Blue­bird bio may fi­nal­ly get a gene ther­a­py ap­proved in the US

Blue­bird bio may, at long last, get a gene ther­a­py ap­proved in the US.

The Cam­bridge, MA biotech an­nounced Mon­day that the FDA had ac­cept­ed and giv­en pri­or­i­ty re­view for Zyn­te­glo, its gene ther­a­py for the rare blood dis­or­der be­ta-tha­lassemia. The an­nounce­ment sets up an ex­pe­dit­ed FDA de­ci­sion by May 20, 2022.

A pri­or­i­ty re­view doesn’t guar­an­tee ap­proval, and more than a few re­cent biotechs have been spurned af­ter re­ceiv­ing the des­ig­na­tion, in­clud­ing In­cyte, Sesen, and Proven­tion. But it rep­re­sents a sub­stan­tial step for­ward for a ther­a­py that has seen re­peat­ed set­backs and a com­pa­ny that not long ago had an ap­pli­ca­tion slapped down with a refuse-to-file let­ter.

The ap­proval rate for can­di­dates giv­en FDA pri­or­i­ty re­view hov­ered be­tween around 70% and 90% be­tween 2011 and 2019, com­pared to a lit­tle over 60% for drugs giv­en the 10-month stan­dard re­views.

Nick Leschly

The ac­cep­tance is a long time com­ing for blue­bird. The com­pa­ny showed its first re­sults from a Phase III tri­al in be­ta-tha­lassemia back in June 2017 and it first won con­di­tion­al ap­proval in Eu­rope in June 2019. Blue­bird at the time al­so showed dra­mat­ic da­ta on a sim­i­lar one-time treat­ment for sick­le cell dis­ease, and then-CEO Nick Leschly said the com­pa­ny planned to launch the ther­a­py for be­ta-tha­lassemia in 2020 and for sick­le cell dis­ease in 2022.

But the com­pa­ny then faced re­peat­ed de­lays for both can­di­dates, strug­gling to fi­nal­ize its man­u­fac­tur­ing process or reach an agree­ment with reg­u­la­tors on how best to mea­sure the qual­i­ty of its prod­uct. Blue­bird’s arc be­came a para­ble for the im­por­tance of man­u­fac­tur­ing in gene ther­a­py, where treat­ments are so tech­ni­cal­ly com­plex that re­li­ably pro­duc­ing it at scale can be as so­phis­ti­cat­ed a chal­lenge as prov­ing it works.

The de­lays ap­peared to be part of what pushed the com­pa­ny to split in­to two, spin­ning off its can­cer di­vi­sion to a biotech called 2sev­en­ty, so blue­bird could put most of its re­sources be­hind get­ting its gene ther­a­pies for rare ge­net­ic dis­eases ap­proved.

Be­ta-tha­lassemia, af­fect­ing about 1 in 100,000 Amer­i­cans, isn’t ex­pect­ed to be a huge mar­ket for blue­bird in the US. But an ap­proval would be a key step to­ward blue­bird de­liv­er­ing on the promise it’s flashed for years.

It’s par­tic­u­lar­ly im­por­tant af­ter the biotech de­cid­ed to with­draw Zyn­te­glo, along with the rest of its gene ther­a­py port­fo­lio, from the Eu­ro­pean mar­ket, where there is a sig­nif­i­cant­ly larg­er pop­u­la­tion of be­ta-tha­lassemia pa­tients. The com­pa­ny said Eu­ro­pean gov­ern­ments were un­will­ing to pay a fair price for the treat­ment.

In Ger­many, the on­ly coun­try for which blue­bird has dis­closed de­tails, au­thor­i­ties of­fered $790,000 for the one-time treat­ment, with the pay­out mov­ing to $950,000 if the ther­a­py is still work­ing af­ter five years. The fig­ures are rough­ly in line with the $900,000 price tag an­a­lysts ex­pect­ed blue­bird to put on the ther­a­py pri­or to launch. Blue­bird want­ed $1.8 mil­lion paid over 5 years, with pay­outs con­di­tioned on a pa­tient’s re­sponse.

A spokesper­son for blue­bird, al­lud­ing to the com­pa­ny’s tur­bu­lent his­to­ry with pric­ing, said the com­pa­ny has not yet set a price for Zyn­te­glo in the US and won’t com­ment on pay­ment struc­ture.

”We’ve learned first­hand there is no one-size-fits-all ap­proach to ac­cess and re­im­burse­ment for gene ther­a­py and are will­ing to try a num­ber of pay­ment struc­tures that re­spond to the unique needs and pri­or­i­ties of pa­tients, providers and pay­ers with­out cre­at­ing added bar­ri­ers or com­plex­i­ties,” she said.

She added that “sev­er­al” pa­tients had been dosed with Zyn­te­glo pri­or to its with­draw­al in Eu­rope and sev­er­al more who had al­ready con­sent­ed to treat­ment will still re­ceive it. Roll­out there was dis­rupt­ed by man­u­fac­tur­ing de­lays and an (ul­ti­mate­ly not born out) safe­ty scare; blue­bird said in quar­ter­ly fil­ings it be­gan re­ceiv­ing rev­enue from the drug but that the rev­enue was “im­ma­te­r­i­al.”

A US ap­proval would make Zyn­te­glo the third gene ther­a­py ap­proved in the US, af­ter Spark’s Lux­tur­na and No­var­tis’ Zol­gens­ma. It would be the first ap­proved ex-vi­vo gene ther­a­py, where cells are re­moved from a pa­tient, mod­i­fied and then re­in­fused — as op­posed to in vi­vo gene ther­a­pies, where a pa­tient’s cells are mod­i­fied di­rect­ly in their body.

Al­though not a uni­ver­sal cure, Zyn­te­glo has proven a high­ly ef­fec­tive treat­ment for be­ta-tha­lassemia, a dis­ease marked by month­ly blood trans­fu­sions that can be de­bil­i­tat­ing over time. Out of 36 evalu­able pa­tients in the com­pa­ny’s tri­als, 32 no longer need­ed trans­fu­sions for at least 12 months.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

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Usama Malik

Ex-Im­munomedics CFO charged with in­sid­er trad­ing, faces up to 20 years in prison af­ter al­leged­ly tip­ping off girl­friend and rel­a­tives of a PhI­II suc­cess

The former CFO of Immunomedics, who helped steer the company to its $21 billion buyout by Gilead last year, has been charged with insider trading, the Department of Justice announced Thursday.

Usama Malik tipped off his then-girlfriend and four others that a Phase III study for Trodelvy would be stopped early four days before Immunomedics publicly announced the result in April 2020, DoJ alleged in its complaint. The individuals then purchased Immunomedics shares, selling them after the news broke and Immunomedics’ stock price doubled.

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

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“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Biospec­i­men M&A: Dis­cov­ery ac­quires Al­bert Li's he­pa­to­cyte project; PhI­II tri­al on Bay­er's Nube­qa reached pri­ma­ry end­point

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While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Vas Narasimhan, Novartis CEO (Thibault Camus/Pool via AP Images)

With gener­ic com­pe­ti­tion heat­ing up, Vas Narasimhan out­lines No­var­tis' growth plans at R&D day

Thursday marks Novartis’ annual R&D day, and with it comes CEO Vas Narasimhan’s attempt to spotlight the company’s pipeline strategy and emerging stars.

The biggest question entering Thursday’s presentation dealt with how the big biopharma will make up revenues from upcoming generic competition — Novartis says within the next five years, generics will eat away roughly $9 billion in sales. To offset this, Narasimhan outlined a strategy for 4% growth or higher until 2026, focusing on six key medicines he believes will see multibillion dollar profits during this time.

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Astellas and Dyno will work together as part of an R&D pact to develop next-gen AAV vectors for gene therapy using Dyno’s CapsidMap platform directed at skeletal and cardiac muscle, the companies said Wednesday. Under the terms of the deal, Dyno will design AAV capsids for gene therapy, while Astellas will be responsible for conducting preclinical, clinical and commercialization activities for gene therapy product candidates using the capsids.

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