Months af­ter an­oth­er lethal set­back, Juno fi­nal­ly opts to kill lead CAR-T

Juno CEO Hans Bish­op

Months af­ter one of the worst set­backs in the re­cent his­to­ry of drug de­vel­op­ment left a string of pa­tients dead, Juno has fi­nal­ly de­cid­ed that it will ter­mi­nate its lead drug pro­gram, hop­ing for a bet­ter out­come with an­oth­er CAR-T ther­a­py in its pipeline.

Juno CEO Hans Bish­op claimed $JUNO that its de­ci­sion to shelve JCAR015 was all due to the “un­ex­pect­ed” tox­i­c­i­ty that it dis­cov­ered af­ter the drug killed five pa­tients due to cere­bral ede­ma, or brain swelling. The sec­ond tal­ly of deaths, though, oc­curred in No­vem­ber, af­ter the com­pa­ny con­vinced the FDA to swift­ly lift a clin­i­cal hold on the drug by mak­ing the du­bi­ous claim that elim­i­nat­ing flu­dara­bine from the pre­con­di­tion­ing reg­i­men for pa­tients would re­solve the safe­ty is­sue that had al­ready killed sev­er­al late-stage can­cer pa­tients.

Flu­dara­bine is still com­mon­ly used in most CAR-T stud­ies, need­ed to help these cell ther­a­pies take ef­fect in pa­tients. This first wave of drugs ex­tracts T cells from pa­tients and then reengi­neers them to go af­ter can­cer cells, and progress has been reg­u­lar­ly marred by se­ri­ous safe­ty is­sues. But there’s still been no clear ex­pla­na­tion of why JCAR015 de­railed.

Shares of Juno dropped 8% Wednes­day evening on the biotech’s re­minder of its se­ri­ous­ly flawed ef­forts.

“We con­tin­ue to ex­pe­ri­ence en­cour­ag­ing signs of clin­i­cal ben­e­fit in our tri­al ad­dress­ing NHL, but we al­so rec­og­nize the un­for­tu­nate and un­ex­pect­ed tox­i­c­i­ty we saw in our tri­al ad­dress­ing ALL with JCAR015,” said Bish­op in a state­ment. “We have de­cid­ed not to move for­ward with the ROCK­ET tri­al or JCAR015 at this time, even though it gen­er­at­ed im­por­tant learn­ings for us and the im­munother­a­py field.”

Juno threw out sev­er­al vague fac­tors that may have trig­gered the deaths. But they all added up to a re­turn to Phase I to prove their point. And there was no time to go back to the draw­ing board. From the state­ment:

Through the in­ves­ti­ga­tion Juno iden­ti­fied mul­ti­ple fac­tors that may have con­tributed to this in­creased risk, in­clud­ing pa­tient spe­cif­ic fac­tors, the con­di­tion­ing chemother­a­py pa­tients re­ceived, and fac­tors re­lat­ed to the prod­uct. Al­though Juno be­lieves there are pro­to­col mod­i­fi­ca­tions and process im­prove­ments that could en­able Juno to pro­ceed with JCAR015 in clin­i­cal test­ing in adult r/r ALL, Juno would first need to es­tab­lish pre­lim­i­nary safe­ty and dose in a Phase I tri­al. As a re­sult of the tim­ing de­lay that would en­tail and Juno’s be­lief that it has oth­er prod­uct can­di­dates in its pipeline that are like­ly to pro­vide im­proved ef­fi­ca­cy and tol­er­a­bil­i­ty,

As just about every­one who fol­lows this field has ex­pect­ed for some time now, Juno is turn­ing to JCAR017, hop­ing to get back on track af­ter falling far be­hind the two lead­ers in the field: Kite and No­var­tis. In its state­ment to­day, Juno out­lined plans to launch a piv­otal study for r/r dif­fuse large B cell lym­phoma lat­er this year. The biotech, though, has now fall­en be­hind ri­vals by more than a year.

At one point Juno was con­sid­ered a con­tender for a pi­o­neer­ing ap­proval, run­ning neck-and-neck with Kite. Yes­ter­day, though, Kite post­ed im­pres­sive 6-month re­sults for its CAR-T ahead of its ap­pli­ca­tion for ap­proval, as Juno was just get­ting ready to for­mal­ly ter­mi­nate its trou­bled lead pro­gram.

Added Bish­op:

Look­ing for­ward in­to 2017, we con­tin­ue to be op­ti­mistic about the progress we are mak­ing with JCAR017 and our pipeline more broad­ly. We ex­pect 2017 will be a da­ta-rich year of key in­sights, based on up to 20 on­go­ing tri­als by year end, and we plan to present da­ta from these tri­als as ap­pro­pri­ate through­out the year.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Alaa Halawaa, executive director at Mubadala’s US venture group

The ven­ture crew at Mubadala are up­ping their biotech cre­ation game, tak­ing care­ful aim at a new fron­tier in drug de­vel­op­ment

It started with a cup of coffee and a slow burning desire to go early and long in the biotech creation business.

Wrapping up a 15-year discovery stint at Genentech back in the summer of 2021, Rami Hannoush was treated to a caffeine-fueled review of the latest work UCSF’s Jim Wells had been doing on protein degradation — one of the hottest fields in drug development.

“Jim and I have known each other for the past 15 years through Genentech collaborations. We met over coffee, and he was telling me about this concept of the company that he was thinking of,” says Hannoush. “And I got immediately intrigued by it because I knew that this could open up a big space in terms of adding a new modality in drug discovery that is desperately needed in pharma.”

Endpoints Premium

Premium subscription required

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

No­var­tis touts sev­en years of dura­bil­i­ty da­ta for Zol­gens­ma

The same day that Roche touted positive durability and safety data for its spinal muscular atrophy drug Evrysdi, Novartis also made a splash with its multi-million dollar gene therapy for the disease.

Novartis rolled out interim data from two long-term follow-up studies Monday at the 2023 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference. In the first study, LT-001, all children in the trial that were treated after showing symptoms of SMA “maintained all previously achieved motor milestones” up to 7.5 years after being dosed. The average time since Zolgensma was given was 6.86 years.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,400+ biopharma pros reading Endpoints daily — and it's free.

'Band­ing to­geth­er': 50 fe­male biotech ex­ec­u­tives lay out plans for board di­ver­si­ty, new com­pa­nies and men­tor­ing founders

Earlier this month, during the Silicon Valley Bank meltdown, Angie You recalled the speed with which female biotech CEOs were helping each other connect with bankers, get their wires through and assuage concerns during a financial implosion.

This past weekend, 50 of about 125 women who are part of that Slack group and a broader coalition self-dubbed the Biotech Sisterhood met in person in Cancun for the second rendition of an annual summit connecting female biotech CEOs. The attendance list doubled that of the inaugural gathering in Arizona 12 months ago.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,400+ biopharma pros reading Endpoints daily — and it's free.

Rohan Palekar, 89bio CEO

89bio’s PhII da­ta add to quick suc­ces­sion of NASH read­outs as field seeks turn­around

89bio said its drug was better than placebo at lessening fibrosis without worsening nonalcoholic steatohepatitis, or NASH, in two of three dose groups.

The San Francisco biotech said it thinks the Phase IIb data pave the way for a potential Phase III, following in the footsteps of another biotech in its drug class, Akero Therapeutics. To fund a late-stage study, CEO Rohan Palekar told Endpoints News 89bio “would need to raise additional capital,” with the company having about $188 million at the end of last year.

FDA in­di­cates will­ing­ness to ap­prove Bio­gen ALS drug de­spite failed PhI­II study

Ahead of Wednesday’s advisory committee hearing to discuss Biogen’s ALS drug tofersen, the FDA appeared open to approving the drug, newly released briefing documents show.

Citing the need for flexibility in a devastating disease like ALS, regulators signaled a willingness to consider greenlighting tofersen based on its effect on a certain protein associated with ALS despite a failed pivotal trial. The documents come after regulatory flexibility was part of the same rationale the agency expressed when approving an ALS drug last September from Amylyx Pharmaceuticals, indicating the FDA’s openness to approving new treatments for the disease.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,400+ biopharma pros reading Endpoints daily — and it's free.

Roche and Lil­ly team up to de­vel­op blood test to de­tect ear­ly signs of Alzheimer's

Eli Lilly is teaming up with Roche to help develop a blood test to detect early signs of Alzheimer’s disease and determine whether a patient should go for further confirmatory testing.

Roche’s Elecsys Amyloid Plasma Panel (EAPP) measures pTau 181 protein assay and APOE E4 assay in human blood plasma – elevations in pTau 181 are present in the early stages of Alzheimer’s, while the presence of APO E4 is the most common genetic risk factor for the disease.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,400+ biopharma pros reading Endpoints daily — and it's free.

Francesco Marincola, newly-appointed Sonata Therapeutics CSO

Kite's head of re­search leaves for Flag­ship start­up Sonata

Another leader is departing Kite Pharma, and will to spend the “last part” of his career exploring how cancer evades the immune system.

Kite’s senior VP and global head of cell therapy research Francesco Marincola left the Gilead CAR-T unit last week for Sonata Therapeutics. Flagship last May unveiled the startup, which was pieced together from two fledgling biotechs Inzen and Cygnal Therapeutics. As CSO, Marincola will lead Sonata’s push to reprogram cancer cells to make them more immunogenic.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,400+ biopharma pros reading Endpoints daily — and it's free.

Vipin Garg, Altimmune CEO

Al­tim­mune’s shares halved af­ter in­ter­im look at PhII weight loss drug da­ta

Altimmune’s attempt to catch up to Novo Nordisk and Eli Lilly’s GLP-1 drugs hit an investor snag Tuesday after the biotech shared interim Phase II weight loss data.

The Maryland biotech’s pemvidutide is a GLP-1/glucagon dual receptor agonist meant to activate GLP-1 receptors to squash appetite and glucagon to ramp up energy use. The 2.4 mg dose showed a placebo-adjusted weight loss of 9.7% at week 24 of 48, which Jefferies analysts said would be comparable to Novo Nordisk’s semaglutide (Wegovy) and Eli Lilly’s tirzepatide (Mounjaro).

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,400+ biopharma pros reading Endpoints daily — and it's free.