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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Roche's Tecen­triq cross­es the fin­ish line first in ad­ju­vant lung can­cer, po­ten­tial­ly kick­ing off gold rush

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

FDA's vac­cine ad­comm unan­i­mous­ly sup­ports Mod­er­na's boost­er in same pop­u­la­tions as Pfiz­er's boost­er

The FDA’s vaccine advisory committee on Thursday voted 19-0 in support of expanding Moderna’s Covid-19 vaccine EUA for booster doses for certain high-risk individuals. FDA is expected to authorize the Moderna booster shortly.

Similarly to the Pfizer booster shot, Moderna’s will likely be authorized for those older than 65, adults at high risk of severe Covid-19, and adults whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of Covid-19. But unlike the Pfizer adcomm, where FDA had to scramble to get the committee to vote in favor of a booster, this committee was unanimous with the Moderna shot.

FDA ad­comm votes unan­i­mous­ly in sup­port of a J&J Covid-19 boost­er two months af­ter one-dose shot

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Friday voted 19-0 in favor of authorizing a second shot of J&J’s Covid-19 vaccine to follow at least two months after the initial dose.

Regulators don’t have to follow VRBPAC’s recommendation, but they almost always do. Considering that the CDC’s advisory committee has already been set to review the expanded EUA, VRBPAC’s recommendation is likely to be adopted.

Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'

 

Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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In­cyte yanks EU ap­pli­ca­tion for PD-1 drug, cit­ing in­abil­i­ty to an­swer reg­u­la­tors' 'ma­jor con­cern­s'

Hoping to wedge its way into a crowded PD-(L)1 field, Incyte faced a huge setback when the FDA sent back its application for an initial indication earlier this year. Now, the drugmaker is giving up hope in Europe as well.

Incyte has withdrawn its EU application for PD-1 drug Zynyz, or retifanlimab, after saying it couldn’t adequately address the CHMP’s questions over survival data underpinning its market hopes in squamous cell carcinoma of the anal cavity, the EMA revealed.

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