FDA puts its foot down on Mak­e­na: New meta-analy­sis does not change call to pull the drug

A re­cent­ly pub­lished meta-analy­sis of 31 ran­dom­ized, con­trolled tri­als on the pre­ma­ture birth drug Mak­e­na is not chang­ing the FDA’s pre­vi­ous de­ci­sion to pull its ac­cel­er­at­ed ap­proval and re­move it from the mar­ket, the agency said late last week.

The FDA’s de­ci­sion to pub­licly cri­tique the meta-analy­sis is the lat­est twist in a saga that most re­cent­ly in­volved the FDA propos­ing to with­draw the ac­cel­er­at­ed ap­proval of Mak­e­na, al­most a decade since it first won ap­proval, af­ter a large, ran­dom­ized con­fir­ma­to­ry tri­al failed to show the drug’s ben­e­fit for new­borns or its abil­i­ty to re­duce the risk of pre-term birth.

In dis­cussing the meta-analy­sis, the agency took is­sue with how it grouped dif­fer­ent tri­als to­geth­er, and how on­ly five of the 31 tri­als eval­u­at­ed Mak­e­na in the in­di­cat­ed pop­u­la­tion and com­pared it with place­bo.

“The EPP­PIC meta-analy­sis grouped to­geth­er HPC [hy­drox­yprog­es­terone caproate] tri­als of pa­tients with dif­fer­ences in their risk pro­files, in­clud­ing com­bin­ing women with a pri­or PTB [pre-term birth] and those with­out a pri­or PTB, and women with and with­out a short cervix. Be­cause of this group­ing, the meta-analy­sis does not pro­vide rel­e­vant in­for­ma­tion re­gard­ing Mak­e­na’s ef­fec­tive­ness for its ap­proved use,” the agency said Fri­day.

The FDA al­so said that it nev­er would have ap­proved Mak­e­na in the first place had it known what was in the da­ta from the con­fir­ma­to­ry tri­al.

De­spite the clar­i­ty from the agency, one of the com­pa­nies that makes Mak­e­na is not back­ing down.

Co­vis Phar­ma, which last No­vem­ber bought AM­AG Phar­ma­ceu­ti­cals, the ap­pli­ca­tion hold­er of Mak­e­na, said the find­ings of the meta-analy­sis reaf­firm the ef­fi­ca­cy of the drug.

Co­vis pre­vi­ous­ly re­quest­ed a hear­ing with the FDA (the agency hasn’t de­cid­ed yet whether to hold a hear­ing) to dis­cuss the sit­u­a­tion. Co­vis CEO Michael Porter said in a state­ment that the firm is “seek­ing the op­por­tu­ni­ty to dis­cuss da­ta-dri­ven next steps, in­clud­ing fur­ther eval­u­at­ing re­al-world da­ta.”

AM­AG re­port­ed more than $40 mil­lion in Mak­e­na rev­enue over the first two quar­ters of last year.

The FDA not­ed that Mak­e­na and its ap­proved gener­ic ver­sions will con­tin­ue to re­main on the mar­ket un­til the man­u­fac­tur­ers de­cide to re­move the drugs or the FDA com­mis­sion­er man­dates their re­moval.

Un­pack­ing the Aduhelm de­ci­sion, Ver­tex's half full glass, a $525M J&J breakup, and more

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By now you have surely read about the FDA’s controversial approval of Biogen’s Alzheimer’s drug and all its reverberations. But I’d still recommend checking out the meaty recap below to make sure you didn’t miss all the angles that the Endpoints team has covered. If you’d rather look ahead, look no further than our three-day virtual panels next week at BIO, where we will discuss what the new normal means for every part of the industry.

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What does a clear ma­jor­i­ty of the bio­phar­ma in­dus­try think of the FDA ap­proval of ad­u­canum­ab? 'Hor­ri­fy­ing' 'Dan­ger­ous' 'Con­fus­ing' 'Dis­as­ter'

Over the years, we’ve become used to seeing a consensus emerge early in our industry polls at Endpoints News. And when we took the pulse of drug hunters on the heels of a controversial FDA approval for aducanumab this week, it became immediately apparent that the vast majority of our readers — heavily concentrated among biopharma staffers and execs — were incensed by what they had just witnessed.

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David Knopman (Mayo Clinic via YouTube)

A sec­ond ad­comm mem­ber aban­dons his post in af­ter­math of con­tro­ver­sial ad­u­canum­ab de­ci­sion

As the fallout from the FDA’s approval of Alzheimer’s med aducanumab grows, a second member of the adcomm overseeing that drug’s review has walked away. But even with two experts now having resigned from that committee in protest, is there enough broad-level outrage to prevent another aducanumab from getting approved?

The FDA on Wednesday lost another member of its Peripheral and Central Nervous System Drugs Advisory Committee as Mayo Clinic neurologist David Knopman hit the exit over the agency’s decision to approve Biogen’s Alzheimer’s drug Aduhelm despite the committee’s near-unanimous vote against it.

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Aaron Kesselheim (Scott Eisen/AP Images for AIDS Healthcare Foundation)

Har­vard’s Aaron Kessel­heim re­signs from ex­pert pan­el in wake of ad­u­canum­ab OK, blast­ing FDA for ‘worst drug ap­proval de­ci­sion in re­cent U.S. his­to­ry'

A third member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee has resigned in the wake of Biogen’s controversial Aduhelm approval, slamming the agency as he left and further deepening the controversy surrounding the decision.

Harvard University professor Aaron Kesselheim quit in protest Thursday afternoon, calling the Aduhelm OK “probably the worst drug approval decision in recent U.S. history.” Kesselheim follows both Joel Perlmutter, a neurologist from Washington University in St. Louis, and David Knopman, a neurologist from the Mayo Clinic, out the door.

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FDA au­tho­rizes about 10M J&J vac­cine dos­es, trash­es 60M more from trou­bled Emer­gent plant

The FDA on Friday released about 10 million doses of J&J’s vaccine for use, and disposed of another 60 million doses that were manufactured at the now-shuttered Emergent BioSolutions facility in Baltimore where cross-contamination occurred.

The agency said it’s not yet ready to allow the Emergent plant to be included in the J&J EUA, but that may occur soon. FDA came to the decision to authorize some of the doses after reviewing facility records and quality testing results.

Janet Woodcock, acting FDA commissioner, at Thursday's Senate Appropriations hearing (Bill Clark/CQ Roll Call via AP Images)

Sen­a­tors lam­bast new Alzheimer’s drug’s price but give Janet Wood­cock a free pass on the ap­proval de­ci­sion

Senate Finance Democrats took aim at Biogen’s pricey new Alzheimer’s drug on Thursday, but members on both sides of the aisle at a separate appropriations hearing didn’t question acting FDA commissioner Janet Woodcock on the approval.

“I was appalled that Biogen priced their Alzheimer’s drug approved by the FDA at $56,000 per year — I’m not going to debate whether this is effective or not, but it’s double the household median income for Michiganders over the age of 65,” Sen. Debbie Stabenow (D-MI) said at the finance hearing.

FDA plans new stud­ies on ac­cel­er­at­ed ap­proval dis­clo­sures in bio­phar­ma ads

When people read biopharma companies’ websites about new drugs approved via the FDA’s accelerated pathway, like Biogen’s new Alzheimer’s drug, do they understand that these drugs may only be reasonably likely to predict clinical benefit and still require confirmatory studies?

That’s what the FDA’s Office of Prescription Drug Promotion wants to firm up as an agency analysis of direct-to-consumer websites for accelerated approval drugs previously found that only 21% of the disclosures used language directly from the label.

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Paul Hudson, Sanofi CEO (Eric Piermont/AFP via Getty Images)

Months af­ter FDA re­jec­tion, Sanofi touts piv­otal win for rare dis­ease drug su­tim­limab as it preps to re­file

One of the pillar drugs of Sanofi’s $11.6 billion pickup of Bioverativ hit a big setback late last year when the FDA sent its application for approval back. Now, as Sanofi gears up to resubmit the drug for review, the drugmaker is touting pivotal data it hopes will help take it over the finish line.

Sanofi’s sutimlimab nailed all three of its primary endpoints in its Phase III CADENZA study for patients with cold agglutinin disease, a rare disorder that can cause severe anemia, without a recent history of blood transfusion, the French drugmaker said Friday. The topline results will be presented at this weekend’s virtual EHA meeting.

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An ex­pen­sive watch, shell com­pa­nies and fake in­voic­es: How two Is­raeli traders tapped in­to a $100M glob­al biotech in­sid­er trad­ing ring

It appears that we have reached the end of the saga about the global insider trading ring that collectively reaped $100 million from placing “timely, profitable” trades in biotech stocks like Ariad, Pharmacyclics and Receptos.

Tomer Feingold and Dov Malnik — Israeli traders living in Switzerland — were the last out of eight to be charged as the SEC unraveled the scheme, which ran from 2013 through 2017. Together, according to a statement in March, the pair had pocketed more than $4 million.