Clin­i­cal tri­al spon­sors have to dis­close decade’s worth of un­re­leased da­ta, fed­er­al judge rules

A decade’s worth of un­re­leased tri­al da­ta may soon see the light of day.

A New York fed­er­al judge ruled this week that the FDA and the NIH have for years mis­in­ter­pret­ed a law that would re­quire com­pa­nies, uni­ver­si­ties and oth­er clin­i­cal tri­al spon­sors to re­lease tri­al da­ta from stud­ies com­plet­ed be­tween 2007 and 2017. The rul­ing cov­ers drugs and med­ical de­vices that were ex­per­i­men­tal when the study was com­plet­ed but have since been ap­proved, po­ten­tial­ly putting hun­dreds of spon­sors out of com­pli­ance if they don’t put their re­sults on clin­i­cal­tri­

The FDA had been in­ter­pret­ing a ‘fi­nal rule’ added to 2007 law, known as the Food and Drug Ad­min­is­tra­tion Amend­ments Act, to mean that spon­sors on­ly had to re­port re­sults for tri­als that were com­plet­ed af­ter the law rule was pro­mul­gat­ed in 2017. Plain­tiffs said it was retroac­tive.

“The court has set aside that er­ro­neous in­ter­pre­ta­tion of the law and has said that the statute means what it has al­ways said,” Christo­pher Morten, the lawyer for the plain­tiffs, told End­points News. “So our hope here is that tri­al spon­sors are go­ing to start, fi­nal­ly, af­ter years of non­com­pli­ance, re­port­ing some of that miss­ing da­ta to the pa­tients.”

The FDA and the NIH did not put out state­ments fol­low­ing the rul­ing and did not im­me­di­ate­ly re­spond to re­quests for com­ment.

FDAAA was the law that re­quired spon­sors to reg­is­ter most tri­als on clin­i­cal­tri­, and in 2018 the change went in­to ef­fect re­quir­ing that com­pa­nies post re­sults with­in a year of the tri­al’s com­ple­tion. The gov­ern­ment in­ter­pret­ed it to mean on­ly the re­sults of tri­als com­plet­ed af­ter the law went in­to ef­fect.

The FDA and NIH’s ex­e­cu­tion of that rule, though, has been the sub­ject of ma­jor scruti­ny in the last few months. In­ves­ti­ga­tions in The Lancet and in Sci­ence pub­lished in Jan­u­ary found that tri­al spon­sors have wide­ly ig­nored the re­port­ing re­quire­ments since 2018. The Lancet study, by Ben Goldacre, found on­ly 41% of over 4,700 tri­als re­port­ed on time.  An­a­lyz­ing a sim­i­lar dataset, Sci­ence’s Charles Piller found 45% non­com­pli­ance and iso­lat­ed a group of 30 “ha­bit­u­al of­fend­ers” who col­lec­tive­ly failed to re­port the re­sults 67% of the time.

Ad­vo­cates for greater trans­paren­cy say this kind of ob­fus­ca­tion hurts the field by giv­ing doc­tors and re­searchers on­ly a par­tial glimpse at the over­all re­sults. It can even be dan­ger­ous, Morten ar­gued. He cit­ed Vioxx, the painkiller Mer­ck pulled off the mar­ket in 2004 af­ter stud­ies showed an in­creased risk of stroke. Had Mer­ck dis­closed pre-ap­proval tri­al re­sults soon­er, Morten said, the risk could have been caught soon­er.

The case was brought by for­mer as­so­ciate FDA com­mis­sion­er Pe­ter Lurie and NYU jour­nal­ist Charles Seife, who ar­gued a mis­in­ter­pre­ta­tion of the rule has im­ped­ed their work more broad­ly. The rul­ing takes the re­port­ing re­quire­ments pre­vi­ous­ly ap­plied on­ly to tri­als com­plet­ed since 2018 and ap­plies them to those com­plet­ed since 2007.

“That’s hurt pa­tients who lack the op­por­tu­ni­ty to learn about the drugs they take, it’s hurt doc­tors that lack in­for­ma­tion on the drugs they pre­scribe, and it’s hurt re­searchers like Charles and Pe­ter,” Morten said.

It’s not clear, though, how the rul­ing will be en­forced. The plain­tiffs were over­ruled on a sep­a­rate is­sue, in which they ar­gued the FDA and NIH were not abid­ing by a statute re­quir­ing them to give pub­lic no­tice of non­com­pli­ance to com­pa­nies not abid­ing by the FDAAA rules.

The gov­ern­ment could yet ap­peal the rul­ing but it’s not yet clear if they will.

Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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UP­DAT­ED: Bio­gen shares spike as ex­ecs com­plete a de­layed pitch for their con­tro­ver­sial Alzheimer's drug — the next move be­longs to the FDA

Biogen is stepping out onto the high wire today, reporting that the team working on the controversial Alzheimer’s drug aducanumab has now completed their submission to the FDA. And they want the agency to bless it with a priority review that would cut the agency’s decision-making time to a mere 6 months.

The news drove a 10% spike in Biogen’s stock $BIIB ahead of the bell.

Part of that spike can be attributed to a relief rally. Biogen execs rattled backers and a host of analysts earlier in the year when they unexpectedly delayed their filing to the third quarter. That delay provoked all manner of speculation after CEO Michel Vounatsos and R&D chief Al Sandrock failed to persuade influential observers that the pandemic and other factors had slowed the timeline for filing. Actually making the pitch at least satisfies skeptics that the FDA was not likely pushing back as Biogen was pushing in. From the start, Biogen execs claimed that they were doing everything in cooperation with the FDA, saying that regulators had signaled their interest in reviewing the submission.

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FDA bars the door — for now — against Mer­ck’s star can­cer drug af­ter Roche beat them to the punch

Merck has been handed a rare setback at the FDA.

After filing for the accelerated approval of a combination of their star PD-1 drug Keytruda with Eisai’s Lenvima as a first-line treatment for unresectable hepatocellular carcinoma, the FDA nixed the move, handing out a CRL because Roche beat them to the punch on the same indication by a matter of weeks.

According to Merck:

Ahead of the Prescription Drug User Fee Act action dates of Merck’s and Eisai’s applications, another combination therapy was approved based on a randomized, controlled trial that demonstrated overall survival. Consequently, the CRL stated that Merck’s and Eisai’s applications do not provide evidence that Keytruda in combination with Lenvima represents a meaningful advantage over available therapies for the treatment of unresectable or metastatic HCC with no prior systemic therapy for advanced disease. Since the applications for KEYNOTE-524/Study 116 no longer meet the criteria for accelerated approval, both companies plan to work with the FDA to take appropriate next steps, which include conducting a well-controlled clinical trial that demonstrates substantial evidence of effectiveness and the clinical benefit of the combination.

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Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

A new study points to $6.5B in pub­lic sup­port build­ing the sci­en­tif­ic foun­da­tion of Gilead­'s remde­sivir. Should that be re­flect­ed in the price?

By drug R&D standards, Gilead’s move to repurpose remdesivir for Covid-19 and grab an emergency use authorization was a remarkably easy, low-cost layup that required modest efficacy and a clean safety profile from just a small group of patients.

The drug OK also arrived after Gilead had paid much of the freight on getting it positioned to move fast.

In a study by Fred Ledley, director of the Center for Integration of Science and Industry at Bentley University in Waltham, MA, researchers concluded that the NIH had invested only $46.5 million in the research devoted to the drug ahead of the pandemic, a small sum compared to the more than $1 billion Gilead expected to spend getting it out this year, all on top of what it had already cost in R&D expenses.

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Roger Tung, Concert Pharmaceuticals CEO (Concert)

Con­cert gets BTD for alope­cia drug, set­ting up a late-stage show­down with gi­ant ri­val Pfiz­er

Concert Pharmaceuticals’ path to developing a drug that treats alopecia areata has been bumpy, but the pharma company scored a win Wednesday.

The FDA granted Concert a Breakthrough Therapy Designation (BTD) for its oral Janus kinase inhibitor, named CTP-543, paving the way for a Phase III study of the drug to begin in the fourth quarter of 2020. The news follows positive Phase II results from last September, which saw the drug meet its primary endpoint in both 8 mg and 12 mg twice-daily doses.

Covid-19 roundup: Mod­er­na sticks to Ju­ly for its Phase III as ru­mors swirl; Fol­low­ing US lead, EU buys up Covid-19 treat­ments

The Phase III might be delayed from its original early July goal, but Moderna says it will still kick off the pivotal study for what could ultimately be the first Covid-19 vaccine before the end of the month.

A day after Reuters reported that squabbling between the Cambridge biotech and government regulators had held up the trial by about two weeks, Moderna released a statement saying that they had completed enrollment of their 650-person Phase II trial and were on track to begin Phase III by the end of the month. The protocol for that study, which is meant to prove whether or not the vaccine can prevent people from becoming sick, has been finalized, they said.

Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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Stephen Hahn, AP

Trump and Navar­ro press again for hy­drox­y­chloro­quine. Can the FDA stay in­de­pen­dent?

Tuesday morning, economist and Trump advisor Peter Navarro walked onto the White House driveway and promptly brought a political cloud back onto the FDA.

Speaking to a White House pool reporter, Navarro said that four Detroit doctors were, based on a single disputed study, filing for the FDA to again issue an emergency authorization for hydroxychloroquine, the anti-malarial pill that President Trump hyped for months as a Covid-19 treatment over the objections of his own scientists. Then, while avoiding directly calling for the FDA to OK the drug, blasted the agency. He said its decision to pull an earlier authorization “was based on bad science” and “had a tremendously negative effect” on doctors and patients.

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Noubar Afeyan, Flagship CEO and Tessera chairman (Victor Boyko/Getty Images)

Flag­ship ex­ecs take a les­son from na­ture to mas­ter ‘gene writ­ing,’ launch­ing a star-stud­ded biotech with big am­bi­tions to cure dis­ease

Flagship Pioneering has opened up its deep pockets to fund a biotech upstart out to revolutionize the whole gene therapy/gene editing field — before gene editing has even made it to the market. And they’ve surrounded themselves with some marquee scientists and execs who have crowded around to help shepherd the technology ahead.

The lead player here is Flagship general partner Geoff von Maltzahn, an MIT-trained synthetic biologist who set out in 2018 to do CRISPR — a widely used gene editing tool — and other rival technologies one or two better. Von Maltzahn has been working with Sana co-founder Jake Rubens, another synthetic biology player out of MIT who he describes as his “superstar,” who’s taken the CSO role.

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