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.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

Endpoints Premium

Premium subscription required

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

FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

Endpoints Premium

Premium subscription required

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

CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.

Joshua Brumm, Dyne Therapeutics CEO

FDA or­ders DMD tri­al halt, rais­ing ques­tions about a whole class of promis­ing drugs

Dyne Therapeutics’ stock took a nasty hit this morning after the biotech put out word that the FDA had slapped a clinical hold on their top program for Duchenne muscular dystrophy. And now speculation is bouncing around Biotwitter that there could be a class effect at work here that would implicate other drug developers in the freeze.

Dyne execs didn’t have a whole lot to say about why the FDA sidelined their IND for DYNE-251 in DMD while “requesting additional clinical and non-clinical information for” the drug.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,200+ biopharma pros reading Endpoints daily — and it's free.

Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,200+ biopharma pros reading Endpoints daily — and it's free.

Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,200+ biopharma pros reading Endpoints daily — and it's free.

Michel Vounatsos, Biogen CEO (Credit: World Economic Forum/Ciaran McCrickard)

An un­ortho­dox pro­pos­al for Bio­gen's Medicare-man­dat­ed Aduhelm tri­al

Biogen has gone full blitz since Medicare announced it would only cover its new Alzheimer’s drug when used in clinical trials, accusing the agency of discriminating against Alzheimer’s patients and trying to get physicians to change regulators’ minds.  Critics, meanwhile, cheered what they see as a necessary wall protecting payers and patients from an unproven and unsafe drug.

Far less attention, though, has gone to what a Medicare-funded clinical trial would actually look like. Biogen has operated as if it would be a standard late-stage Alzheimer’s trial, enrolling a couple thousand patients and giving half placebo.

Endpoints Premium

Premium subscription required

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