FDA scut­tles blue­bird's ac­cel­er­at­ed plans for sick­le cell gene ther­a­py, as high­er CMC bar forces 1-year de­lay

In yet an­oth­er smudge on blue­bird bio’s track record for ex­e­cu­tion, the biotech is push­ing back the fil­ing for its gene ther­a­py in sick­le cell dis­ease by a year due to a new da­ta re­quire­ment from the FDA.

With the set­back, blue­bird joins a league of gene ther­a­py de­vel­op­ers — from Bio­Marin to Voy­ager — that have been ham­pered by CMC is­sues. While some­what un­ex­pect­ed, the reg­u­la­tors’ re­quest high­lights their strin­gency around man­u­fac­tur­ing and qual­i­ty con­trol.

Ac­cord­ing to blue­bird, while the FDA is hap­py to base its re­view on promis­ing da­ta from Group C of the HGB-206 study, it want­ed more in­for­ma­tion on the re­fined man­u­fac­tur­ing process the biotech is plan­ning to use for the com­mer­cial batch of bb1111. In short, blue­bird will need to prove “an­a­lyt­i­cal com­pa­ra­bil­i­ty” as it tran­si­tions from clin­i­cal-grade to com­mer­cial-grade man­u­fac­tur­ing.

“(FDA) re­quest­ed the use of drug prod­uct man­u­fac­tured from sick­le cell dis­ease (SCD) pa­tient cells in ad­di­tion to healthy donors as well as com­mer­cial lentivi­ral vec­tor to demon­strate drug prod­uct com­pa­ra­bil­i­ty,” the com­pa­ny not­ed.

That re­quires blue­bird to get drug prod­uct from its com­mer­cial con­tract man­u­fac­tur­ing or­ga­ni­za­tion, which is it­self ex­pe­ri­enc­ing 4 to 6 month de­lays re­lat­ed to Covid-19. Once they se­cure a slot, the whole process is ex­pect­ed to take 6 months — mean­ing the BLA fil­ing will hap­pen in late 2022 the ear­li­est.

The im­pli­ca­tions of this de­lay will re­ver­ber­ate across blue­bird’s en­tire pipeline, wrote Yaron Wer­ber at Cowen.

“As BLUE is a SCD sto­ry longer-term, this puts pres­sure on ide-cel’s launch in Q2:21 to per­form,” he wrote, adding: “The FDA’s re­quest in SCD ap­pears un­like­ly to im­pact the fil­ing in TDT which re­mains on track for mid-’21.”

Both the sick­le cell dis­ease and trans­fu­sion-de­pen­dent be­ta-tha­lassemia pro­grams are built up­on Lenti­Glo­bin, which de­liv­ers a func­tion­al copy of the HBB gene in­to a pa­tient’s own hematopoi­et­ic stem cells us­ing a lentivi­ral vec­tor.

De­spite nab­bing ap­proval in Eu­rope for TDT last June, the com­pa­ny post­poned the launch un­til the be­gin­ning of 2020 in or­der to fi­nal­ize com­mer­cial spec­i­fi­ca­tions. Mar­ket­ed as Zyn­te­glo in Eu­rope, the gene ther­a­py has yet to treat its first com­mer­cial pa­tients. The pan­dem­ic has held it back even more, along­side a US fil­ing orig­i­nal­ly planned for ear­li­er this year.

“When asked if dif­fer­ent dis­ease char­ac­ter­is­tics of SCD vs TDT trig­ger this lev­el of com­plex­i­ty of reg­u­la­to­ry path, mgmt agreed up­on and al­so brought up scale-up of man­u­fac­tur­ing for larg­er mar­ket op­py of SCD as an­oth­er fac­tor, and the need to tran­si­tion to a more com­mer­cial friend­ly process in SCD,” Jef­feries’ Biren Amin not­ed.

But man­u­fac­tur­ing strug­gles have long been an is­sue at blue­bird. Back in March the agency had al­so punt­ed back an ap­pli­ca­tion for ide-cel, the BC­MA CAR-T part­nered with Bris­tol My­ers Squibb via Cel­gene, be­cause of a faulty sec­tion on CMC. The teams have since re­filed and scored pri­or­i­ty re­view.

Some in­vestors, though, are not wait­ing around for blue­bird to fig­ure out the sick­le cell pro­gram. Shares $BLUE tum­bled 13.63% pre-mar­ket to $ 50.57.

Biogen CEO Michel Vounatsos (via Getty Images)

With ad­u­canum­ab caught on a cliff, Bio­gen’s Michel Vounatsos bets bil­lions on an­oth­er high-risk neu­ro play

With its FDA pitch on the Alzheimer’s drug aducanumab hanging perilously close to disaster, Biogen is rolling the dice on a $3.1 billion deal that brings in commercial rights to one of the other spotlight neuro drugs in late-stage development — after it already failed its first Phase III.

The big biotech has turned to Sage Therapeutics for its latest deal, close to a year after the crushing failure of Sage-217, now dubbed zuranolone, in the MOUNTAIN study.

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Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

Af­ter Ko­dak de­ba­cle, US lends $1.1B to a syn­thet­ic bi­ol­o­gy com­pa­ny and their big Covid-19, mR­NA plans

In mid-August, as Kodak’s $765 million government-backed push into drug manufacturing slowly fell apart in national headlines, Ginkgo Bioworks CEO Jason Kelly got a message from his company’s government liaison: HHS wanted to know if they, too, might want a loan.

The government’s decision to lend Kodak three quarters of a billion dollars raised eyebrows because Kodak had never made drugs before. But Ginkgo, while not a manufacturing company, had spent the last decade refining new ways to produce materials inside cells and building automated facilities across Boston.

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Pascal Soriot (AP Images)

As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

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The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

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John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Al­ny­lam gets the green light from the FDA for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1. The news comes just 4 days after the European Commission took the lead in offering a green light.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

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FDA hands Liq­uidia and Re­vance a CRL and de­fer­ral, re­spec­tive­ly, as Covid-19 cre­ates in­spec­tion chal­lenge

Two biotechs said they got turned away by the FDA on Wednesday, in part due to pandemic-related travel restrictions.

North Carolina-based Liquidia Technologies was handed a CRL for its lead pulmonary arterial hypertension drug, citing the need for more CMC data and on-site pre-approval inspections, which the FDA hasn’t been able to conduct due to travel restrictions. The agency also deferred its decision on Revance Therapeutics’ BLA for its frown line treatment, because it needs to inspect the company’s northern California manufacturing facility. The action, Revance emphasized, was not a CRL.

Bax­ter con­tin­ues on-shoring push with $50M In­di­ana ex­pan­sion

It’s been a banner year for the once humdrum business of manufacturing drugs, particularly vaccines. Billions have been spent ramping up facilities for Covid-19 jabs, while individual CDMOs have expanded their facilities, apparently anticipating demand or responding to a government-led push to onshore drug manufacturing.

Now Baxter Biopharma Solutions, the CDMO wing of the many-armed healthcare giant Baxter, is getting in on the game. On Tuesday, they announced plans to spend $50 million to expand their flagship, 600,000 square-foot facility in Bloomington, IN.

Leonard Schleifer, Regeneron CEO (Andrew Harnik/AP)

Trail­ing Eli Lil­ly by 12 days, Re­gen­eron gets the FDA OK for their Covid-19 an­ti­body cock­tail

A month and a half after becoming the experimental treatment of choice for a newly diagnosed president, Regeneron’s antibody cocktail has received emergency use authorization from the FDA. It will be used to treat non-hospitalized Covid-19 patients who are at high-risk of progressing.

Although the Rgeneron drug is not the first antibody treatment authorized by the FDA, the news comes as a significant milestone for a company and a treatment scientists have watched closely since the outbreak began.

The flu virus (CDC)

Roche tacks on an­oth­er Xofluza in­di­ca­tion as flu sea­son meets pan­dem­ic

Xofluza was heralded as the first new flu drug in 20 years when it got the FDA OK back in 2018. But even so, Roche saw tough competition from cheaper Tamiflu generics that appeared to be nearly as — if not just as — effective.

Now, the pharma says the drug also can be used to prevent influenza after exposure, snagging a new approval and adding to Xofluza’s appeal as flu season meets the pandemic.