did not think Evusheld would work against the latest Omicron subvariant XBB.1.5.

Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

Post-hoc analy­sis: EMA's CHMP re­jects Ipsen's po­ten­tial drug for rare ge­net­ic dis­ease

The European Medicines Agency’s Committee for Medicinal Products for Human Use on Friday rejected Ipsen Pharma’s potential treatment for a rare genetic disease known as fibrodysplasia ossificans progressiva (FOP), which causes extra bone to form outside the skeleton.

The EMA said on its website that it could not draw any firm conclusions on the benefits of the French biopharma’s Sohonos (palovarotene), which selectively targets the retinoic-acid receptor gamma (RARγ), “as the applicant’s conclusion was based on a post-hoc analysis which was neither scientifically nor clinically justified and pre-specified study objectives were not met.”

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FDA ap­proves an­oth­er in­di­ca­tion for Keytru­da, this time in the ad­ju­vant NSCLC set­ting

Merck’s blockbuster cancer treatment Keytruda has been handed another indication by the FDA.

The US regulator announced on Thursday that it has approved Keytruda to serve as an adjuvant treatment for non-small cell lung cancer (NSCLC), which is its fifth indication in NSCLC and 34th indication overall.

According to a Merck release, the approval is based on data from a Phase III trial, dubbed Keynote-091, which measured disease-free survival in patients who received chemotherapy following surgery. The data from Merck displayed that Keytruda cut down on the risk of disease recurrence or death by 27% versus placebo.

Steve Harr, Sana Biotechnology CEO

Four years in, Sana gets first FDA go-ahead to bring can­cer treat­ment in­to the clin­ic

Sana Biotechnology is finally headed to the clinic.

Thursday afternoon, the biotech announced the FDA had cleared its application to start a clinical trial for its allogeneic, or “off-the-shelf,” CAR-T cell therapy targeting the antigen CD19 for patients with B-cell lymphomas and leukemias. Sana said its therapy, dubbed SC291, was designed to evade the immune system, which could help cell therapy produce a more durable response in patients, a concern that has followed such off-the-shelf therapies that use donor cells as opposed to a patient’s own cells.

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