Arie Belldegrun speaking at UKBIO19

Pa­tient death mars lat­est cut of da­ta from Al­lo­gene's off-the-shelf CAR-T

Al­lo­gene has been rid­ing high since AS­CO in May, when ear­ly da­ta showed their off-the-shelf CAR-T worked in a hand­ful of pa­tients and that no one re­ject­ed their for­eign cells. It was a key mo­ment in a field that could re­make cell ther­a­py and treat­ment for cer­tain can­cers.

On Wednes­day, though, the Arie Bellde­grun-found­ed biotech re­leased re­sults for their mul­ti­ple myelo­ma CAR-T and, al­though the re­spons­es were there, so was a red flag: Four pa­tients con­tract­ed a se­ri­ous in­fec­tion, and one of them died.

Al­lo­gene $AL­LO shares im­me­di­ate­ly fell from $33.79 to $28.78 Wednes­day morn­ing, al­though they would re­bound to $31.06 by the time mar­kets close.

The news is trag­ic on its own and a set­back for an ap­proach that Al­lo­gene is try­ing to prove can com­pete with or even out­per­form tra­di­tion­al mul­ti­ple myelo­ma CAR-Ts from J&J and Leg­end and from Bris­tol My­ers Squibb and blue­bird. Al­though Al­lo­gene and star­tups such as Po­sei­don have point­ed to the po­ten­tial for off-the-shelf ap­proach­es to be more scal­able and al­low for re­peat dos­ing, J&J and blue­bird have al­ready shown strong ef­fi­ca­cy in hu­man tri­als, set­ting the bar high.

Still, an­a­lysts were di­vid­ed on how large a role Al­lo­gene’s treat­ment played in the pa­tient’s death, or how con­cerned they should be if they are. The vol­un­teers in the Al­lo­gene tri­al were very sick, with many on their fifth-line of ther­a­py for a dead­ly can­cer, and pa­tients have died through­out the last decade of CAR-T tri­als, in­clud­ing in the blue­bird stud­ies.

Cowen’s Marc Frahm said it was “un­sur­pris­ing” news. “We would note that sev­er­al oth­er CAR T cell tri­als [saw] in­fec­tions in­clud­ing fa­tal events,” he wrote in a note to in­vestors.

The pa­tient was di­ag­nosed with se­vere pneu­mo­nia eight days af­ter re­ceiv­ing the ther­a­py, and in­ves­ti­ga­tors at­trib­uted it to the in­tense chemother­a­py pa­tients un­der­go di­rect­ly be­fore re­ceiv­ing the ther­a­py. They added that, as of the da­ta cut­off for the ab­stract, they had not seen oth­er ma­jor ad­verse events, in­clud­ing graft ver­sus host dis­eases — one com­mon and dam­ag­ing side ef­fect from oth­er form of cell trans­plants.

Jef­feries’ Biren Amin not­ed that, more broad­ly, “high in­fec­tion rate is a key fac­tor for mor­tal­i­ty in myelo­ma pa­tients.”

An­a­lysts, mean­while, were large­ly sat­is­fied with the ef­fi­ca­cy re­sults. Al­though it’s still ear­ly in Phase I, they ar­gued it showed the po­ten­tial to even­tu­al­ly com­pete with the J&J and blue­bird CAR-Ts.

In the high-dose arm of the dose-find­ing study, three out of five pa­tients re­spond­ed. One of the three had a strin­gent com­plete re­sponse and an­oth­er had a very good par­tial re­sponse.

That’s a pret­ty small sam­ple size to draw per­cent­ages from, but Frahm ar­gued it looked “sim­i­lar” to the rough­ly 65% VG­PR/CR re­sponse blue­bird saw in ear­ly stud­ies and the 88% VG­PR re­sponse J&J saw.

Amin said it showed high dos­es are need­ed for the ther­a­py to work. He said longer term, they’ll be look­ing for Al­lo­gene to match blue­bird’s Phase I re­sults. In that study, he not­ed, pa­tients across dose co­horts who had high BC­MA ex­pres­sion had an 89% re­sponse rate and a 22% com­plete re­sponse rate.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

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Lisa Deschamps, AviadoBio CEO

Ex-No­var­tis busi­ness head hops over to a gene ther­a­py start­up — and she's reeled in $80M for a dash to the clin­ic

Neurologist and King’s College London professor Christopher Shaw has been researching neurodegenerative diseases like ALS and collaborating with drugmakers for the last 25 years in the hopes of pushing new therapies forward. But unfortunately, none of those efforts have come anywhere close to fruition.

“So, you know, after 20 years in the game, I said, ‘Let’s try and do it ourselves,’” he told Endpoints News. 

Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Biospec­i­men M&A: Dis­cov­ery ac­quires Al­bert Li's he­pa­to­cyte project; PhI­II tri­al on Bay­er's Nube­qa reached pri­ma­ry end­point

Discovery Life Sciences has acquired what claims to be the Maryland-based host of the world’s largest hepatocyte inventory, known as IVAL, to help researchers select more effective and safer drug candidates in the future.

The combined companies will now serve a wider range of drug research and development scientists, according to Albert Li, who founded IVAL in 2004 and is set to join the Discovery leadership team as the CSO of pharmacology and toxicology.

Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Vas Narasimhan, Novartis CEO (Thibault Camus/Pool via AP Images)

With gener­ic com­pe­ti­tion heat­ing up, Vas Narasimhan out­lines No­var­tis' growth plans at R&D day

Thursday marks Novartis’ annual R&D day, and with it comes CEO Vas Narasimhan’s attempt to spotlight the company’s pipeline strategy and emerging stars.

The biggest question entering Thursday’s presentation dealt with how the big biopharma will make up revenues from upcoming generic competition — Novartis says within the next five years, generics will eat away roughly $9 billion in sales. To offset this, Narasimhan outlined a strategy for 4% growth or higher until 2026, focusing on six key medicines he believes will see multibillion dollar profits during this time.

In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

With on­ly burns to show in gene ther­a­py, Astel­las inks deal with AAV spe­cial­ist Dyno in push for a bet­ter cap­sid

On the hunt for a better AAV capsid for gene therapy, Eric Kelsic’s Dyno Therapeutics has set itself apart with its focus on machine learning to help speed discovery. Now, Japanese drugmaker Astellas — fresh off a slate of gene therapy burns — is taking a bet on Dyno as it looks to the future.

Astellas and Dyno will work together as part of an R&D pact to develop next-gen AAV vectors for gene therapy using Dyno’s CapsidMap platform directed at skeletal and cardiac muscle, the companies said Wednesday. Under the terms of the deal, Dyno will design AAV capsids for gene therapy, while Astellas will be responsible for conducting preclinical, clinical and commercialization activities for gene therapy product candidates using the capsids.