Janet Woodcock, director of the Center for Drug Evaluation and Research (Tom Williams/CQ Roll Call via AP Images)

CDER's Janet Wood­cock: Phar­ma, reg­u­la­tors have lessons to learn from Covid-19

When phar­ma­ceu­ti­cal com­pa­nies, health care lead­ers and reg­u­la­tors fi­nal­ly get a chance to de­brief and pull lessons learned from the coro­n­avirus pan­dem­ic, a chief take­away may re­volve around the many missed re­search op­por­tu­ni­ties. How­ev­er, learn­ings from Covid-19 may one day lead to nov­el tri­al de­sign and in­creased co­op­er­a­tion among these play­ers promise a bet­ter path for­ward when speed and safe­ty need equal con­sid­er­a­tion. This mes­sage was among many shared by a lead­ing reg­u­la­tor in a 9 No­vem­ber au­dio in­ter­view with ed­i­tors at the New Eng­land Jour­nal of Med­i­cine (NE­JM).

Janet Wood­cock, the long­time di­rec­tor of the FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search, stepped away from that role to par­tic­i­pate in Op­er­a­tion Warp Speed (OWS), the gov­ern­ment’s coro­n­avirus treat­ment and ther­a­peu­tics ac­cel­er­a­tor. In con­ver­sa­tion with NE­JM’s ed­i­tor-in-chief, Er­ic Ru­bin, deputy ed­i­tor Lind­sey Baden, and ex­ec­u­tive man­ag­ing ed­i­tor Stephen Mor­ris­sey, Wood­cock shared her unique per­spec­tive as a reg­u­la­tor-turned-drug de­vel­op­er dur­ing the pan­dem­ic.

The prob­lem with an EUA

Though emer­gency use au­tho­riza­tions (EUAs) are ap­pro­pri­ate when a nov­el dis­ease like Covid-19 strikes – in the case when, said Wood­cock, “our hands are emp­ty” – the ear­ly de­ploy­ment of a ther­a­py or vac­cine in­to the com­mu­ni­ty means “that it can be dif­fi­cult to con­tin­ue to do the re­search you need to do,” she said.

Ide­al­ly, the de­ploy­ment of each EUA should have been a re­search op­por­tu­ni­ty: “They should have ran­dom­ized the first pa­tient…We’d be in a bet­ter sit­u­a­tion of un­der­stand­ing” more about which pop­u­la­tions ben­e­fit and what the true ef­fec­tive­ness is of the ther­a­pies au­tho­rized to date, she said. The RE­COV­ERY tri­al in the UK, an adap­tive, re­al-world ran­dom­ized tri­al that is yield­ing on­go­ing in­for­ma­tion about Covid-19 an­tivi­rals and ther­a­peu­tics, is an achiev­able ex­am­ple of how to col­lect high-qual­i­ty da­ta dur­ing clin­i­cal care.

When is there enough ev­i­dence gath­ered from these sources to war­rant the is­suance of an EUA? “To your ques­tion, this is a clas­sic dilem­ma for peo­ple with very se­ri­ous ill­ness, which is how much cer­tain­ty do you want to have, ver­sus the per­il of a mor­tal ill­ness,” not­ed Wood­cock.

What tri­als are oc­cur­ring world­wide are dis­ag­gre­gat­ed and small, not­ed Wood­cock, with the cur­rent es­ti­ma­tion of OWS be­ing that on­ly about 5% of ther­a­peu­tics tri­als will yield ev­i­dence high enough for pub­lish­able stud­ies. OWS has at­tempt­ed to over­come some of the het­ero­gene­ity and da­ta qual­i­ty is­sues by form­ing a “da­ta lake” for big da­ta analy­sis.

In reg­u­lar In­ter­na­tion­al Coali­tion of Med­i­cines Reg­u­la­to­ry Au­thor­i­ties (ICM­RA) calls in­volv­ing reg­u­la­tors for up to 50 coun­tries, Wood­cock said, “I’ve pre­sent­ed the da­ta on the world­wide tri­als and the lack of ac­tion­able tri­als, and I think every­one is on the same page about this and there will be an op­por­tu­ni­ty for … the med­ical ecosys­tem world­wide to come to­geth­er and say, ‘We can do bet­ter.’ We can have a more co­or­di­nat­ed and co­he­sive re­sponse.”

Go­ing for­ward, hope for co­op­er­a­tion and in­no­va­tion

Asked about the best way for stake­hold­ers to be well po­si­tioned in terms of in­fra­struc­ture and sci­en­tif­ic ap­proach the next time a rapid­ly spread­ing in­fec­tion chal­lenges the globe, Wood­cock point­ed to the promise of ad­just­ing clin­i­cal tri­al de­sign. “For a long time, I’ve been a pro­po­nent of mas­ter pro­to­cols and plat­form tri­als,” she said. “I think we need to have things like that set up and ready to go. They can cer­tain­ly build re­al­ly valu­able in­for­ma­tion about stan­dard of care dur­ing the pan­dem­ic,” she said. “And we al­so need some agree­ment amongst in­ves­ti­ga­tors.”

What’s more, though gov­ern­ment needs to take the lead in mov­ing tri­als along, it’s vi­tal that phar­ma­ceu­ti­cal com­pa­nies par­tic­i­pate as well. Aca­d­e­m­ic-led tri­als are ide­al in that they are freer from po­ten­tial con­flicts of in­ter­est, but aca­d­e­m­ic med­ical cen­ters lack in­fra­struc­ture to run large, well-de­signed tri­als at speed, said Wood­cock. When re­search­ing a com­mon ill­ness like Covid-19 dur­ing a pan­dem­ic, there is the ad­di­tion­al prob­lem that “many of these pa­tients are in the com­mu­ni­ty, so they don’t have an op­por­tu­ni­ty to par­tic­i­pate in tri­als,” she not­ed. The reach that phar­ma­ceu­ti­cal com­pa­nies can achieve with con­tract re­search or­ga­ni­za­tions can over­come some of these hur­dles.

“I think the prob­lem right now is aca­d­e­m­ic tri­als are felt to be slow and clunky,” and of­ten have da­ta col­lec­tion is­sues re­lat­ed to slow ac­cru­al and low num­bers. Speak­ing some­what tongue in cheek, Wood­cock said she’s adopt­ed a quote from epi­demi­ol­o­gist Mar­tin Landry and dubbed it “Landry’s Rule”: “The num­ber of pa­tients en­rolled is in­verse­ly pro­por­tion­al to the num­ber of pro­fes­sors.”

At OWS, said Wood­cock, “We are lever­ag­ing the aca­d­e­m­ic net­works, but we’re try­ing to bring in a tremen­dous amount of in­fra­struc­ture sup­port,” though even with all the sup­port OWS has af­ford­ed, there have still been prob­lems with slow site ac­ti­va­tion and en­roll­ment, she ac­knowl­edged.

Asked about her per­spec­tive now that she’s tak­en off her reg­u­la­tor hat and is see­ing phar­ma­ceu­ti­cal de­vel­op­ment from the oth­er side of the fence, Wood­cock said, “I al­so ap­pre­ci­ate from this side the pres­sure the com­pa­nies are un­der to get things done, and get things out there, and how there’s con­stant pres­sure here that a lot of peo­ple don’t un­der­stand; they think we should just have these ther­a­pies out there.”

RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

Biogen CEO Michel Vounatsos (via Getty Images)

With ad­u­canum­ab caught on a cliff, Bio­gen’s Michel Vounatsos bets bil­lions on an­oth­er high-risk neu­ro play

With its FDA pitch on the Alzheimer’s drug aducanumab hanging perilously close to disaster, Biogen is rolling the dice on a $3.1 billion deal that brings in commercial rights to one of the other spotlight neuro drugs in late-stage development — after it already failed its first Phase III.

The big biotech has turned to Sage Therapeutics for its latest deal, close to a year after the crushing failure of Sage-217, now dubbed zuranolone, in the MOUNTAIN study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.

Pascal Soriot (AP Images)

As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.

Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

Af­ter Ko­dak de­ba­cle, US lends $1.1B to a syn­thet­ic bi­ol­o­gy com­pa­ny and their big Covid-19, mR­NA plans

In mid-August, as Kodak’s $765 million government-backed push into drug manufacturing slowly fell apart in national headlines, Ginkgo Bioworks CEO Jason Kelly got a message from his company’s government liaison: HHS wanted to know if they, too, might want a loan.

The government’s decision to lend Kodak three quarters of a billion dollars raised eyebrows because Kodak had never made drugs before. But Ginkgo, while not a manufacturing company, had spent the last decade refining new ways to produce materials inside cells and building automated facilities across Boston.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.

The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

Endpoints Premium

Premium subscription required

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

John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

Al­ny­lam gets the green light from the FDA for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1. The news comes just 4 days after the European Commission took the lead in offering a green light.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.

Leonard Schleifer, Regeneron CEO (Andrew Harnik/AP)

Trail­ing Eli Lil­ly by 12 days, Re­gen­eron gets the FDA OK for their Covid-19 an­ti­body cock­tail

A month and a half after becoming the experimental treatment of choice for a newly diagnosed president, Regeneron’s antibody cocktail has received emergency use authorization from the FDA. It will be used to treat non-hospitalized Covid-19 patients who are at high-risk of progressing.

Although the Rgeneron drug is not the first antibody treatment authorized by the FDA, the news comes as a significant milestone for a company and a treatment scientists have watched closely since the outbreak began.

FDA hands Liq­uidia and Re­vance a CRL and de­fer­ral, re­spec­tive­ly, as Covid-19 cre­ates in­spec­tion chal­lenge

Two biotechs said they got turned away by the FDA on Wednesday, in part due to pandemic-related travel restrictions.

North Carolina-based Liquidia Technologies was handed a CRL for its lead pulmonary arterial hypertension drug, citing the need for more CMC data and on-site pre-approval inspections, which the FDA hasn’t been able to conduct due to travel restrictions. The agency also deferred its decision on Revance Therapeutics’ BLA for its frown line treatment, because it needs to inspect the company’s northern California manufacturing facility. The action, Revance emphasized, was not a CRL.

In fi­nal days at Mer­ck, Roger Perl­mut­ter bets big on a lit­tle-known Covid-19 treat­ment

Roger Perlmutter is spending his last days at Merck, well, spending.

Two weeks after snapping up the antibody-drug conjugate biotech VelosBio for $2.75 billion, Merck announced today that it had purchased OncoImmune and its experimental Covid-19 drug for $425 million. The drug, known as CD24Fc, appeared to reduce the risk of respiratory failure or death in severe Covid-19 patients by 50% in a 203-person Phase III trial, OncoImmune said in September.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.

Covid-19 roundup: Eu­rope pur­chas­es 80M dos­es of Mod­er­na's vac­cine; CO­V­AXX se­cures $2.8B in emerg­ing mar­ket pre-or­ders

With the announcement of its vaccine efficacy data last week, Moderna is starting to line up customers for its Covid-19 mRNA jabs.

The Massachusetts-based biotech announced Wednesday it has agreed to sell an initial round of 80 million doses to the European Commission, with the option to double the amount to 160 million. Once the member states rubber stamp the approval, the deal will be finalized.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.