FDA ad­comm votes unan­i­mous­ly against Reata's po­ten­tial Al­port syn­drome treat­ment

The US FDA’s Car­dio­vas­cu­lar and Re­nal Drugs Ad­vi­so­ry Com­mit­tee on Wednes­day vot­ed 13-0 that the agency should not ap­prove Rea­ta Phar­ma­ceu­ti­cals’ bar­dox­olone methyl cap­sules as a treat­ment to slow the pro­gres­sion of chron­ic kid­ney dis­ease in those with the rare Al­port syn­drome.

The lop­sided vote fol­lows sim­i­lar com­ments from FDA on Mon­day, which paint­ed an over­whelm­ing­ly neg­a­tive opin­ion on Rea­ta’s $RE­TA po­ten­tial drug, ac­cord­ing to brief­ing doc­u­ments re­leased ahead of to­day’s meet­ing.

Rea­ta’s stock price fell by an­oth­er 44% in af­ter-hours trad­ing, af­ter a pre­vi­ous 30+% drop ear­li­er in the week.

And ad­comm mem­bers large­ly agreed with the agency Wednes­day, say­ing safe­ty con­cerns gave them se­ri­ous pause, while tak­ing is­sue with the way Rea­ta ran its Phase III tri­al, and the com­plex­i­ty of the da­ta pre­sent­ed. Mem­bers of the com­mit­tee al­so sought clar­i­fi­ca­tions on why Rea­ta used eGFR as the main mea­sure for its Phase III, not­ing oth­er mea­sures might have been more in­for­ma­tive.

“FDA set the tone and the com­mit­tee re­sound­ing­ly agreed, dis­count­ing all of Rea­ta’s ar­gu­ments and leav­ing al­most ze­ro chance of ap­proval,” Baird biotech an­a­lyst Bri­an Sko­r­ney wrote in a note to in­vestors.

The use of eGFR, which is an es­ti­mate of the kid­ney’s fil­tra­tion rate, was meant to as­sess dis­ease pro­gres­sion, with Rea­ta ar­gu­ing that its Phase III showed pa­tients treat­ed with bar­dox­olone ex­pe­ri­enced a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in kid­ney func­tion as mea­sured by eGFR at Week 100 and Week 104, com­pared to pa­tients treat­ed with place­bo.

Near­ly every ad­comm mem­ber seemed to dis­agree with that con­clu­sion.

Pan­elist Paul Palevsky, chief of the kid­ney med­i­cine sec­tion at the VA Pitts­burgh Health­care Sys­tem, said that as much as he wants to see a drug that has an al­ter­na­tive mech­a­nism for im­prov­ing func­tion for this rel­a­tive­ly rare form of kid­ney dis­ease, he’s “quite con­cerned that the da­ta pro­vid­ed does not meet the bar of show­ing this will slow the time to end stage kid­ney dis­ease.”

Ad­comm mem­ber Patrick Nach­man, pro­fes­sor of med­i­cine at the Uni­ver­si­ty of Min­neso­ta, al­so ex­pressed wor­ries about the gen­er­al­iz­abil­i­ty of the da­ta pre­sent­ed, say­ing that the da­ta did not show ben­e­fit, but that he’s sen­si­tive to the idea there might be a group of pa­tients that could ben­e­fit from this treat­ment.

In the sum­ma­ry af­ter the first dis­cus­sion ques­tion of the meet­ing, chair of the ad­comm Ju­lia Lewis, pro­fes­sor of med­i­cine at Van­der­bilt, raised sev­er­al lin­ger­ing ques­tions too, like why on­ly en­roll 11 ado­les­cents in the Phase III if the spon­sor is seek­ing an in­di­ca­tion for an age group of 12 and up?

Pan­elist Su­san Mend­ley of the NIH’s Na­tion­al In­sti­tute of Di­a­betes and Di­ges­tive and Kid­ney Dis­eases al­so called on Rea­ta to study the drug more in the younger pop­u­la­tion as she’s con­cerned on the ef­fects of weight gain and growth out­weigh­ing the ben­e­fits.

Ad­comm mem­ber Gre­go­ry Gor­man, cap­tain in the med­ical corps of the US Navy, said that as a pe­di­atric nephrol­o­gist, he would’ve liked to hear that some pa­tient-re­port­ed out­come mea­sures were im­prov­ing. Oth­ers ques­tioned why the pa­tients were un­blind­ed to their GFR es­ti­mates, and how that could have bi­ased how they per­ceived their out­comes.

“I might have giv­en it the ben­e­fit of the doubt,” Gor­man said, but that’s nul­li­fied by bar­dox­olone’s safe­ty con­cerns, and even with the sta­tis­ti­cal­ly sig­nif­i­cant, small ef­fect, it might be nul­li­fied over the long term.

Orig­i­nal­ly de­vel­oped as a can­cer drug, bar­dox­olone was lat­er scut­tled by Rea­ta al­most a decade ago as a chron­ic kid­ney dis­ease drug due to deaths in a Phase III tri­al.

Rea­ta went back and ran the Phase III tri­al, which wrapped up four years ago, and on which this ap­pli­ca­tion is based.

Ed­i­tor’s note: Ar­ti­cle up­dat­ed with stock price re­ac­tion and com­ments from Baird’s Sko­r­ney.

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.

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.

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 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.

No­var­tis' ap­proved sick­le cell dis­ease drug fails to beat place­bo in PhI­II

Novartis’ sickle cell drug, approved in 2019 and branded as Adakveo, has failed an ongoing Phase III, according to preliminary results.

The Swiss pharma giant unveiled early data from the ongoing STAND Phase III study on Friday, saying that crizanlizumab showed no statistically significant difference between the drug at two different dose levels compared to placebo in annualized rates of vaso-occlusive crises that lead to a healthcare visit over the first year since being randomized into the trial.

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.

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.

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.