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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Bio­gen hit by ALS set­back with PhI­II fail­ure for tofersen — but fol­lows a fa­mil­iar strat­e­gy high­light­ing the pos­i­tive

Patients and analysts waiting to hear Sunday how Biogen’s SOD1-ALS drug tofersen fared in Phase III didn’t have to wait long for the top-line result they were all waiting for. The drug failed the primary endpoint on significantly improving the functional and neurologic decline of patients over 28 weeks as well as the extension period for continued observation.

In fact, there was very little difference in response.

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UP­DAT­ED: Boehringer nabs FDA's first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra com­peti­tor — but will it mat­ter?

The FDA late Friday awarded Boehringer Ingelheim the first interchangeability designation for its Humira biosimilar Cyltezo, meaning that when it launches in July 2023, pharmacists will be able to automatically substitute the Boehringer’s version for AbbVie’s mega-blockbuster without a doctor’s input.

The designation will likely give Boehringer, which first won approval for Cyltezo in 2017, the leg up on a crowded field of Humira competitors.

Reshma Kewalramani, Vertex CEO (YouTube)

Ver­tex gets much-need­ed win with ‘ex­tra­or­di­nary’ first pa­tient re­sults on po­ten­tial di­a­betes cure

Vertex said Monday that the first patient dosed with its cell therapy for type 1 diabetes saw their need for insulin injections vanish almost entirely, a key early step in the decades-long effort to develop a curative treatment for the chronic disease.

The patient, who had suffered five potentially life-threatening hypoglycemic — or low blood sugar — episodes in the year before the therapy, was injected with synthetic insulin-producing cells. After 90 days, the patient’s new cells produced insulin steadily and ramped up their insulin production after a meal like normal cells do, as measured by a standard biomarker for insulin production.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'

 

Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Two drug­mak­ers hit with PDU­FA date de­lays from FDA amid back­log of in­spec­tions

As the FDA is weighed down with more and more pandemic responsibilities, the agency is beginning to miss PDUFA dates with more frequency too. Two different companies on Monday said they received notices that the FDA has not completed their drug reviews on time.

The review of an NDA for Avadel Pharmaceuticals’ candidate treatment for narcolepsy is not coming this month, the company said, and the review of UCB’s BLA for bimekizumab, used to treat moderate to severe plaque psoriasis, will miss its target date as well.

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Terrie Curran, Phathom CEO (Credit: Arcutis)

Phath­om's old Take­da drug bests Pre­vacid in a PhI­II GI tri­al. Next stop? The FDA

There’s no time for rest in biopharma — at least not at Phathom Pharmaceuticals. Just over a month after submitting two NDAs for its lead acid-fighter vonoprazan, the biotech is already lining up a third, and collecting an extra $50 million to push things along.

Vonoprazan met its primary non-inferiority endpoints in a Phase III study comparing it to standard-of-care Prevacid in a type of gastroesophageal reflux disease (GERD) called erosive esophagitis (EE). It also proved superior to the popular heartburn drug by multiple measures, including healing rate and maintenance of healing.

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In a first, a small runner-up vaccine developer says its own Covid-19 jab has induced “superior neutralizing antibody titer levels” over AstraZeneca’s AZD1222 when pitted head-to-head in a Phase III trial.

That and non-inferiority in seroconversion rate were the co-primary endpoints of the trial, which recruited 4,012 adult volunteers across the UK.

But on the exploratory endpoint of Covid-19 case counts, Valneva notes that both treatment groups saw a similar number of infections.