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.

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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Mihael Polymeropoulos, Vanda Pharmaceuticals CEO

Phar­ma com­pa­ny con­tin­ues its FDA law­suit spree, this time af­ter agency de­nies fast-track des­ig­na­tion

Vanda Pharmaceuticals is making a name for itself, at least in terms of suing the FDA.

The DC-headquartered firm on Monday filed its latest suit against the agency, with the company raising concerns over the FDA’s failure to grant a fast track designation for Vanda’s potential chronic digestive disorder drug tradipitant, which is a neurokinin 1 receptor antagonist.

Specifically, Vanda said FDA’s “essential point” in its one-page denial letter on the designation pointed to “the lack of necessary safety data,” which was “inconsistent with the criteria for … Fast Track designation.”

Robert Califf (Michael Brochstein/Sipa USA via AP Images)

House Re­pub­li­cans at­tack Chi­na-on­ly da­ta in FDA sub­mis­sions, seek new in­ves­ti­ga­tion in­to re­search in­spec­tions

Three Republican representatives are calling on the FDA to take a closer look at the applications including only clinical data from China.

The letter to FDA commissioner Rob Califf late last week comes as the agency recently rejected Eli Lilly’s anti-PD-1 antibody, which attempted to bring China-only data but ran into a bruising adcomm that may crush the hopes of any other companies looking to bring cheaper follow-ons based only on Chinese data.

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Janet Woodcock (Greg Nash/Pool via AP Images)

'I re­al­ly don’t look back': Janet Wood­cock on her tran­si­tion away from drugs

Janet Woodcock may have one of the most historically long and drug-intense tenures in FDA history, but her new role is outside of all things pharma and the once-acting FDA commissioner isn’t looking back.

“No I really don’t look back,” Woodcock told Endpoints News via email on Monday morning. “Yes I will be transitioning. Longer discussion on infrastructure needed.”

Mod­er­na seeks to dis­miss Al­ny­lam suit over Covid-19 vac­cine com­po­nent, claim­ing wrong venue

RNAi therapeutics juggernaut Alnylam Pharmaceuticals made a splash in March when it sued and sought money from both Pfizer and Moderna regarding their use of Alnylam’s biodegradable lipids, which Alnylam claims have been integral to the way both companies’ mRNA-based Covid-19 vaccines work.

But now, Moderna lawyers are firing back, telling the same Delaware district court that Alnylam’s claims can only proceed against the US government in the Court of Federal Claims because of the way the company’s contract is set up with the US government. The US has spent almost $10 billion on Moderna’s Covid-19 vaccine so far.

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Cracks in the fa­cade: Is phar­ma's pan­dem­ic ‘feel good fac­tor’ wan­ing?

The discordant effects of the Covid-19 pandemic on pharma reputation continues. While the overall industry still retains a respectable halo from its Covid-19 quick response and leadership, a new patient group study reveals a different story emerging in the details.

On one hand, US patient advocacy groups rated the industry higher-than-ever overall. More than two-thirds (67%) of groups gave the industry a thumbs up for 2021, a whopping 10 percentage point increase over the year before, according to the PatientView annual study, now in its 9th year.

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J. Kelly Ganjei, AmplifyBio CEO and president

Af­ter pri­vate and state in­vest­ment, Am­pli­fy­Bio plans to ex­pand to an­oth­er Colum­bus, OH lo­ca­tion

An Ohio-based biotech spinout is garnering even more investment and space even after only being around for about a year.

AmplifyBio, a CRO and R&D biotech, has received a nine-figure investment to expand its facilities to a second location in New Albany, a suburb of the state capital of Columbus.

The company is receiving an investment of around $150 million to establish a new 350,000-square-foot facility. With this investment, the company is also expected to create over 200 new jobs both at its new location and at an existing location in West Jefferson, another Columbus suburb. That location, which has 220,000-square-feet of space for the young biotech, is the headquarters for nonprofit Battelle, which spun out AmplifyBio last year.

Michael Corbo, Pfizer CDO of inflammation & immunology

UP­DAT­ED: Plan­ning ahead for crowd­ed ul­cer­a­tive col­i­tis mar­ket, Pfiz­er spells out PhI­II da­ta on $6.7B Are­na drug

Pfizer has laid out the detailed results behind its boast that etrasimod — the S1P receptor modulator at the center of its $6.7 billion buyout of Arena Pharma — is the winner of the class, potentially leapfrogging an earlier entrant from Bristol Myers Squibb.

Pivotal data from the ELEVATE program in ulcerative colitis — which consists of two Phase III trials, one lasting 52 weeks and the other just 12 weeks — illustrate an “encouraging balance of efficacy and safety,” according to Michael Corbo, chief development officer of inflammation & immunology at Pfizer. The company is presenting the results as a late breaker at Digestive Disease Week.

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Todd Zavodnick, Dermavant CEO

With top­i­cal ap­proval, Der­ma­vant looks to bring new stan­dard-of-care to plaque pso­ri­a­sis pa­tients

Dermavant CEO Todd Zavodnick has been plotting to upend the plaque psoriasis market for years now. And with the company’s first approval on Tuesday, he’s pulling the trigger.

The FDA on Tuesday approved Dermavant’s “cosmetically elegant” vanishing cream tapinarof, the first steroid-free topical medication in its class, now marketed as Vtama. And unlike other launches, which could take months, Zavodnick is ready to roll it out as early as next week.