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.

And ad­comm mem­bers large­ly agreed with the agency to­day, 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.

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.

Even though many biopharma leaders have come together in recent years to address its gender gap, the consensus is clear: We still have a long way to go.

Companies this year were 2.5 times more likely than last year to have a diversity and inclusion program in place, according to a recent BIO survey, but women are still largely absent from executive roles. Getting women to enter the industry isn’t the problem — studies show that they represent just under half of all biotech employees around the world. But climbing through the ranks can be challenging, as women still report facing stereotypes, and, unfortunately, harassment.

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The FDA authorized AstraZeneca’s long-acting monoclonal antibody cocktail to prevent Covid-19 in patients who are immunocomprised, providing the first level of additional protection for people who may not be adequately protected by vaccines.

Although it will only be for a small subset of the population, the EUA marks another pandemic milestone. Many people with conditions or on treatments that severely weaken their immune systems, such as cancer or multiple sclerosis, have found themselves left behind as much of the the country reopened last year.

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Each year, we aim to highlight 20 extraordinary women who are leaving their mark on drug R&D — and this year’s group was no exception.

Our list, while by no means exhaustive, includes scientists, CEOs, researchers and professors who are supercharging the discovery and development of new therapies worldwide. Our team of writers spent time with each honoree (with a few exceptions), learning their stories and sketching profiles, which you’ll find in our special report.

For the second time, we brought the celebration to a live virtual audience, featuring an award presentation followed by a panel on what it takes to break the glass ceiling in biopharma with Kojin Therapeutics CEO Luba Greenwood, AskBio CEO Sheila Mikhail, and Silverback Therapeutics CEO Laura Shawver. Our panelists had a lively discussion on how the industry’s culture has changed, how to handle sexual harassment, the progress we’ve made and the challenges that still hold women back today.

We applaud each of our honorees for scaling the heights of biopharma R&D. You got to meet most of them via brief recordings we played during our live event. Below, you’ll find bonus videos offering a longer glimpse into those interviews. And if you didn’t get a chance to tune in to our main event live, you can replay the entire show.

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KEY POINTS

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Please signup to continue — it’s fast and free. This article is sponsored by Catalent and produced by Endpoints Studio. Members of the public disembark a train at King Cross Station in London, on the day that extra measures are put in place to fight the spread of the Omicron variant of Covid-19. Since Nov. 30, it’s been mandatory for people in England to wear face coverings in shops and on public transport. (Ben Cawthra/Sipa USA/Sipa via AP Images)

Like hundreds of other virologists and epidemiologists, Benjamin tenOever’s Thanksgiving weekend was interrupted with emails about an emergency Omicron meeting.

But when he logged onto a WHO conference call 9 a.m. Monday morning, officials had a surprisingly upbeat spin on the little-understood variant that had already prompted leaders around the world, fearful the strain could evade vaccines, to close their borders to broad swaths of Southern Africa.

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President Biden’s nominee to be the next FDA commissioner officially has his Senate confirmation hearing set for next Tuesday. Rob Califf, who’s prepping for his second run as FDA commish, will be peppered with questions by senators ahead of an up or down vote that will likely go Califf’s way.

At least four Democrats, including Bernie Sanders and West Virginia’s Joe Manchin, have already said they won’t vote for Califf, as they did during Califf’s first confirmation (89-4 was the final vote on that one). While Califf’s industry ties and views on the pandemic will likely be the focus of the hearing, all eyes will be on the Republicans (given the tight R-D split in the Senate), and whether they’re willing to back a Biden nominee.

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Stephen Hahn (AP Photo/Alex Brandon, File)

Since leaving the FDA’s top post last January, Steve Hahn has been busy, jumping between multiple industry positions thanks to Flagship Pioneering, and most recently taking the helm at a startup focused on the detection of early cancer with a simple blood test.

Hahn’s new company, known as Harbinger Health, will receive $50 million from Flagship to use a proprietary platform combining AI and machine learning to potentially create an entirely new paradigm for cancer diagnosis, enabling early therapeutic interventions or prevention. Hahn’s prior work as chief medical executive of the University of Texas MD Anderson Cancer Center will likely inform his new role, where he’s serving as a Flagship CEO-partner as well as CEO of Harbinger.

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Ugur Sahin, BioNTech CEO (Frank Rumpenhorst/dpa via AP Images)

The first substantial evidence for how mRNA vaccines will hold up against the new Omicron variant was released Tuesday night from scientists in South Africa.

The study, conducted by mixing sera from vaccinated individuals with live Omicron virus, showed that the variant could largely — but not entirely — dodge antibodies elicited by the Pfizer-BioNTech vaccine.

The result suggests that the vaccines will be less effective at preventing infection by Omicron. But because many antibodies do still bind to the virus, experts say, boosters should help stem the decline. And efficacy will likely hold up against the most important metric for vaccines: preventing severe disease.

Myelodysplastic syndrome is not only hard to say, it’s also hard to explain. So Novartis hired Noma Bar, an artist and illustrator well-known for his simple and striking imagery to create a video that explains the rare blood cancer.

The 2-minute video uses bold colors and seamless graphics that morph from image to image. A white blood cell, for instance, turns into a Pacman-like character gobbling infection, while a drop of blood turns into a dial pointer and then an exclamation point.

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