Lethal­ly se­vere neu­ro­tox­i­c­i­ty con­tin­ues to haunt Juno’s CAR-T pipeline

With the on­col­o­gy world look­ing for an up­date on the lead­ing CAR-T play­ers at ASH af­ter Juno Ther­a­peu­tics $JUNO put its lead pro­gram for JCAR015 back on clin­i­cal hold fol­low­ing 2 new deaths from cere­bral ede­ma, the biotech was forced to con­cede Sat­ur­day that in­ves­ti­ga­tors had tracked 6 cas­es of se­vere, grade 3-5 neu­ro­tox­i­c­i­ty out of 24 pa­tients in a sep­a­rate JCAR014 tri­al for chron­ic lym­pho­cyt­ic leukemia. And one of the pa­tients died af­ter de­vel­op­ing grade 5 cy­tokine re­lease syn­drome and cere­bral ede­ma (brain swelling).

On the up­side, 15/17 (88%) of evalu­able pa­tients had a com­plete mar­row re­sponse by flow cy­tom­e­try. “Four­teen of the com­plete bone mar­row re­sponse pa­tients had a re­sponse as­sess­ment by the more sen­si­tive method of IgH deep se­quenc­ing, with 7/14 (50%) hav­ing no de­tectable dis­ease. All sev­en of these pa­tients are alive and pro­gres­sion free with fol­low-up rang­ing from 3 to 26 months.”

Juno has al­ready not­ed a death from cere­bral ede­ma in a pa­tient tak­ing JCAR014 late last year. An­oth­er 5 have oc­curred among the JCAR015 group. The to­tal num­ber of deaths linked to cere­bral ede­ma in the JCAR014 and JCAR015 tri­als is now 7.

The most re­cent death in­volved a pa­tient who had re­ceived a cy/flu con­di­tion­ing reg­i­men. Juno had re­moved flu­dara­bine from its mix for JCAR015 in the sum­mer, telling an­a­lysts and the FDA that the elim­i­na­tion of flu would pre­vent the threat of cere­bral ede­mas. But it didn’t work, leav­ing the com­pa­ny un­der a cloud as it at­tempts to ex­plain what went wrong, and how it might af­fect the rest of their work.

Juno has been us­ing its clin­i­cal work on JCAR014 to in­form re­searchers on how to pro­ceed with JCAR017, a sim­i­lar treat­ment that may well soon be the lead pro­gram if the biotech opts to scrap the trou­bled JCAR015, which looms as a dis­tinct pos­si­bil­i­ty.

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

'Chang­ing the whole game of drug dis­cov­ery': Leg­endary R&D vet Roger Perl­mut­ter leaps back in­to work as a biotech CEO

Roger Perlmutter needs no introduction to anyone remotely involved in biopharma. As the R&D chief first at Amgen and then Merck, he’s built a stellar reputation and a prolific career steering new drugs toward the market for everything from cancer to infectious diseases.

But for years, he’s also held a less known title: science partner at The Column Group, where he’s regularly consulted about the various ideas the VCs had for new startups.

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UP­DAT­ED: Pfiz­er hits the brakes on their piv­otal tri­al for a BC­MA/CD3 bis­pe­cif­ic on safe­ty con­cerns while FDA road­block is hold­ing up Duchenne MD PhI­II

Pfizer’s ambitious plan to take a Phase II study of its BCMA CD3-targeted bispecific antibody elranatamab (PF-06863135) and run it through to an accelerated approval has derailed.

The pharma giant said in a release this morning that they have halted enrollment for their MagnetisMM-3 study after researchers tracked three cases of peripheral neuropathy in the ongoing Phase I. They are now sharing info with the FDA as they explore the red safety flag.

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Stéphane Bancel at the Endpoints #JPM20 breakfast panel in San Francisco, January 2020 (Photo: Jeff Rumans, Endpoints News)

Mod­er­na says Covid-19 vac­cine boost­er in­creased im­mune re­sponse against vari­ants of con­cern

About a month after announcing their variant-specific Covid-19 vaccine boosters showed promising results in mice, Moderna says it now has some human data to back it up.

Volunteers given a booster shot about six to eight months after receiving their second dose saw increased antibody levels against SARS-CoV-2 and two variants of concern: B.1.351, which was first identified in South Africa, and P.1, first identified in Brazil, the company said on Wednesday.

FDA ex­tends re­search agree­ment with MIT-li­censed or­gan-on-chip sys­tems

The FDA on Wednesday extended its four-year agreement with CN Bio, a developer of single- and multi-organ-on-chip systems used for drug discovery, for another three years.

CN Bio said the scope of the research performed by the FDA’s Center for Drug Evaluation and Research has expanded to include the exploration of the company’s lung-on-a-chip system to help with the agency’s evaluation of inhaled drugs, in addition to the agency’s work on its liver model.

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In quest to meet user fee goals, FDA’s per­for­mance con­tin­ues down­ward trend

A recent update to the FDA’s running tally of how it’s meeting its user fee-related performance goals during the pandemic shows an agency that is not out of the woods yet.

The latest numbers reveal that for a second straight quarter in 2021, the FDA has met its user fee goal dates for 93% of original new drug applications, which compares with 94% and 98% for the previous two quarters in 2020, respectively.

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Cynthia Butitta (L) and Joe Jimenez

Is that an­oth­er IPO in the mak­ing? Ex-No­var­tis CEO Joe Jimenez and a lead Kite play­er take up new posts at an off-the-shelf ri­val to 2 pi­o­neer­ing drugs

Right on the heels of taking on a $160 million crossover round in a likely leap to Nasdaq, Century Therapeutics CEO Lalo Flores is now pushing ahead with the high-profile ex-Novartis chief Joe Jimenez as chairman.

Jimenez’s greatest fame at Novartis was earned for one of its weakest products, as their pioneering personalized CAR-T Kymriah won the honors for the first such drug to make it to the market. Now a host of players, including Century, are barreling in behind the frontrunners with allogeneic rivals that can be created for off-the-shelf use.

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Joe Wiley, Amryt CEO

A biotech with a yen for pricey rare dis­ease drugs — and bar­gain base­ment shop­ping — adopts an­oth­er or­phan in lat­est M&A pact

After making it through a long, painful haul to get past a CRL and on to an FDA approval last summer, little Chiasma has found a buyer.

Amryt $AMYT, a company known for its appetite for acquiring expensive drugs for rare diseases at bargain prices, snagged Chiasma and its acromegaly drug Mycapssa (octreotide) capsules in an all-stock deal — with an exchange of 0.396 shares of Amryt for every share of Chiasma.

Ngozi Okonjo-Iweala, Director general of WTO (AP Photo/Keystone/Alessandro Della Bella)

Opin­ion: Waiv­ing Covid-19 vac­cine IP could save lives, but where is the man­u­fac­tur­ing ca­pac­i­ty?

Droves of House Democrats in Washington and members of the European Parliament have now glommed onto a major push by India and South Africa at the WTO to abolish all IP around Covid-19 vaccines.

At first blush, waiving this IP sounds like an easy win: More Covid-19 vaccines made locally for more people means more lives saved. Simple enough, especially as low-income countries have received just a tiny fraction of the world’s vaccine allotment so far.