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.”

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Aduhelm OK 'bit­ter­sweet' for ALS ad­vo­cates; Con­trast­ing Covid-19 vac­cine read­outs; GSK joins TIG­IT bat­tle; 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.

With the busiest days of June now behind us, we’re starting to think seriously about the second half of the year. In August, we have scheduled a special report where Endpoints will compile a list of the 20 most influential R&D executives in biopharma. Know a luminary who should definitely be included? Nominate them now.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,800+ biopharma pros reading Endpoints daily — and it's free.

Who are the lu­mi­nar­ies dri­ving the biggest ad­vances in bio­phar­ma R&D? End­points News is ask­ing for your nom­i­na­tions for a spe­cial re­port

In biopharma, driving a drug to market is the ultimate goal — but none of that happens without a strong research and development program. At the most successful companies, those R&D efforts are spearheaded by true innovators in the field who are always looking for that next novel mechanism of action or breakthrough safety profile.

Now, Endpoints News is asking you to tell us who those guiding lights are.

Leen Kawas, Athira CEO

Biotech founder placed on leave as $400M Alzheimer's start­up idea comes un­der scruti­ny

Athira Pharma, the Alzheimer’s biotech that emerged out of obscurity last year and raised nearly $400 million for a dark-horse approach to treating neurodegeneration, has found itself in sudden turmoil.

On Tuesday evening, the company released a terse statement announcing that CEO and founder Leen Kawas had been placed on administrative leave while an independent review board investigated “actions stemming” from her doctoral research at Washington State University. Mark Litton, who joined the company as COO two years ago, will take over day-to-day operations, they said.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,800+ biopharma pros reading Endpoints daily — and it's free.

Bris­tol My­ers breaks the bank on Ei­sai's fo­late re­cep­tor ADC drug, lay­ing out more than $3B+ for rights

For years, innovation in oncology has been a crapshoot with Big Pharma — the whales at the table — dropping the big bucks for the key to the next generation of tumor fighters. Bristol Myers Squibb hasn’t exactly made a name for being an innovator in the space, but that doesn’t mean it won’t splash in when it sees a potential winner.

Now, with a massive check in hand, the drugmaker is willing to put its intuition to the test.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,800+ biopharma pros reading Endpoints daily — and it's free.

Michael Chambers (L) and John Ballantyne

Dana­her strikes deal to buy boom­ing next-gen man­u­fac­tur­er Alde­vron for $9.6B

Life sciences conglomerate Danaher Corp. $DHR has struck a deal to buy the fast-growing Aldevron, one of the world’s top manufacturers of hotly sought-after plasmid DNA, mRNA and recombinant proteins for the burgeoning world of vaccine and drugmakers pushing some game-changing technologies.

Buyout talks set the stage for Danaher to settle on a $9.6 billion cash pact to acquire the private Fargo, ND-based company — a key supplier for a disruptive new Covid vaccine as well as a host of gene and cell therapy and CRISPR gene editing players — founded by Michael Chambers and CSO John Ballantyne as a crew of 2 back in 1998.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Jeff Albers, Blueprint CEO

Blue­print Med­i­cines nabs 4th ap­proval in bid to­ward prof­itabil­i­ty

Blueprint Medicines’ push to profitability continues.

On Wednesday, the Cambridge biotech announced the FDA approved its longtime lead drug, Ayvakit, for advanced systemic mastocytosis, a group of debilitating rare diseases where one type of immune cell — mast cells — builds up uncontrollably in a particular organ. The decision came on the heels of Phase III trials showing that more than half of late-stage patients who received the drug responded to it and did so for just over three years.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,800+ biopharma pros reading Endpoints daily — and it's free.

Franz-Werner Haas, CureVac CEO (Christoph Schmidt/picture-alliance/dpa/AP Images)

UP­DAT­ED: Cure­Vac blames vari­ants as a close­ly-watched Covid vac­cine goes down in flames, fail­ing piv­otal study with woe­ful da­ta

CureVac was widely expected to come in with a late but likely late-stage winner in the race to develop new vaccines for the Covid-19 pandemic. Instead, late Wednesday, the German biotech said their mRNA candidate CVnCoV flat failed a pivotal trial — quashing any hopes for a quick entry in the blockbuster field and gutting their share price.

CVnCoV demonstrated an interim vaccine efficacy of 47% against COVID-19 disease of any severity and did not meet prespecified statistical success criteria. Initial analyses suggest age and strain dependent efficacy.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,800+ biopharma pros reading Endpoints daily — and it's free.

Al Sandrock, Biogen R&D chief (Biogen via YouTube)

Days af­ter con­tro­ver­sy greet­ed Bio­gen's block­buster Alzheimer's OK, the big biotech con­cedes a set­back on the tau front

Just days after triggering a maelstrom of controversy with their decision to launch an unproven Alzheimer’s drug with a $56,000 price, Biogen $BIIB is back with the latest data on its mid-stage tau drug.

And it’s not good.

The big biotech says that gosuranemab — targeted at tau, the second leading drug target in Alzheimer’s — flat failed its Phase II and will now be taken out and dumped in the mass grave for all but one other Alzheimer’s drug in the past generation.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,800+ biopharma pros reading Endpoints daily — and it's free.