Cel­gene shak­en again af­ter the FDA kicks back their mar­ket­ing ap­pli­ca­tion on block­buster hope­ful ozan­i­mod

Cel­gene has been slammed with a refuse-to-file let­ter from the FDA for ozan­i­mod, the biggest late-stage drug it has in the pipeline.

The biotech re­port­ed af­ter the mar­ket closed Tues­day that the RTF came through be­cause the FDA de­ter­mined “that the non­clin­i­cal and clin­i­cal phar­ma­col­o­gy sec­tions in the NDA were in­suf­fi­cient to per­mit a com­plete re­view” for mul­ti­ple scle­ro­sis.

That’s go­ing to hurt — bad.

Cel­gene piv­ot­ed to ozan­i­mod as its pri­ma­ry Phase III block­buster hope­ful, ob­tained in their $7.2 bil­lion Re­cep­tos buy­out, af­ter its $710 mil­lion cash roll of the dice on the in­flam­ma­to­ry bow­el dis­ease drug mon­gersen (GED-301) came up snake eyes in Phase III last fall. Cel­gene has said ozan­i­mod is worth $4 bil­lion to $6 bil­lion a year in peak sales, but that’s be­com­ing an in­creas­ing­ly tough pitch with an­a­lysts.

An RTF is not the kiss of death for ozan­i­mod, but at the very least it de­lays any launch and forces CEO Mark Alles to ex­plain how they man­aged to fum­ble the ball again. For Cel­gene, it’s an un­ac­cus­tomed po­si­tion, rais­ing doubts about the com­pa­ny’s fu­ture. Notes Baird’s Bri­an Sko­r­ney:

With so many re­cent mis­steps and Revlim­id IP still a big risk amidst mul­ti­ple Para­graph IV chal­lenges, in­vestors are hes­i­tant to get back in­to what was once biotech’s poster child for con­tin­ued growth and sol­id ex­e­cu­tion.

Leerink’s Ge­of­frey Porges took a look and came up with some dis­com­fort­ing con­clu­sions about Cel­gene. His the­o­ry about what went wrong:

This on­ly adds to in­vestors’ grow­ing un­ease with the com­pa­ny’s di­rec­tion and over­sight of key ac­tiv­i­ties – in this case the com­pa­ny clear­ly made a de­ci­sion to file this ap­pli­ca­tion at risk, de­spite late in­for­ma­tion that might have been more thor­ough­ly dis­closed and ex­plored in the ap­pli­ca­tion, had the fil­ing been post­poned by a few months. The spe­cif­ic rea­sons for the RTF have not been com­plete­ly ex­plained, but Cel­gene’s com­ments sug­gest that a Cel­gene-con­duct­ed small PK/PD study for Ozan­i­mod that was com­plet­ed late last year and showed some anom­alies (ex­po­sure or PK vari­ances) which, when com­bined with the known safe­ty li­a­bil­i­ties of the S1P class, prob­a­bly trig­gered the FDA to re­quest more com­plete dis­clo­sure of this sup­ple­men­tal da­ta, and po­ten­tial­ly fur­ther ex­plo­ration of these vari­ances.

The biotech post­ed pos­i­tive Phase III da­ta on ozan­i­mod late in Oc­to­ber, in­clud­ing some fa­vor­able com­par­isons with Avonex. But there were some holes in the pre­sen­ta­tion. As not­ed last sum­mer, Cel­gene’s drug did not demon­strate a dis­abil­i­ty ben­e­fit over Avonex on a pooled ba­sis, which will like­ly blunt its com­mer­cial prospects. In­ves­ti­ga­tors re­cruit­ed 1,346 pa­tients for the SUN­BEAM tri­al, post­ing sta­tis­ti­cal­ly sig­nif­i­cant scores for the an­nu­al­ized re­lapse rate. But in a pooled analy­sis of SUN­BEAM and RA­DI­ANCE Part B stud­ies, their drug did not hit the goal for the time to 3-month con­firmed dis­abil­i­ty pro­gres­sion.

Jay Back­strom

The plan now is to get in front of the FDA AS­AP and see what they need to do to get this drug back in­to the sys­tem and hope­ful­ly point­ed to an ap­proval.

Cel­gene spooked the mar­ket re­cent­ly with some shaky fi­nan­cials, but man­aged to calm the wa­ters with its buy­out of Juno and the prospect of be­com­ing a leader in CAR-T ther­a­pies. Its set­back to­day will not sit well with in­vestors, who swift­ly drove down Cel­gene’s shares by 6.8%.

“We re­main con­fi­dent in ozan­i­mod’s clin­i­cal pro­file demon­strat­ed in the piv­otal pro­gram in re­laps­ing forms of mul­ti­ple scle­ro­sis,” said Jay Back­strom, the CMO and head of Glob­al Reg­u­la­to­ry Af­fairs for Cel­gene. “We will work with the FDA to ex­pe­di­tious­ly ad­dress all out­stand­ing items and bring this im­por­tant med­i­cine to pa­tients.”

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

A lab technician works during research on coronavirus at Johnson & Johnson subsidiary Janssen Pharmaceutical in Beerse, Belgium, Wednesday, June 17, 2020. (Virginia Mayo/AP Images)

End­points News ranks all 28 play­ers in the Covid-19 vac­cine race. Here's how it stacks up to­day

The 28 players now in or close to the clinical race to get a Covid-19 vaccine over the finish line are angling for a piece of a multibillion-dollar market. And being first — or among the leaders — will play a big role in determining just how big a piece.

Endpoints News writer Nicole DeFeudis has posted a snapshot of all the companies, universities and hospital-based groups now racing through the clinic, ranking them according to their place in the pipeline as well as the latest remarks available on timelines. And we’ll keep this lineup updated right through the end of the year, as the checkered flags start to fall, possibly as early as October.

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Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

Bayer's Marianne De Backer with Endpoints founder John Carroll, Endpoints@JPM20 (Jeff Rumans for Endpoints News)

UP­DAT­ED: Hunt­ing a block­buster, Bay­er forges an $875M-plus M&A deal to ac­quire women’s health biotech

Bayer has dropped $425 million in cash on its latest women’s health bet, bringing a UK biotech and its non-hormonal menopause treatment into the fold.

KaNDy Therapeutics had its roots in GlaxoSmithKline, which spun out several neuroscience drugs into NeRRe Therapeutics back in 2012. Five years later the team created a new biotech to focus solely on NT-814 — which they considered “one of the few true innovations in women’s health in more than two decades.”

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Eric Shaff (Seres)

UP­DAT­ED: Af­ter a 4-year so­journ, strug­gling mi­cro­bio­me pi­o­neer Seres claims a break­out PhI­II come­back. And shares re­spond in fren­zied spike

Almost exactly 4 years ago, Seres Therapeutics $MCRB experienced one of those soul-crunching failures that can raise big questions about a biotech’s future. Out front in their pursuit of a gut punch to C. difficile infection (CDI), the Phase II test was a flat failure, and investors wiped out a billion dollars of equity value that never returned in the years that followed.

Seres, though, pressed ahead, changing out CEOs a year ago — bidding Merck vet Roger Pomerantz farewell from the C suite — and pushing through a Phase III, hoping that amping up the dosage would make the key difference. And this morning, they unveiled a claim that they had aced the Phase III and positioned themselves for a run at a landmark FDA OK.

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Michel Vounatsos, Biogen CEO (via YouTube)

Bio­gen scores a pri­or­i­ty re­view for its Alzheimer's drug ad­u­canum­ab, mov­ing one gi­ant leap for­ward in its con­tro­ver­sial quest

Biogen scored a big win at the FDA today as regulators accepted their application for the controversial Alzheimer’s drug aducanumab and gave it a priority review.

The PDUFA date is March 7, 2021.

Significantly, Biogen says it did not use its priority review voucher to win special treatment at the FDA. The agency handed that out gratis.

That’s the ideal scenario Biogen was looking for as disappointed analysts wondered aloud about the delayed application earlier in the year.

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Robert Gould, Fulcrum Therapeutics CEO

Ful­crum stum­bles in PhII of old GSK drug, send­ing shares tum­bling

Investors are selling off shares of Fulcrum Therapeutics $FULC after their lead drug failed in a Phase II trial.

The company, founded three years ago on new research techniques such as CRISPR screening, isolated a gene called DUX4 they believed to have a central role in facioscapulohumeral muscular dystrophy, where patients’ muscle dies and is replaced by fat. And to target it, they licensed a GlaxoSmithKline drug that had failed as a cardio drug.

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Eisai moves to 200 Metro Blvd. by late 2021 (ON3)

Ei­sai is cre­at­ing a new US cor­po­rate, R&D HQ in Roche’s old Nut­ley, NJ cam­pus

Eight years after Roche pulled up stakes from Nutley, NJ in a major R&D reorganization, Japan’s Eisai is moving its US corporate and research hub into their old campus.

Now the ON3 property, Eisai — a longtime Biogen partner focused on neurodegenerative disorders like Alzheimer’s — will bring together a staff of up to 1,200 employees. And execs are pitching the move to the New Jersey campus as a cultural game-changer.

Lig­and scoops up Pfenex for up to $516M, adding pro­teins to their an­ti­body chick­ens and de­liv­ery tech

The technology hunting folks over at Ligand Pharmaceuticals have picked up a new one from across town, for a significant price.

Ligand has acquired fellow San Diego-based biotech Pfenex and their protein expression platform for $438 million cash, plus $78 million in contingent value agreements should an undisclosed milestone be hit before the end of next year.  The deal pays $12 per share, or $4.34 more than what Pfenex had been trading at before the announcement.