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.

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

Onno van de Stolpe, Galapagos CEO (Thierry Roge/Belga Mag/AFP via Getty Images)

Gala­pa­gos chops in­to their pipeline, drop­ping core fields and re­or­ga­niz­ing R&D as the BD team hunts for some­thing 'trans­for­ma­tive'

Just 5 months after Gilead gutted its rich partnership with Galapagos following a bitter setback at the FDA, the Belgian biotech is hunkering down and chopping the pipeline in an effort to conserve cash while their BD team pursues a mission to find a “transformative” deal for the company.

The filgotinib disaster didn’t warrant a mention as Galapagos laid out its Darwinian restructuring plans. Forced to make choices, the company is ditching its IPF molecule ’1205, while moving ahead with a Phase II IPF study for its chitinase inhibitor ’4617.

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UP­DAT­ED: EMA safe­ty com­mit­tee seeks more in­fo on heart in­flam­ma­tion fol­low­ing Pfiz­er Covid-19 vac­cine

The European Medicines Agency’s safety committee said Friday that it’s aware of cases of inflammation of the heart muscle and inflammation of the membrane around the heart, mainly reported following vaccination with Pfizer’s Covid-19 vaccine, known in Europe as Comirnaty.

“There is no indication that these cases are due to the vaccine,” the EMA’s Pharmacovigilance Risk Assessment Committee said.

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Stéphane Bancel, Getty

Mod­er­na CEO brush­es off US sup­port for IP waiv­er, eyes more than $19B in Covid-19 vac­cine sales in 2021

Moderna is definitively more concerned with keeping pace with Pfizer in the race to vaccinate the world against Covid-19 than it is with Wednesday’s decision from the Biden administration to back an intellectual property waiver that aims to increase vaccine supplies worldwide.

In its first quarter earnings call on Thursday, Moderna CEO Stéphane Bancel shrugged off any suggestion that the newly US-backed intellectual property waiver would impact his company’s vaccine or bottom line. Still, the company’s stock price fell by about 9% in early morning trading.

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Ad­comm splits slight­ly in fa­vor of FDA ap­prov­ing Chemo­Cen­tryx’s rare dis­ease drug

The FDA’s Arthritis Advisory Committee on Thursday voted 10 for and 8 against the approval of ChemoCentryx’s $CCXI investigational drug avacopan as a treatment for adults with a rare and serious disease known as anti-neutrophil cytoplasmic autoantibody (ANCA)-vasculitis.

The vote on whether the FDA should approve the drug was preceded by a split vote of 9 to 9 on whether the efficacy data support approval, and 10 to 8 that the safety profile of avacopan is adequate enough to support approval.

Angela Merkel (AP Photo/Michael Sohn)

Covid-19 roundup: Pfiz­er sub­mits vac­cine for full ap­proval; Merkel op­pos­es Biden pro­pos­al to sus­pend IP for vac­cines

Pfizer and BioNTech said Friday that they’ve submitted a biologics license application to the FDA for full approval of their mRNA vaccine for those over the age of 16.

How long it will take the FDA to decide on the BLA will be set once it’s been formally accepted by the agency.

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, previously told Endpoints News that the review of the BLA should take between three and four months, but it may be even faster than that.

As­traZeneca caps PD-L1/CT­LA-4/chemo com­bo come­back with OS win. Is treme­li­mum­ab fi­nal­ly ready for ap­proval?

AstraZeneca’s closely-watched POSEIDON study continues to be the rare bright spot in its push for an in-house PD-L1/CTLA-4 combo.

Combining Imfinzi and tremelimumab with physicians’ choice of chemotherapy helped patients with stage IV non-small cell lung cancer live longer, the company reported — marking the first time the still-experimental tremelimumab has demonstrated an OS benefit.

For AstraZeneca and CEO Pascal Soriot, the positive readout — which is devoid of numbers — offers much-needed validation for the big bet they made on Imfinzi plus tremelimumab, after the PD-L1/CTLA-4 regimen failed multiple trials in head and neck cancer as well as lung cancer.

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Ron DePinho (file photo)

A 'fly­over' biotech launch­es in Texas with four Ron De­Pin­ho-found­ed com­pa­nies un­der its belt

In his 13 years at Genzyme, Michael Wyzga noticed something about East Coast drugmakers. Execs would often jet from Boston or New York to San Francisco to find more assets, and completely miss the work being done in flyover states, like Texas or Wisconsin.

“If it doesn’t come out of MGH or MIT or Harvard, probably not that interesting,” he said of the mindset.

Now, he and some well-known industry players are looking to change that, and they’ve reeled in just over $38 million to do it.

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An­oth­er failed tri­al for Or­p­hazyme's 'pipeline-in-a-pro­duc­t' leaves shad­ow on drug's fu­ture

The tumultuous ride for Orphazyme continued on Friday as the company announced that a pivotal trial for its lead drug arimoclomol failed yet again, this time in the treatment of ALS, seeding doubt in a drug that had recently been cleared by the FDA for priority review. The latest failure casts a darker shadow on the upcoming decision despite Orphazyme’s upbeat outlook.

In a statement, the Danish biotech announced that the drug did not meet its primary or secondary endpoints evaluating function and survival. But the company has not announced any data surrounding the failure, instead saying that it will publish the complete results later this year.