FDA warns Take­da over asep­tic pro­cess­ing, in­ad­e­quate in­ves­ti­ga­tions

The FDA last week warned Japan­ese drug­mak­er Take­da over good man­u­fac­tur­ing prac­tice (GMP) vi­o­la­tions ob­served dur­ing an in­spec­tion of its Hikari, Ya­m­aguchi fa­cil­i­ty last No­vem­ber.

Specif­i­cal­ly, the warn­ing let­ter cites the firm for three vi­o­la­tions re­lat­ing to its pro­ce­dures for asep­tic man­u­fac­tur­ing and in­ves­ti­ga­tions in­to un­ex­plained dis­crep­an­cies and equip­ment mal­func­tions.

“Our in­spec­tion found that your Qual­i­ty Unit (QU) did not take ap­pro­pri­ate steps pri­or to re­sump­tion of asep­tic man­u­fac­tur­ing af­ter a shut­down that in­clud­ed mul­ti­ple sig­nif­i­cant ac­tiv­i­ties that com­pro­mised your clean­room con­trol,” FDA writes.

FDA says the com­pa­ny al­lowed man­u­fac­tur­ing op­er­a­tions to re­sume with­out per­form­ing me­dia fills as re­quired in its pro­ce­dures and shipped mul­ti­ple batch­es of af­fect­ed prod­ucts to the US.

While Take­da com­mit­ted to per­form­ing asep­tic process sim­u­la­tion for the af­fect­ed man­u­fac­tur­ing line, it stat­ed that, “There was no ad­verse im­pact to prod­uct be­cause [its] pro­ce­dure for restart­ing pro­duc­tion re­quires that en­vi­ron­men­tal mon­i­tor­ing da­ta and util­i­ty re­sults are avail­able be­fore prod­uct re­lease.”

How­ev­er, FDA says this is in­ad­e­quate, “Be­cause you failed to ad­e­quate­ly as­sess the im­pact of steril­i­ty as­sur­ance of the prod­ucts man­u­fac­tured in a fa­cil­i­ty af­ter a shut­down in which clean­room con­trol was com­pro­mised.”

In ad­di­tion to a risk as­sess­ment for the prod­ucts dis­trib­uted with­out ad­e­quate as­sur­ance of asep­tic pro­cess­ing con­di­tions, FDA says it wants Take­da to pro­vide a “com­pre­hen­sive as­sess­ment and re­me­di­a­tion plan” to en­sure its QU has the au­thor­i­ty and re­sources to func­tion ef­fec­tive­ly, as well as a “de­scrip­tion of how top man­age­ment sup­ports qual­i­ty as­sur­ance and re­li­able op­er­a­tions.

The warn­ing let­ter al­so notes that Take­da “failed to es­tab­lish and fol­low ap­pro­pri­ate writ­ten pro­ce­dures that are de­signed to pre­vent mi­cro­bial con­t­a­m­i­na­tion of drug prod­ucts pur­port­ing to be ster­ile.”

Ad­di­tion­al­ly, FDA says its in­ves­ti­ga­tors ob­served poor asep­tic be­hav­ior at the fa­cil­i­ty, in­clud­ing staff fail­ing to “san­i­tize gloved hands af­ter touch­ing sur­faces such as cur­tains and com­put­er touch­screens,” and per­form­ing ma­nip­u­la­tions with “rapid move­ments, rather than slow and de­lib­er­ate asep­tic tech­nique.”

Last­ly, the warn­ing let­ter says Take­da, “Lacked ad­e­quate in­ves­ti­ga­tions in­to equip­ment mal­func­tions. Sev­er­al in­ves­ti­ga­tions were con­clud­ed with­out suf­fi­cient­ly ad­dress­ing root caus­es or en­sur­ing ad­e­quate scope, al­low­ing man­u­fac­tur­ing risks to per­sist for ex­tend­ed pe­ri­ods.”

In one case, FDA says Take­da did not ad­e­quate­ly in­ves­ti­gate the oc­cur­rence of “black par­ti­cles” in mul­ti­ple batch­es of vials for one of its prod­ucts. In an­oth­er, the agency says the com­pa­ny used mal­func­tion­ing equip­ment “for a pro­tract­ed pe­ri­od to ster­il­ize com­po­nents of [its] in­jectable prod­uct.”


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Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

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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