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.

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.

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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Vi­a­tris with­draws ac­cel­er­at­ed ap­proval for top­i­cal an­timi­cro­bial 24 years lat­er

After 24 years without confirming clinical benefit, the FDA announced Tuesday morning that Viatris (formed via Mylan and Pfizer’s Upjohn) has decided to withdraw a topical antimicrobial agent, Sulfamylon (mafenide acetate), after the company said conducting a confirmatory study was not feasible.

Sulfamylon first won FDA’s accelerated nod in 1998 as a topical burn treatment, with the FDA noting that last December, Mylan told the agency that it wasn’t running the trial.

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Tim Van Hauwermeiren, argenx CEO

Ar­genx pur­chas­es $100M+ FDA pri­or­i­ty re­view vouch­er from blue­bird bio

Argenx’s Vyvgart is due for a speedy review at the FDA, thanks to a $102 million priority review voucher (PRV).

The Netherland-based biotech picked up the PRV from bluebird bio, the companies announced on Wednesday. PRVs shorten a drug’s FDA review period from 10 months to 6 months, though they often sell on the open market for around $100 million each.

Argenx plans on using the express ticket on efgartigimod, its neonatal Fc receptor (FcRn) blocker marketed as Vyvgart for adults with generalized myasthenia gravis (gMG). While Vyvgart won its first approval last December for the chronic neuromuscular disease — which is characterized by difficulties with facial expression, speech, swallowing and breathing — CEO Tim Van Hauwermeiren said in a news release that he plans to “be active in fifteen disease targets by 2025.”

Lex­i­con slams FDA over hear­ing de­nial fol­low­ing a CRL for its SGLT2 in­hibitor can­di­date

Lexicon Pharmaceutical is not giving up on its Type I diabetes candidate, despite FDA’s repeated rejections. This week the company laid out is argument again for a hearing on sotagliflozin in response to the FDA’s most recent denial.

The issue goes back to March 2019 when the FDA made very clear to Lexicon and its now departed partner Sanofi that it would not approve their application for a potential Type I diabetes drug because it does not appear to be safe.

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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Matt Gline, Roivant Sciences CEO (Photo by John Sciulli/Getty Images for GLG)

Pfiz­er and Roivant team up again for an­oth­er 'Van­t', set­ting up an­ti-in­flam­ma­to­ry show­down with Prometheus

Pfizer and Roivant are teaming up to launch a new ‘Vant’ aimed at bringing a mid-stage anti-inflammatory drug to market, the pair announced Thursday.

There’s no name for the startup yet, nor are there any employees. Thus far, the new company and Roivant can be considered “one and the same,” Roivant CEO Matt Gline tells Endpoints News. But Pfizer is so enthusiastic about the target that it elected to keep 25% of equity in the drug rather than take upfront cash from Roivant, Gline said.

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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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