One of Kite Phar­ma’s CAR-T pa­tients died from cere­bral ede­ma, trig­ger­ing a safe­ty alarm

Kite Phar­ma re­vealed to­day that one of the pa­tients in their late-stage pro­gram for the CAR-T drug KTE-C19 died from cere­bral ede­ma, the same brain swelling con­di­tion that went on to scut­tle Juno Ther­a­peu­tics’ lead drug.

In a call with an­a­lysts for their Q1 re­port, the close­ly-watched biotech $KITE said that they had in­formed the FDA and there was no pause or halt to the study. The death in late April, though, clear­ly raised a red flag for an­a­lysts af­ter Kite had man­aged to get all the way through a piv­otal pro­gram with­out a death due to cere­bral ede­ma af­ter treat­ing hun­dreds of pa­tients.

David Chang, Kite

“It took about two days of pro­gres­sive­ly wors­en­ing neu­ro­log­i­cal events,” com­ment­ed Kite CMO David Chang. “In this time the pa­tient’s over­all con­di­tion was de­te­ri­o­rat­ing.”

“This pa­tient had re­frac­to­ry non-Hodgkin lym­phoma,” added Chang. “At the time of en­roll­ment he had ex­plo­sive dis­ease that was rapid­ly pro­gress­ing and had a lot of symp­toms from the tu­mor.” There was fever, con­cerns about un­der­ly­ing in­fec­tions – though tests came back neg­a­tive — and “pret­ty rapid­ly pro­gress­ing dis­ease.”

In an email, a spokesper­son for Kite not­ed that “we don’t see any safe­ty con­cerns. All axi-cel and KTE-C19 de­vel­op­ment stud­ies con­tin­ue as planned. As a re­minder, over­all in­ci­dence of KTE-C19 re­lat­ed grade 5 events stands at 2% in ap­prox­i­mate 200 pa­tients treat­ed in our study sup­ports the ben­e­fit of axi-cel and KTE-C19.  If pa­tients treat­ed in the NCI stud­ies are in­clud­ed, over 300 pa­tients have been treat­ed with KTE-C19.”

Kite’s shares dropped 10% as news of the death spread.

Kite had want­ed to fo­cus to­day pri­mar­i­ly on its com­mer­cial­iza­tion plans for this drug, look­ing to a pos­si­ble FDA ap­proval lat­er in the year. But af­ter Juno was forced to shelve JCAR015 af­ter it killed 5 pa­tients who suf­fered cere­bral ede­ma, the news clear­ly cap­tured an­a­lysts’ at­ten­tion.

The FDA quick­ly lift­ed their first clin­i­cal hold on Juno’s drug af­ter the first three deaths, in­di­cat­ing reg­u­la­tors’ al­lowance for the ad­vanced state most of these can­cer pa­tients are in when they get in­to a CAR-T study. When two more pa­tients died soon af­ter the hold was lift­ed, though, that ex­pe­ri­ence could raise ques­tions of whether reg­u­la­tors may have be­come more sen­si­tive to the safe­ty is­sues in­volved with these drugs.

Juno had ini­tial­ly blamed the first group of deaths on the use of flu­dara­bine dur­ing the pre­con­di­tion­ing reg­i­men pa­tients go through to make them more re­cep­tive to cell ther­a­py. So they dropped it, then saw more pa­tients die. The flu/cy com­bo, though, was used by Kite and oth­ers. Kite be­lieves it has just the right mix to gain ef­fi­ca­cy with­out cre­at­ing un­rea­son­able safe­ty is­sues.

These drugs — reengi­neered T cells tak­en from pa­tients and then re­in­fused — have had safe­ty is­sues from the very be­gin­ning, with a num­ber of pa­tients suf­fer­ing from cy­tokine storms that oc­ca­sion­al­ly turned lethal.

Chang said that they would con­tin­ue to con­sid­er the ef­fi­ca­cy and safe­ty of the drug as more stud­ies pro­ceed.

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.

Endpoints News

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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.

Tri­fec­ta of sick­le cell dis­ease ther­a­pies ex­tend life ex­pectan­cy, but are not cost-ef­fec­tive — ICER

Different therapeutic traits brandished by the three approved therapies for sickle cell disease all extend life expectancy, but their impact on quality of life is uncertain and their long-term cost-effectiveness is not up to scratch according to the thresholds considered reasonable by ICER, the non-profit concluded in a draft guidance report on Thursday.

Sickle cell disease (SCD), which encompasses a group of inherited red blood cell disorders that typically afflict those of African ancestry, impacts hemoglobin — and is characterized by episodes of searing pain as well as organ damage.