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.”

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

UP­DAT­ED: As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

BeiGene and Mus­tang nail down spe­cial FDA sta­tus for top drugs; Roche bags added cov­er­age for Hem­li­bra

→ BeiGene $BGNE is getting a boost in its drive to field a rival to Imbruvica. The FDA has offered an accelerated review to zanubrutinib, a BTK inhibitor that has posted positive results for mantle cell lymphoma. The PDUFA date lands on February 27, 2020. The drug scored breakthrough status at the beginning of the year.

→ BeiGene isn’t the only biopharma company to gain special regulatory status today. Mustang Bio $MBIO and St. Jude Children’s Research Hospital announced that MB-107, a lentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency, also known as bubble boy disease, has been granted Regenerative Medicine Advanced Therapy status.