Lex­i­con slams FDA over hear­ing de­nial fol­low­ing a CRL for its SGLT2 in­hibitor can­di­date

Lex­i­con Phar­ma­ceu­ti­cal is not giv­ing up on its Type I di­a­betes can­di­date, de­spite FDA’s re­peat­ed re­jec­tions. This week the com­pa­ny laid out is ar­gu­ment again for a hear­ing on so­tagliflozin in re­sponse to the FDA’s most re­cent de­nial.

The is­sue goes back to March 2019 when the FDA made very clear to Lex­i­con and its now de­part­ed part­ner Sanofi that it would not ap­prove their ap­pli­ca­tion for a po­ten­tial Type I di­a­betes drug be­cause it does not ap­pear to be safe.

“The da­ta demon­strat­ed that the ad­di­tion of so­tagliflozin to in­sulin is as­so­ci­at­ed with an in­creased risk of di­a­bet­ic ke­toaci­do­sis (DKA), a se­ri­ous and of­ten life-threat­en­ing con­se­quence of in­sulin in­suf­fi­cien­cy,” the agency said in a rare ex­pla­na­tion of its com­plete re­sponse let­ter. “Time-to-event analy­ses of the clin­i­cal tri­al da­ta showed ear­li­er de­vel­op­ment of DKA in so­tagliflozin-treat­ed pa­tients than in pa­tients as­signed to place­bo, with­out ev­i­dence that the risk stopped in­creas­ing over time.”

Un­like some of its larg­er peers that rarely chal­lenge the FDA once mul­ti­ple av­enues to over­turn the CRL have been de­nied, Lex­i­con re­mained de­ter­mined, ap­peal­ing the de­nial twice, and seek­ing a hear­ing in No­vem­ber 2021 to fur­ther dis­cuss the ap­pli­ca­tion with out­side ex­perts.

The com­pa­ny claims that so­tagliflozin is sim­i­lar to oth­er SGLT2 in­hibitors that are al­ready mar­ket­ed, like Janssen’s In­vokana and As­traZeneca’s Farx­i­ga, adding:

CDER may not dis­miss prece­dent by claim­ing that each case is dif­fer­ent; these ex­am­ples present a fac­tu­al ques­tion re­gard­ing the ex­tent of the ben­e­fits un­der­ly­ing the ben­e­fit-risk as­sess­ment, and ul­ti­mate­ly, the ap­proval of so­tagliflozin. Treat­ing sim­i­lar­ly sit­u­at­ed prod­ucts dif­fer­ent­ly, with­out ad­e­quate and rea­soned ex­pla­na­tion, is ar­bi­trary and capri­cious in vi­o­la­tion of the APA.

The clin­i­cal pro­gram for so­tagliflozin, Lex­i­con con­tends, fea­tured three large, mul­ti­cen­ter, ran­dom­ized Phase III tri­als, all of which achieved their pre-spec­i­fied pri­ma­ry end­points and demon­strat­ed a sta­tis­ti­cal­ly sig­nif­i­cant and clin­i­cal­ly mean­ing­ful im­prove­ment in gly­co­sy­lat­ed he­mo­glo­bin (HbA1c) lev­els.

The com­pa­ny al­so says that the FDA’s con­cerns about the iden­ti­fied risk of DKA “can be ad­e­quate­ly mit­i­gat­ed by risk mit­i­ga­tion tools that CDER has used to mit­i­gate sim­i­lar risks in oth­er di­a­betes prod­ucts. DKA is not an in­signif­i­cant risk; how­ev­er, it is a risk that is en­dem­ic to T1DM and not unique to so­tagliflozin.”

Mov­ing for­ward, ac­cord­ing to an agree­ment made be­tween the FDA and Lex­i­con in Sep­tem­ber, if CDER con­tin­ues to rec­om­mend that the FDA’s Of­fice of the Com­mis­sion­er de­ny Lex­i­con’s re­quest for a hear­ing, CDER shall sub­mit Lex­i­con’s re­quest for a hear­ing, Lex­i­con’s re­sponse, CDER’s analy­sis of Lex­i­con’s re­quest for a hear­ing in­clud­ing any ad­di­tion­al analy­sis by CDER of Lex­i­con’s re­sponse, and a pro­posed or­der deny­ing the re­quest for a hear­ing to the Of­fice of the Com­mis­sion­er by Jan. 31, 2023.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.

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 re­ports ini­tial 'no sig­nal' for stroke risk with Pfiz­er boost­ers, launch­es con­comi­tant flu shot study

The FDA hasn’t detected any potential safety signals, including for stroke, in people aged 65 years and older who have received Pfizer’s bivalent Covid booster, one senior official told members of the agency’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Thursday.

The update comes as the FDA and CDC investigate a “preliminary signal” that may indicate an increased risk of ischemic stroke in older Americans who received Pfizer’s updated shot.

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.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.

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.