Sus­pend­ed Cal­i­for­nia cell ther­a­py man­u­fac­tur­ing site hit with FDA warn­ing let­ter over ma­jor qual­i­ty con­cerns

A cell ther­a­py out­fit in Cal­i­for­nia that man­u­fac­tures a hu­man um­bil­i­cal cord de­rived cel­lu­lar prod­uct and ex­o­some prod­ucts is fac­ing a warn­ing from the FDA over sev­er­al ma­jor ob­ser­va­tions re­lat­ed to qual­i­ty.

The FDA notes the site’s “de­fi­cient donor screen­ing prac­tices, in­ad­e­quate asep­tic prac­tices, un­val­i­dat­ed man­u­fac­tur­ing,” and the “risk that your prod­ucts may be con­t­a­m­i­nat­ed with mi­croor­gan­isms or have oth­er se­ri­ous prod­uct qual­i­ty de­fects.”

In­vit­rx Ther­a­peu­tics re­ceived the warn­ing let­ter ear­li­er this month for its site in Lake For­est, CA, which was in­spect­ed in March and lat­er halt­ed some man­u­fac­tur­ing.

The let­ter, which had 10 ma­jor ob­ser­va­tions, states that In­vit­rx had failed to de­ter­mine and doc­u­ment the el­i­gi­bil­i­ty of a cell or tis­sue donor based up­on the re­sults of screen­ing and test­ing and not­ed that it had not re­viewed “rel­e­vant med­ical records” it re­ceived from the um­bil­i­cal cord tis­sue sup­pli­ers to de­ter­mine el­i­gi­bil­i­ty.

The let­ter al­so re­vealed that since op­er­a­tions be­gan, In­vit­rx has “failed to de­ter­mine and doc­u­ment the el­i­gi­bil­i­ty of hun­dreds of tis­sue donors.” Tis­sues from these donors were re­port­ed to be used to man­u­fac­ture prod­ucts.

The agency al­so not­ed that In­vit­rx had failed to val­i­date the asep­tic process to man­u­fac­ture sev­er­al of its prod­ucts, with in­ves­ti­ga­tors al­so ob­serv­ing “pri­ma­ry prod­uct con­tain­ers” for items that are sup­posed to be ster­ile be­ing stored on a shelf in an “open bag” in the clean­room. Caps that are re­ceived in bulk al­so did not have fur­ther clean­ing or ster­il­iza­tion.

As for the site’s en­vi­ron­men­tal mon­i­tor­ing pro­ce­dures, the let­ter said that In­vit­rx did not per­form en­vi­ron­men­tal mon­i­tor­ing of its asep­tic pro­cess­ing area or have writ­ten pro­ce­dures in place at the time of in­spec­tion.

Two-year ex­pi­ra­tion dates for some prod­ucts were set with­out sup­port­ing da­ta and in­cu­ba­tors used for “steril­i­ty test­ing” were al­so not qual­i­fied for that use. Sev­er­al oth­er QC is­sues in­volv­ing writ­ten pro­ce­dures and oth­er test­ing were al­so not­ed.

The FDA said that “cor­rec­tive ac­tions” had been tak­en and sus­pend­ed all clin­i­cal drug sub­stance man­u­fac­tur­ing and drug prod­uct batch­es at the Lake For­est fa­cil­i­ty “in­tend­ed for use in do­mes­tic clin­i­cal tri­als.” How­ev­er, this is not en­tire­ly sat­is­fac­to­ry for the FDA.

“It is un­clear from this state­ment whether you have sus­pend­ed the man­u­fac­tur­ing of all prod­ucts iden­ti­fied in the FDA-483. Fur­ther, it is un­clear, based on your re­sponse, whether you will man­u­fac­ture your prod­ucts at any of your oth­er lo­ca­tions for dis­tri­b­u­tion. Your re­sponse al­so de­scribes ‘in­ter­im con­trol[s]’ you plan to im­ple­ment pri­or to com­plet­ing cer­tain cor­rec­tive ac­tions, which sug­gests that In­vit­rx will re­sume man­u­fac­tur­ing pri­or to ad­e­quate­ly ad­dress­ing the ex­ist­ing de­fi­cien­cies,” the let­ter said.

It is al­so not­ed that the FDA can­not ful­ly as­sess the com­pa­ny’s re­spons­es to sev­er­al of the ob­ser­va­tions as they do not pro­vide suf­fi­cient de­tails on the “cor­rec­tive ac­tions,” and they lack a time­line for the com­ple­tion of all the ac­tions. The re­sponse al­so does not prop­er­ly ad­dress the fail­ure to have an IND in ef­fect for clin­i­cal in­ves­ti­ga­tions of In­vit­rx’s prod­ucts. How­ev­er, In­vit­rx is com­mit­ted to re­call­ing dis­trib­uted prod­ucts.

In­vit­rx has been pulled in­to a “reg­u­la­to­ry meet­ing” with the FDA to dis­cuss the steps that have been tak­en since the March in­spec­tion. The meet­ing is on the books for the mid­dle of De­cem­ber.

End­points News reached out to In­vit­rx for a state­ment on the let­ter but did not re­ceive a re­sponse by press time.

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Raul Rodriguez, Rigel Pharma CEO

Rigel Phar­ma scores FDA ap­proval for leukemia, kick­ing off show­down with Servi­er in IDH1

When Rigel Pharma bought olutasidenib from Forma Therapeutics, it acquired a drug that already secured a PDUFA date at the FDA — for February 2023. But regulators are ready to give their OK sooner than that.

The FDA has approved the IDH1 inhibitor as a treatment for adult patients with relapsed or refractory acute myeloid leukemia who have a susceptible IDH-1 (isocitrate dehydrogenase-1) mutation as detected by an FDA-greenlit test. Rigel will market it as Rezlidhia.

Tim Pearson, Carrick Therapeutics CEO

Pfiz­er backs $60M in­fu­sion in­to Car­rick, teams up on breast can­cer treat­ment

In a big week for Carrick Therapeutics, the company announced $60 million in funding for its lead breast cancer drug and development of a second program, as well as a collaboration with Pfizer for combo development.

The $35 million from Pfizer comes with an agreement under which Pfizer will support Carrick’s Phase II study of samuraciclib in combination with Pfizer’s Faslodex for advanced breast cancer. Along with the investment, Adam Schayowitz, vice president and development head of breast cancer, colorectal cancer and melanoma at Pfizer global product development, will join Carrick’s scientific advisory board.

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Paul Hudson, Sanofi CEO (ROMUALD MEIGNEUX/Sipa via AP Images)

Sanofi and Am­gen are bring­ing cash to cov­er the ta­ble stakes for the Hori­zon M&A game

With the market cap on Horizon Therapeutics $HZNP pushed up to the $23 billion mark today, one of the Big Pharmas in the hunt for a major league buyout deal signaled it’s playing the M&A game with cash.

Paris-based Sanofi, where CEO Paul Hudson has been largely focused on some risky biotech acquisitions to win some respect for its future pipeline prospects, issued a statement early Friday — complying with rule 2.12 of the Irish takeover rules — making clear that while the certainty or size of an offer can’t be determined, any offer “will be solely in cash.” And Amgen CEO Robert Bradway came right in behind him, filing a statement on the London Stock Exchange overnight that any offer they may make will “likely” be in cash as well.

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Philip Tagari switch­es Am­gen's dis­cov­ery lab for in­sitro's ma­chine learn­ing tools; CEO Joaquin Du­a­to to chair J&J's board

In February, Philip Tagari will take a few days of retirement and then immediately return to industry. He won’t be leading the therapeutics discovery unit for a large biopharma, though.

He’ll trade in his Amgen hat for chief scientist at a machine learning startup that has reeled in hundreds of millions in capital to lay the groundwork for a much-hyped new model of drug discovery that aims to speed up the time to new clinical assets.

Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls

Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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Lynn Baxter, Viiv Healthcare's head of North America

Vi­iV dri­ves new cor­po­rate coali­tion in­clud­ing Uber, Tin­der and Wal­mart, aimed at end­ing HIV

ViiV Healthcare is pulling together an eclectic coalition of consumer businesses in a new White House-endorsed effort to end HIV by the end of the decade.

The new US Business Action to End HIV includes pharma and health companies — Gilead Sciences, CVS Health and Walgreens — but extends to a wide range of consumer companies that includes Tinder, Uber and Walmart.

ViiV is the catalyst for the group, plunking down more than half a million dollars in seed money and taking on ringmaster duties for launch today on World AIDS Day, but co-creator Health Action Alliance will organize joint activities going forward. ViiV and the alliance want and expect more companies to not only join the effort, but also pitch in funding.

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Roche HQ in Basel, Switzerland. (Image credit: Kyle LaHucik/Endpoints News)

As com­peti­tors near FDA goal­post, Roche spells out its re­peat Alzheimer's set­back

Before Roche can turn all eyes on a new version of its more-than-once-failed Alzheimer’s drug gantenerumab, the Big Pharma had to flesh out data on the November topline failure at an annual conference buzzier than in years past thanks to hotly watched rivals in the field: Eisai and Biogen’s lecanemab, and Eli Lilly’s donanemab.

There was less than a 10% difference between Roche’s drug and placebo at slowing cognitive decline across two Phase III trials, which combined enrolled nearly 2,000 Alzheimer’s patients. In its presentation at the conference Wednesday, Roche said it saw less sweeping away of toxic proteins than it had anticipated. For years, researchers and investors have put their resources behind the idea that more amyloid removal would equate to reduced cognitive decline.

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