Doug Throckmorton speaks via video conference to the Senate Finance Committee, June 2, 2020 (Andrew Caballero-Reynolds, AP Images)

FDA de­fends its over­sight of for­eign drugs amid Sen­ate, GAO crit­i­cism

Dur­ing a Sen­ate Com­mit­tee on Fi­nance hear­ing Tues­day, of­fi­cials from the FDA re­spond­ed to crit­i­cism from sen­a­tors and a new re­port from the Gov­ern­ment Ac­count­abil­i­ty Of­fice (GAO) on its over­sight of for­eign drug man­u­fac­tur­ers.

The hear­ing fol­lows FDA’s move to halt most for­eign in­spec­tions in March as a re­sult of the coro­n­avirus dis­ease (COVID-19) pan­dem­ic.

Much of the crit­i­cism cen­tered on the agency’s prac­tice of giv­ing for­eign fa­cil­i­ties ad­vanced no­tice of in­spec­tions while most do­mes­tic sur­veil­lance in­spec­tions are unan­nounced, as well as US re­liance on for­eign drug man­u­fac­tur­ing.

Open­ing the hear­ing, Chair­man Chuck Grass­ley (R-IA) point­ed out that most man­u­fac­tur­ing sites for fin­ished drugs and ac­tive phar­ma­ceu­ti­cal in­gre­di­ents (API) are lo­cat­ed out­side the US. Oth­er sen­a­tors raised con­cerns about the se­cu­ri­ty of the US phar­ma­ceu­ti­cal sup­ply chain, in­clud­ing Sens. John Cornyn (R-TX) and Mark Warn­er (D-VA).

Doug Throck­mor­ton, deputy di­rec­tor for reg­u­la­to­ry pro­grams at FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search, told sen­a­tors that FDA is look­ing for ways to lever­age ad­vanced man­u­fac­tur­ing to both im­prove drug qual­i­ty and pro­mote the on­shoring of drug man­u­fac­tur­ing.

“CDER’s vi­sion is to spur the in­dus­try to mod­ern­ize so that qual­i­ty can be con­sis­tent­ly and re­li­ably built in­to each tablet and vial they pro­duce,” he said.

How­ev­er, Throck­mor­ton al­so ac­knowl­edged that FDA lacks some of the in­for­ma­tion to have a thor­ough un­der­stand­ing of the ear­li­er stages of the phar­ma­ceu­ti­cal sup­ply chain, such as the sources of chem­i­cals used to pro­duce API and the API them­selves.

“We know sub­stan­tial­ly less about the sources of those prod­ucts than we do about API and … we know less about API and its man­u­fac­tur­ing and dis­tri­b­u­tion than we do about fin­ished dosage forms,” Throck­mor­ton said.

Ju­dith McMeekin

In re­sponse to crit­i­cisms over FDA’s prac­tice of no­ti­fy­ing for­eign fa­cil­i­ties in ad­vance of in­spec­tions, Ju­dith McMeekin, as­so­ciate com­mis­sion­er for reg­u­la­to­ry af­fairs at FDA’s Of­fice of Reg­u­la­to­ry Af­fairs (ORA) said that pre­an­nounc­ing in­spec­tions helps to avoid po­ten­tial re­fusals and con­serve FDA re­sources.

McMeekin al­so point­ed out that both for­eign and do­mes­tic man­u­fac­tur­ers are held to the same stan­dards and that FDA must deal with ju­ris­dic­tion­al dif­fer­ences in con­duct­ing for­eign in­spec­tions. Be­cause FDA does not have the same au­thor­i­ties that it does in the US when op­er­at­ing in oth­er coun­tries, the pre­an­nounce­ment process gives the agency a chance to doc­u­ment a firm’s agree­ment to al­low an in­spec­tion, McMeekin said. When a for­eign firm re­fus­es an in­spec­tion, FDA may take oth­er ac­tions to ad­dress the safe­ty of the US drug sup­ply, such as plac­ing the firm on Im­port Alert.

“The FDA does not draw up­on the same en­force­ment mech­a­nisms or have a com­pa­ra­ble lev­el of in­fra­struc­ture,” McMeekin said, not­ing that in the US the agency can seek a war­rant if a firm re­fus­es in­spec­tion.

McMeekin al­so lat­er clar­i­fied that FDA does con­duct some unan­nounced in­spec­tions in oth­er coun­tries, but they are typ­i­cal­ly for-cause in­spec­tions. She said she does not know how many unan­nounced in­spec­tions the agency con­duct­ed in In­dia and Chi­na in 2019.

Mary Deni­gan-Macauley

How­ev­er, GAO’s Mary Deni­gan-Macauley told sen­a­tors that GAO feels “that unan­nounced in­spec­tions are very im­por­tant … but they are very few and it does raise ques­tions about the equiv­a­len­cy to what we do here in the Unit­ed States.” In 2018, GAO found that on­ly a small per­cent­age of in­spec­tions car­ried out by FDA’s Chi­na and In­dia of­fice in­ves­ti­ga­tors were unan­nounced or con­duct­ed on short no­tice, while most of FDA’s for­eign in­spec­tions were car­ried out by US-based in­ves­ti­ga­tors and were typ­i­cal­ly pre­an­nounced 12 weeks in ad­vance.

When asked by Sen. Mag­gie Has­san (D-NH) about FDA’s de­ci­sion to halt for­eign in­spec­tions amid the COVID-19 pan­dem­ic, Deni­gan-Macauley said that, “The fact that [for­eign in­spec­tions have] stopped – I un­der­stand the need for be­ing able to pro­tect their own peo­ple – but it is con­cern­ing and I would want to en­sure that the oth­er steps that they have in place are rig­or­ous.”

Has­san re­spond­ed by say­ing she be­lieves “FDA’s de­ci­sion to cur­tail in­spec­tions is in­ap­pro­pri­ate.”


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Reimagining cancer treatments

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Justin Klee (L) and Joshua Cohen, Amylyx co-CEOs (Cody O'Loughlin/The New York Times; courtesy Amylyx)

Ad­vo­cates, ex­perts cry foul over Amy­lyx's new ALS drug, cit­ing is­sues with price, PhI­II com­mit­ment

Not 24 hours after earning the first ALS drug approval in five years, Amylyx Pharmaceuticals’ Relyvrio is already drawing scrutiny. And it’s coming from multiple fronts.

In an investor call Friday morning, Amylyx revealed that it would charge about $158,000 per year, a price point that immediately drew backlash from ALS advocates and some outside observers. The cost reveal had been highly anticipated in the immediate hours after Thursday evening’s approval, though Amylyx only teased Relyvrio would cost less than previously approved drugs.

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Land­mark Amy­lyx OK spurs de­bate; Some... pos­i­tive? Alzheimer's da­ta; Can­cer tri­al bot­tle­neck; Sanofi's CRISPR bet; 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.

After brief stops in Paris and Boston, John Carroll and the Endpoints crew are staying on the road in October with their return for a live/streaming EUBIO22 in London. The hybrid event fireside chats and panels on mRNA, oncology and the crazy public market. We hope you can join him there.

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Joshua Cohen (L) and Justin Klee, Amylyx co-CEOs

Up­dat­ed: Af­ter long and wind­ing road, FDA ap­proves Amy­lyx's ALS drug in vic­to­ry for pa­tients and ad­vo­ca­cy groups

For just the third time in its 116-year history, the FDA has approved a new treatment for Lou Gehrig’s disease, or ALS.

US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Up­dat­ed: Al­ny­lam re­in­forces APOL­LO-B patisir­an da­ta be­fore head­ing to the FDA

Weeks after uncorking some mostly positive data for patisiran in transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy, Alnylam is bolstering its package with new exploratory and subgroup data before shipping it off to regulators.

The RNAi drug maintained “generally consistent” benefits in efficacy and quality of life across several prespecified subgroups at month 12, Alnylam announced on Friday afternoon, including age, baseline tafamidis use, ATTR amyloidosis type, baseline six-minute walk test score and others.

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#AAO22: J&J’s first look at com­mon eye dis­ease port­fo­lio pads the case for PhII of gene ther­a­py

CHICAGO — While the later-stage drug developers in the geographic atrophy field are near the finish line, Johnson & Johnson’s Janssen is taking a more deliberate route, with a treatment that it hopes to be a one-time fix.

The Big Pharma will take its Hemera Biosciences-acquired gene therapy into a Phase II study later this year in patients with GA, a common form of age-related macular degeneration that impacts about five million people worldwide. To get there, Janssen touted early-stage safety data at the American Academy of Ophthalmology annual conference Saturday morning, half a day after competitors Apellis and Iveric Bio revealed their own more-detailed Phase III analyses.

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Jerome Durso, Intercept Pharmaceuticals CEO

In­ter­cep­t's OCA fails a PhI­II NASH tri­al, rais­ing fresh doubts about its years­long quest for an OK

Intercept Pharmaceuticals has run into another big setback in its yearslong quest to win an approval for OCA in NASH. The biotech put out word Friday morning that its Phase III REVERSE study failed the primary endpoint for the liver disease, sending its share price into a tailspin.

There was no significant improvement in fibrosis among the patients suffering from cirrhosis who were treated with obeticholic acid, with investigators hunting for a minimum 1-stage histological improvement in the disease after 18 months of therapy.

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Bo Cumbo, new Solid Bio CEO

Sol­id Bio gets a new CEO, $75M cash and drops lead drug as big in­vestors ju­ry-rig a merg­er deal

Three months after Endpoints News broke the story that gene therapy outfit AavantiBio had gutted its CMC group in a reorganization, the biotech’s CEO has helped engineer a merger with struggling penny stock player Solid Bio. And he’s going to remain in charge of the combined operation, as Solid founder Ilan Ganot steps aside.

The merger news this morning features some high-profile investors.

Perceptive Advisors, RA Capital Management and Bain Capital Life Sciences are leading a $75 million raise to add to the pool of cash Solid will have after the tie-up. That will leave Solid $215 million in cash as Bain’s Adam Koppel jumps on the board — enough to pay for ops and get through some key data milestones on their way into 2025.

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