Samit Hirawat. Bristol-Myers Squibb

Bris­tol-My­ers is mak­ing a bee-line to the FDA with pos­i­tive liso-cel da­ta — but is it too late in the CAR-T game?

Bris­tol-My­ers Squibb came to ASH this past week­end with a va­ri­ety of mes­sages on the new can­cer drugs they had ac­quired in the big Cel­gene buy­out, in­clud­ing liso-cel, the lead CAR-T pro­gram picked up in the $9 bil­lion Juno ac­qui­si­tion. And one of the most im­por­tant was that they had the piv­otal ef­fi­ca­cy and safe­ty da­ta need­ed to snag an ap­proval from the FDA next year, with the BLA on track for a fil­ing this month.

Pro­vid­ed there are no sna­fus or even mod­est stum­bles now, they should get an OK with­in the 2020 time­line lined out in their $9 CVR for Cel­gene — the first in a tri­fec­ta of ap­provals re­quired for a pay­out.

Whether they can go on to make it in­to a vi­able com­mer­cial ther­a­py, though, is a whole oth­er thing.

At first glance, there isn’t any­thing about the safe­ty and ef­fi­ca­cy da­ta that would force a CRL or de­lay. In a large tri­al of pa­tients with re­lapsed/re­frac­to­ry large B-cell lym­phomas in­ves­ti­ga­tors tracked an out­stand­ing 73% re­sponse rate and 53% com­plete re­sponse rate in heav­i­ly pre­treat­ed pa­tients with few op­tions.

That’s in line with Yescar­ta from Gilead’s Kite, which snagged an ap­proval more than 2 years ago, just af­ter No­var­tis’ Kym­ri­ah came through.

Then there’s safe­ty. To be sure, the drug has safe­ty is­sues. There were 4 pa­tients in the study who died af­ter treat­ment. Sev­er­al oth­ers died for un­re­lat­ed is­sues. But…with on­ly a 2% rate of cy­tokine re­lease syn­drome, Bris­tol-My­ers has a shot at a dif­fer­en­ti­at­ed safe­ty pro­file.

“There is a po­ten­tial these pa­tients can be treat­ed on an out­pa­tient ba­sis,” says Samit Hi­rawat, the chief med­ical of­fi­cer at Bris­tol-My­ers. He not­ed that 26% of pa­tients were nev­er ad­mit­ted, while 76% were ad­mit­ted 4 days or lat­er af­ter ther­a­py. The key is to treat them at a hos­pi­tal with the in­fra­struc­ture to pro­vide care 24/7, so a pa­tient can be ad­mit­ted at any time lat­er if need­ed.

How that will fly with pay­ers af­ter ri­vals have been on the mar­ket for about 3 years, with new ev­i­dence that ear­li­er use of steroids can dra­mat­i­cal­ly re­duce CRS and con­sid­er­able dura­bil­i­ty of re­sponse, will have to be seen.

But time is not on Bris­tol-My­ers’ side. Liso-cel is the long de­layed fol­lowup to the dis­as­trous JCAR015, which killed a num­ber of pa­tients. Their set­back threw them years off sched­ule. And ri­vals are ad­vanc­ing off-the-shelf al­ter­na­tives or oth­er new ap­proach­es that could knock the pi­o­neers com­plete­ly out of the game. In the mean­time, Bris­tol-My­ers is gath­er­ing its own dura­bil­i­ty da­ta and will grad­u­al­ly see if their mix of CD4 and CD8 cells can do bet­ter.

The main in­ter­est now is in the time­line around the ap­proval. Hi­rawat says they’ll ask for pri­or­i­ty re­view, and there’s every rea­son to be­lieve that reg­u­la­tors will move swift­ly — bar­ring a nasty sur­prise.

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.

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.

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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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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UP­DAT­ED: Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

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UP­DAT­ED: 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 dusts off a failed Ebo­la drug as coro­n­avirus spreads; Ex­elix­is boasts pos­i­tive Ph I/II da­ta

→ Less than a year ago Gilead’s antiviral remdesivir failed to make the cut as investigators considered a raft of potential drugs that could be used against an Ebola outbreak. But it may gain a new mission with the outbreak of the coronavirus in China, which is popping up now around the world.

Gilead put out a statement saying that they’re now in discussions with health officials in the US and China about testing their NUC against the virus. It’s the latest in a growing lineup of biopharma companies that are marshaling R&D forces to see if they can come up with a vaccine or therapy to blunt the spread of the virus, which has now sickened hundreds, killed at least 17 people and led the Chinese government to start quarantining cities.

Alex Karnal (Deerfield)

Deer­field vaults to the top of cell and gene ther­a­py CD­MO game with $1.1B fa­cil­i­ty at Philadel­phi­a's newest bio­phar­ma hub

Back at the beginning of 2015, Deerfield Management co-led a $10 million Series C for a private gene therapy startup, reshaping the company and bringing in new leaders to pave way for an IPO just a year later.

Fast forward four more years and the startup, AveXis, is now a subsidiary of Novartis marketing the second-ever gene therapy to be approved in the US.

For its part, Deerfield has also grown more comfortable and ambitious about the nascent field. And the investment firm is now putting down its biggest bet yet: a $1.1 billion contract development and manufacturing facility to produce everything one needs for cell and gene therapy — faster and better than how it’s currently done.