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.”

Patrik Jonsson, the president of Lilly Bio-Medicines

Who knew? Der­mi­ra’s board kept watch as its stock price tracked Eli Lil­ly’s se­cret bid­ding on a $1.1B buy­out

In just 8 days, from December 6 to December 14, the stock jumped from $7.88 to $12.70 — just under the initial $13 bid. There was no hard news about the company that would explain a rise like that tracking closely to the bid offer, raising the obvious question of whether insider info has leaked out to traders.

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2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Aymeric Le Chatelier, Ipsen

A $1B-plus drug stum­bles in­to an­oth­er big PhI­II set­back -- this time flunk­ing fu­til­i­ty test -- as FDA hold re­mains in ef­fect for Ipsen

David Meek

At the time Ipsen stepped up last year with more than a billion dollars in cash to buy Clementia and a late-stage program for a rare bone disease that afflicts children, then CEO David Meek was confident that he had put the French biotech on a short path to a mid-2020 launch.

Instead of prepping a launch, though, the company was hit with a hold on the FDA’s concerns that a therapy designed to prevent overgrowth of bone for cases of fibrodysplasia ossificans progressiva might actually stunt children’s growth. So they ordered a halt to any treatments for kids 14 and under. Meek left soon after to run a startup in Boston. And today the Paris-based biotech is grappling with the independent monitoring committee’s decision that their Phase III had failed a futility test.

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FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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Gilead claims Tru­va­da patents in HHS’ com­plaint are in­valid

Back in November, the Department of Health and Human Services took the rare step of filing a complaint against Gilead for infringing on government-owned patents related to the HIV drug Truvada (emtricitabine/tenofovir disoproxil fumarate) for pre-exposure prophylaxis (PrEP).

But on Thursday, Gilead filed its own retort, making clear that it does not believe it has infringed on the Centers for Disease Control and Prevention’s (CDC) Truvada patents because they are invalid.

Roche's check­point play­er Tecen­triq flops in an­oth­er blad­der can­cer sub­set

Just weeks after Merck’s star checkpoint inhibitor Keytruda secured FDA approval for a subset of bladder cancer patients, Swiss competitor Roche’s Tecentriq has failed in a pivotal bladder cancer study.

The 809-patient trial — IMvigor010 — tested the PD-L1 drug in patients with muscle-invasive urothelial cancer (MIUC) who had undergone surgery, and were at high risk for recurrence.

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Stephen Hahn, AP

The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

A few weeks ago, when Stephen Hahn was being lightly queried by Senators in his confirmation hearing as the new commissioner of the FDA, he made the usual vow to maintain the gold standard in drug development.

Neatly summarized, that standard requires the agency to sign off on clinical data — usually from two, well-controlled human studies — that prove a drug’s benefit outweighs any risks.

Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

That confirmatory trial the FDA demands can wait a few years. And most everyone in biopharma would tell you that’s the right thing for patients. They know its a tonic for everyone in the industry faced with pushing a drug through clinical development. And it’s helped inspire a global biotech boom.

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UP­DAT­ED: New play­ers are jump­ing in­to the scram­ble to de­vel­op a vac­cine as pan­dem­ic pan­ic spreads fast

When the CNN news crew in Wuhan caught wind of the Chinese government’s plan to quarantine the city of 11 million people, they made a run for one of the last trains out — their Atlanta colleagues urging them on. On the way to the train station, they were forced to skirt the local seafood market, where the coronavirus at the heart of a brewing outbreak may have taken root.

And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

The early reaction in the biotech industry has been classic, with small-cap companies scrambling to headline efforts to step in fast. But there are also new players in the field with new tech that has been introduced since the last of a series of pandemic panics that could change the usual storylines. And they’re volunteering for a crash course in speeding up vaccine development — a field where overnight solutions have been impossible to prove.

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