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.

Bio­mark­er 'roadmap­s' and the fu­ture of can­cer R&D; Cur­tain rais­es on #AS­CO22; Pfiz­er, No­var­tis tack­le drug ac­cess; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

While this was not a week for earth-shattering news, there were certainly a lot of interesting tidbits. If you found this recap helpful, please recommend it to your friends and colleagues. We’ll see you on the other side of the long weekend.

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Keep­ing pres­sure on Am­gen, Mi­rati draws mixed re­views on lat­est cut of KRAS da­ta

As the close runner-up to Amgen’s Lumakras in the KRAS race, any data cut from Mirati’s adagrasib continues to draw scrutiny from analysts. And the latest batch of numbers from ASCO is a decidedly mixed bag.

While a quick comparison suggests that adagrasib spurred slightly more responses and led to a longer overall survival than Lumakras among a group of non-small cell lung cancer patients, its duration of response appears shorter and the safety profile continues to spark concern.

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Tran­si­tion to new Eu­ro­pean clin­i­cal tri­als in­fo sys­tem starts slow­ly

At the end of January, the European Medicines Agency officially launched its new clinical trials info system (CTIS), although the migration to the new platform has only really just begun, and sponsors have until the end of January 2023 before all initial trial applications must be submitted through CTIS.

Overall, 56 clinical trial applications have been submitted in CTIS during the first 3 months since the launch of the system on Jan. 31, according to new data posted by the EMA. By comparison, about 4,000 new trials are authorized each year across Europe.

Ann is one of ViiV Healthcare's newest spokespeople as the retired school administrator speaks up about her HIV status.

GSK's Vi­iV de­buts next evo­lu­tion in HIV med Dova­to cam­paign with new spokes­peo­ple and new mes­sage

When Ann saw the first TV commercials for HIV medicine Dovato, she didn’t see herself represented. So the 74-year-old retired school administrator who’s been living with HIV since 1998, reached out to GSK’s ViiV Healthcare and asked why not?

Now Ann is one of three people starring in ViiV’s latest Dovato campaign called “Detect This.” The next-step evolution in the branded campaign plays on the word “detect” — often used in describing HIV status under control as undetectable — but in this case, uses the word as a directive for people to understand they can use fewer medicines.

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Switzer­land to de­stroy over 600,000 ex­pired dos­es of Mod­er­na Covid vac­cine

As concerns related to uptake and distribution continue to linger, Switzerland is among the first countries that plans to destroy hundreds of thousands of expired and unused Covid-19 vaccine doses.

The European country said it plans to destroy more than 600,000 doses of Moderna’s Spikevax Covid-19 vaccine as the doses have reached their expiration date.

However, Moderna CEO Stéphane Bancel told the World Economic Forum in Davos, Switzerland that he’s in the process of throwing 30 million doses in the garbage, exclaiming, “We have a big demand problem.”

AS­CO ab­stracts mint some ear­ly win­ners, but Io­vance, Spring­Works get hit by mas­sive loss­es

Before cancer-focused biotechs start their trek to the first in-person American Society of Clinical Oncology (ASCO) annual conference since the pandemic began, investors have taken a good look at the teasers for the data scheduled to be presented — and started placing bets.

With its power to confer overnight fame, ASCO is a stage where impressive or surprise debut performances can go a long way. On the other hand, disappointing details could be punishing.

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Nassim Usman, Catalyst Biosciences CEO

Af­ter $60M Ver­tex deal, group of Cat­a­lyst share­hold­ers claims biotech could’ve sold as­sets three years ago

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In came Vertex, with $60 million to buy up the South San Francisco biotech’s preclinical complement drugs, which target the system that bridges the body’s innate and adaptive immune response and a class most known for Ultomiris and Soliris. The deal includes CB 2782-PEG, the dry AMD drug that Biogen no longer wanted in March.

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Levi Garraway, Roche CMO (Genentech)

Roche's CD20xCD3 does­n't beat Gen­mab at ORR, but sets bar for CR da­ta on lym­phoma drug

On its way to potentially becoming the first to market with a CD20xCD3 bispecific for aggressive lymphoma, Big Pharma’s largest R&D spender has some more data to pad its case with an FDA filing slated for later this year.

Roche dropped some more details from a Phase II expansion study of its fixed-duration glofitamab, to be presented at next week’s ASCO annual meeting, in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The patients had received a median of three prior therapies.

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Lina Khan, FTC chair (Graeme Jennings/Pool via AP Images)

Pile-on over PBMs con­tin­ues with FTC com­ments and a new bi­par­ti­san Sen­ate bill

More than 500 stakeholders sent comments to the FTC on whether the commission should look further into pharma middlemen, known as PBMs, with many of the commenters calling for more federal oversight.

Similar to the critical open comment period in a deadlocked FTC session last February, pharmacies and pharmacy groups are continuing to call out the lack of transparency among the top 3 PBMs, which control about 80% of the market.