FDA rushed to ap­prove new drugs in 2019, some­times way ahead of sched­ule. Could that be dan­ger­ous?

While the ros­ter of 48 drugs (plus 4 no­table bi­o­log­ics) the FDA ap­proved in 2019 didn’t break any records with the sheer num­ber it was re­mark­able in one as­pect: The agency reached deep in­to a group of ther­a­pies they didn’t need to make a de­ci­sion on un­til lat­er this year, in some cas­es speed­ing drugs up by months ahead of even pri­or­i­ty re­view dead­lines.

On the sur­face, that’s great news for drug­mak­ers and the pa­tients they hope to help. But ac­cord­ing to a re­cent study on rushed ap­provals, it could al­so spell safe­ty trou­bles down the road.

Lau­ren Co­hen

Back in Ju­ly, a trio of econ­o­mists at NBER crunched the da­ta on drugs OK’d be­fore sup­posed dead­lines such as the end of months, years or be­fore hol­i­days and found that treat­ments ap­proved un­der these ap­par­ent “desk-clear­ing” ef­forts — in which reg­u­la­tors felt the pres­sure of in­for­mal per­for­mance bench­marks — are more like­ly to be as­so­ci­at­ed with post­mar­ket safe­ty is­sues.

“We see about twice as many ad­verse ef­fects,” Lau­ren Co­hen, a pro­fes­sor of fi­nance and en­tre­pre­neur­ial man­age­ment at Har­vard Busi­ness School and one of the au­thors, told the Wall Street Jour­nal.

Co­hen and his col­leagues, Umit Gu­run of the Uni­ver­si­ty of Texas at Dal­las and Danielle Li of MIT, con­sid­ered on­ly the surge of ap­provals in De­cem­ber, at the end of each month and be­fore hol­i­days such as Thanks­giv­ing.

In 2019 sev­en out of 48 nov­el chem­i­cal en­ti­ties were ap­proved in De­cem­ber, large­ly in line with the 15% pro­por­tion that the re­searchers not­ed in pre­vi­ous years. But no­tably, 21 OKs came through in Q4, ac­count­ing for 43% of the whole crop.

FDA spokesper­son Nathan Arnold ac­knowl­edged the De­cem­ber jump pat­tern but told the Jour­nal that its share has ac­tu­al­ly di­min­ished from the 1980s.

“While we can­not speak di­rect­ly to the re­sults on in­for­mal dead­lines high­light­ed in this study, FDA has—on mul­ti­ple oc­ca­sions—in­ves­ti­gat­ed a close­ly re­lat­ed is­sue, which is the re­la­tion­ship be­tween for­mal PDU­FA dead­lines and post­mar­ket safe­ty of drugs,” Arnold added. “We have not found ev­i­dence of such a re­la­tion­ship.”

Drugs that ap­peared to have been ap­proved with lit­tle heed of the PDU­FA dead­lines might be an­oth­er is­sue. Ver­tex’s Trikaf­ta (for cys­tic fi­bro­sis), BeiGene’s Brukin­sa (for man­tle cell lym­phoma), No­var­tis’ Adakveo and Glob­al Blood Ther­a­peu­tics’ Oxbry­ta (for sick­le cell dis­ease), as well as Al­ny­lam’s Givlaari (for acute he­pat­ic por­phyr­ia ) and As­traZeneca/Dai­ichi Sankyo’s En­her­tu (for HER+ breast can­cer) all be­longed to that group.

Co­hen, Gu­run and Li pre­scribed a so­lu­tion for the safe­ty con­cerns they spot­ted:

A po­ten­tial pol­i­cy re­sponse to the pat­terns we doc­u­ment is to more care­ful­ly scru­ti­nize drugs that are ap­proved dur­ing such out­put surges. Reg­u­la­tors could, for in­stance, re­view end-of-year de­ci­sions in the fol­low­ing year be­fore pro­vid­ing an ul­ti­mate ap­proval (or lack there­of).

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; 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 still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.

Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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UP­DAT­ED: In­ter­nal Trump-era emails re­veal a pletho­ra of celebs, com­pa­nies vy­ing for FDA’s at­ten­tion

The FDA on Thursday publicly released a trove of about 500 pages of internal and heavily redacted emails, showing how celebrities like Dr. Oz and Laura Ingraham vied for the FDA’s attention on Covid-related issues that ultimately proved to be a waste of time.

Many of the conversations, obtained via the Freedom of Information Act, involve major Trump-era health officials who, in retrospect, made crucial and often ill-advised decisions on increasing access to the over-hyped hydroxychloroquine.

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