What's com­ing? Paz­dur, Marks and Wood­cock dis­cuss FDA changes

Three of the FDA’s di­rec­tors — Richard Paz­dur, Pe­ter Marks and Janet Wood­cock — took the stage Wednes­day at Pre­vi­sion Pol­i­cy’s Bio­phar­ma Con­gress to dis­cuss all things FDA: from why the agency is viewed more pos­i­tive­ly now than in the past to what needs to hap­pen in each of their cen­ters.

CDER di­rec­tor Wood­cock said that the dif­fer­ence be­tween years past, when FDA was viewed neg­a­tive­ly, and now is that there has been a sort of sci­en­tif­ic rev­o­lu­tion, with bi­ol­o­gy be­ing har­nessed in nov­el ways and in­vest­ments at NIH pay­ing off.

Richard Paz­dur

On­col­o­gy Cen­ter of Ex­cel­lence di­rec­tor Paz­dur al­so not­ed the tremen­dous growth in un­der­stand­ing dis­eases and in the im­munol­o­gy of can­cer.

“One part of the piece in on­col­o­gy is that our staff has em­braced these changes,” he said, not­ing they’re “not just bean coun­ters for sur­vival da­ta” but have got­ten in­volved in the sci­ence of on­col­o­gy. The staff are part­ners in the process rather than just tick­ing box­es, he said.

And Marks, di­rec­tor of the Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search, ex­plained how the idea of screen­ing li­braries of com­pounds has gone out the win­dow, while nowa­days it’s more about ra­tio­nal drug de­vel­op­ment – “and gene ther­a­py is the epit­o­me of that.”

On the top­ic of gene ther­a­py, Marks not­ed there are now 700 in­ves­ti­ga­tion­al new drug ap­pli­ca­tions be­fore FDA. But com­pare that with cell ther­a­pies, he said, not­ing a gray mar­ket of un­proven treat­ments, which in some cas­es are noth­ing bet­ter than bad­ly man­u­fac­tured snake-oil that don’t con­tain live cells. He al­so said the use of un­ap­proved stem cell ther­a­pies around the coun­try is a sur­ro­gate mark­er for how Right to Try may play out. FDA doesn’t usu­al­ly learn about what is go­ing on un­til some­thing re­al­ly bad hap­pens, Marks added.

On the prospects of what’s to come at FDA, Wood­cock not­ed the re­al-time re­view pi­lot in the On­col­o­gy Cen­ter of Ex­cel­lence, which re­views parts of a sub­mis­sion be­fore the en­tire ap­pli­ca­tion is sub­mit­ted, is “fore­shad­ow­ing some­thing big­ger.” But she al­so ex­plained how the speed of re­views does not re­al­ly in­flu­ence the re­sults, say­ing: “what has changed is the cost of these drugs, and it’s changed the de­bate be­cause of val­ue.”

Nowa­days and mov­ing in­to the fu­ture, there’s a so­ci­etal ben­e­fit and harm dis­cus­sion that im­plic­it­ly in­vokes “trade-offs in val­ue – that’s the new de­bate we’re hav­ing – too fast and too slow is re­al­ly not the is­sue.”

For Marks, the biggest prob­lem mov­ing for­ward for gene ther­a­pies is the quan­tum leap need­ed in man­u­fac­tur­ing and to ap­ply­ing the tech­niques be­yond just rare dis­eases. “We need to do the kind of trans­for­ma­tion Steve Jobs did for dig­i­tal,” with man­u­fac­tur­ing gene ther­a­pies. He al­so not­ed FDA is “very le­nient” about some of its man­u­fac­tur­ing stan­dards for get­ting gene ther­a­pies in­to Phase 1 tri­als, but scal­ing up the man­u­fac­tur­ing is what’s dif­fi­cult.

Mov­ing in­to the fu­ture leg­isla­tive­ly, Wood­cock said she’s in­ter­est­ed in leg­is­la­tion on gener­ic drug la­bel­ing. “We have to clean up the ar­ma­men­tar­i­um so it doesn’t get out of date,” she said. She fur­ther not­ed FDA is work­ing with Con­gress on over-the-counter  drug re­forms, which is the ba­sis for the Of­fice of New Drug mod­ern­iza­tion. “If we don’t get the OTC re­form, we’ll have to pull back on the OND re­forms,” she said.


Im­age: Janet Wood­cock

First pub­lished here. reg­u­la­to­ry fo­cus is the flag­ship on­line pub­li­ca­tion of the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety (RAPS), the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care and re­lat­ed prod­ucts, in­clud­ing med­ical de­vices, phar­ma­ceu­ti­cals, bi­o­log­ics and nu­tri­tion­al prod­ucts. Email news@raps.org for more in­for­ma­tion.

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.

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.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

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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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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.

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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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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In­cyte’s PD-(L)1 in­hibitor head­ed for an ODAC show­down next month

The FDA’s Oncologic Drugs Advisory Committee will spend a half day on June 24 reviewing Incyte’s PD-(L)1 inhibitor retifanlimab as a treatment for locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) for those who have progressed on or who are intolerant of platinum-based chemotherapy.

The eighth PD-(L)1 entrant in January nabbed a priority review and an orphan designation from the FDA, which sets the agency’s final decision date as July 25.