UP­DAT­ED: 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.

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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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Carole Ben-Maimon, CEO of Larimar Therapeutics

Lari­mar to re­spond to FDA this quar­ter on 15-month clin­i­cal hold of PhI Friedre­ich's atax­ia drug

More than a year after the FDA clamped down on Larimar Therapeutics with a clinical hold on its lead drug, the biotech thinks it has a way to get that lifted — and an answer could come next quarter if all goes to plan.

Amid a 15-month setback, the biotech plans on filing a complete response to the FDA’s concerns over its drug, CTI-1601, sometime this quarter, which is supposed to elicit an answer from the agency within 30 days, per the regulator.

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.