No stranger to head­winds, blue­bird runs in­to two PDU­FA de­lays un­re­lat­ed to new safe­ty is­sues

Blue­bird bio hit an­oth­er speed bump Tues­day in its ef­forts to win its first FDA ap­provals as reg­u­la­tors pushed back two PDU­FA dates.

The FDA de­layed the ac­tion dates for beti-cel and eli-cel, the one-time gene ther­a­pies for be­ta-tha­lassemia and cere­bral adrenoleukody­s­tro­phy, by three months each, the biotech said in a press re­lease Tues­day morn­ing. Orig­i­nal­ly sched­uled for May and June, re­spec­tive­ly, the new PDU­FA dates were pushed back to Au­gust and Sep­tem­ber.

Ac­cord­ing to blue­bird, the de­lays are not the re­sult of any new safe­ty events, but rather “to al­low time to re­view ad­di­tion­al clin­i­cal in­for­ma­tion pre­vi­ous­ly sub­mit­ted by the com­pa­ny in re­sponse to FDA in­for­ma­tion re­quests as part of its on­go­ing re­views.” The com­pa­ny al­so said the de­lays won’t af­fect the pri­or­i­ty re­view sta­tus for ei­ther pro­gram or pre­vent it from earn­ing pri­or­i­ty re­view vouch­ers should ei­ther be green­light­ed.

Shares of blue­bird $BLUE fell a mod­est 4% as the mar­ket opened Tues­day.

An­a­lysts saw the lack of new safe­ty is­sues as a small win, giv­en how such con­cerns al­ways have the gene ther­a­py field on guard. Mani Foroohar of SVB Leerink wrote to in­vestors Tues­day morn­ing safe­ty con­tin­ues to be “a crit­i­cal is­sue — as BLUE looks to ex­tend its cash run­way with sale of pri­or­i­ty re­view vouch­ers up­on BLA ap­provals.”

Foroohar added that much re­mains up in the air, as blue­bird is plan­ning to give fur­ther up­dates in its full-year re­port next month. Ad­di­tion­al­ly, the FDA had planned to hold an ad­comm for beti-cel in March, where the full breadth of any safe­ty is­sues will like­ly be dis­cussed in de­tail. The ad­comm will still take place but will al­so be de­layed to align with the new PDU­FA dates, and a new date has not been set.

What­ev­er the rea­son for Tues­day’s news, the de­lays mark yet an­oth­er po­ten­tial road­block in blue­bird’s long-run­ning quest to get its gene ther­a­pies ap­proved in the US.

Last Feb­ru­ary, blue­bird vol­un­tar­i­ly paused two stud­ies for its sick­le cell gene ther­a­py af­ter two pa­tients un­ex­pect­ed­ly de­vel­oped can­cer and a can­cer-like case, re­sult­ing in a four-month clin­i­cal hold. Blue­bird lat­er demon­strat­ed that the can­cer case was un­re­lat­ed to the virus­es used in its gene ther­a­py and that the can­cer-like case was a mis­di­ag­no­sis. But the pause re­sult­ed in a de­layed launch for beti-cel, which us­es the same lentivi­ral de­liv­ery method, in Eu­rope.

Then, in Au­gust, an­oth­er can­cer-like case popped up in a tri­al for eli-cel, forc­ing blue­bird to hit the brakes on the study. That case, blue­bird said, did ap­pear linked to the gene ther­a­py. In the same an­nounce­ment, blue­bird said it would stop sell­ing its gene ther­a­pies in Eu­rope af­ter fail­ing to reach pric­ing agree­ments with gov­ern­ments.

Ob­servers spec­u­lat­ed blue­bird did not want to charge less for the drug, brand­ed Zyn­te­glo in Eu­rope, for fear it would ul­ti­mate­ly have to low­er prices in the US. 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 was still work­ing af­ter five years. But blue­bird want­ed some­thing in the range of $1.8 mil­lion af­ter that time pe­ri­od.

The biotech in­stead shift­ed its fo­cus to a US ap­proval and com­plet­ed its split in­to two com­pa­nies, os­ten­si­bly dri­ven by the re­peat­ed de­lays in its gene ther­a­py pro­grams. Blue­bird sub­mit­ted its ap­pli­ca­tion late last year and was grant­ed pri­or­i­ty re­view in No­vem­ber for beti-cel and De­cem­ber for eli-cel.

Should blue­bird win ap­proval for one of the pro­grams, it would be­come the third gene ther­a­py to en­ter the US mar­ket af­ter Spark’s Lux­tur­na and No­var­tis’ Zol­gens­ma and the first-ever FDA ap­proved ex vi­vo gene ther­a­py.

Clar­i­fi­ca­tion: This ar­ti­cle has been up­dat­ed to clar­i­fy the tim­ing of the sched­uled ad­comm for beti-cel. Pre­vi­ous­ly slat­ed for March, the ad­comm will be de­layed and does not have a new date set as of Tues­day, Jan. 18.  

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

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Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

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See­los Ther­a­peu­tics 'tem­porar­i­ly' stops study in rare neu­ro dis­or­der for busi­ness rea­sons

Microcap biotech Seelos Therapeutics is halting enrollment of its study in spinocerebellar ataxia type 3 (also known as Machado-Joseph disease) because of “financial considerations,” and in order to focus on other studies, the company said today, adding that the pause would be temporary.

The study will continue with the patients who have already enrolled, and the data from them will be used to decide whether to continue enrolling others in the future.

Alec­tor cuts 11% of work­force as it dou­bles down on late-stage neu­ro pro­grams part­nered with GSK, Ab­b­Vie

A month after revealing plans to concentrate on its late-stage immuno-neurology pipeline, Alector is trimming its headcount by 11%.

The layoffs will impact around 30 employees across the organization, the company disclosed in an SEC filing, adding that the plan will “better align the company’s resources” with the new strategy. With $712.9 million in cash, cash equivalents and investments as of the end of 2022, Alector believes the reserves will now get it through 2025.

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Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

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Hugo Peris, Spiral Therapeutics CEO

Hear­ing-fo­cused biotech grabs trio of pro­grams from Oton­o­my's fire sale

Otonomy may be shutting down, but the lessons learned there will live on at another biotech working on new treatments for hearing loss.

San Francisco-based Spiral Therapeutics has bought certain assets related to three of Otonomy’s programs, ranging from data, patent rights, and know-how to inventory. That includes data around Otonomy’s twice-failed lead program, OTO-104 (Otividex), a sustained-exposure formulation of dexamethasone.

FDA ap­proves Nar­can opi­oid over­dose re­ver­sal spray for over-the-counter sale

The FDA today approved Emergent BioSolutions’ Narcan brand naloxone nasal spray for over-the-counter sales. The nod was expected and comes on the heels of a unanimous 19-0 advisory committee vote in favor of approval last month.

The move to OTC means the opioid overdose reversal agent will now be available on grocery, convenience and gas stations shelves, as well as potentially for purchase online.

J&J bows out of RSV vac­cine race, end­ing PhI­II study and ced­ing to Pfiz­er, GSK

Johnson & Johnson announced Wednesday morning it is ending development of its adult RSV vaccine that was in the middle of a 27,200-patient trial, giving up a big slice of what’s expected to be the next multibillion-dollar pharma market.

The decision came down to the shifting RSV “competitive landscape,” a company spokesperson tells Endpoints News, adding the “breadth of options” was much different than when J&J first started its pivotal study. The spokesperson declined to comment on the Phase III data, saying only the shot is undergoing an “ongoing assessment.”

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No longer ‘dead or just hi­ber­nat­ing,’ drug­mak­ers re­turn to heart med­i­cines

In 2015, now-FDA Commissioner Robert Califf joined industry, academic and regulatory representatives in Washington to discuss why more drugs weren’t in development for cardiovascular diseases, the leading US cause of death and once a mainstay of pharmaceutical industry blockbusters.

The group pointed to many reasons. Clinical trials could take years and testing was expensive. Wide availability of generic drugs made the commercial prospects uncertain. Their paper title summed up the mood: “Cardiovascular Drug Development: Is it Dead or Just Hibernating?”

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