CMC holdup de­lays Io­vance fil­ing again — to 2022 — as FDA seeks more as­say da­ta for TIL ther­a­py

Re­mem­ber those po­ten­cy as­says that tripped up Io­vance’s prepa­ra­tions for a BLA fil­ing? It turns out they may take even longer than ex­pect­ed to re­solve.

In a brief state­ment, the com­pa­ny di­vulged that the FDA wants to see more da­ta on the as­says — used to en­sure each batch of its tu­mor-in­fil­trat­ing lym­pho­cyte ther­a­py is up to stan­dard — in ad­di­tion to what it’s al­ready sub­mit­ted. Io­vance is now plan­ning to file for ap­proval in the first half of 2022, which amounts to a de­lay of more than a year from the orig­i­nal time­line of sub­mit­ting in 2020.

Maria Fardis

CEO Maria Fardis high­light­ed the fact that li­fileu­cel, which is ini­tial­ly be­ing de­vel­oped for PD-1 re­frac­to­ry melanoma, rep­re­sent­ed the first cell ther­a­py in sol­id tu­mors to reach the fin­ish line. Al­though an­a­lysts still large­ly ex­pect them to get there even­tu­al­ly, some in­vestors fret­ted, dri­ving shares $IO­VA down 6.79% to $26.97 post­mar­ket.

“As such, TIL prod­uct is com­plex by na­ture and align­ment with FDA on a po­ten­cy as­say is an im­por­tant step to­ward BLA sub­mis­sion,” she said in a state­ment.

De­signed for one-time ad­min­is­tra­tion, Io­vance’s prod­uct con­sists of TILs ex­tract­ed from the pa­tients’ own tu­mors and then ex­pand­ed ex vi­vo — with the help of IL-2. The cur­rent man­u­fac­tur­ing process is de­scribed as a sec­ond-gen­er­a­tion it­er­a­tion to the pi­o­neer­ing ap­proach de­vel­oped by Steven Rosen­berg at the Na­tion­al Can­cer In­sti­tute, with its own fa­cil­i­ty to com­ple­ment some con­tract pro­duc­tion.

In tri­als across melanoma, cer­vi­cal can­cer and even lung can­cer, TIL ther­a­py spurred promis­ing over­all re­sponse rates.

While ex­ecs have pre­vi­ous­ly sug­gest­ed a speedy reg­u­la­to­ry path for the cer­vi­cal in­di­ca­tion, an­a­lysts ex­pect the fil­ing there will al­so be de­layed.

Io­vance is not alone. In a field where it’s of­ten said that your process is your prod­uct, even the lead­ing cell ther­a­py de­vel­op­ers have run in­to their share of chem­istry, man­u­fac­tur­ing and con­trol is­sues. Bris­tol My­ers Squibb and blue­bird learned it the hard way as the FDA slammed them with a sur­prise refuse-to-file let­ter cit­ing a faulty sec­tion on CMC — al­though they still se­cured pri­or­i­ty re­view and ul­ti­mate­ly ap­proval.

“We see this as main­tain­ing reg­u­la­to­ry risk, though our dis­cus­sions with ex­perts fa­mil­iar with po­ten­cy as­say de­vel­op­ment in cell and gene ther­a­pies see res­o­lu­tion of this type of is­sue as a mat­ter of when, not if,” Mizuho an­a­lyst Mara Gold­stein wrote in a note.

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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Janet Woodcock (AP Images)

Janet Wood­cock plots her fu­ture at FDA, with se­nior ad­vi­sor role to fall back on if Califf wins con­fir­ma­tion

Acting FDA commissioner Janet Woodcock has been the face of just about every drug approval decision at the agency since the turn of the century. Since the pandemic began, she’s moved between the top of the drugs center to the head of therapeutics at Operation Warp Speed, leading the drive for work on Covid-targeted mAbs and antivirals.

Looking forward — and pending a quick Senate confirmation to cement Rob Califf’s return to the top of FDA early next year — Woodcock’s role at the agency will again be in flux.

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Richard Pazdur (via AACR)

Ac­cel­er­at­ed ap­proval re­forms need mean­ing­ful con­fir­ma­to­ry tri­al im­prove­ments, pro­fes­sors write in Sci­ence

Outside of Covid-19, 2021 has been the year of the accelerated approval.

Beginning last spring, FDA openly challenged six “dangling” accelerated approvals (hadn’t confirmed their clinical benefit yet), three of which were later pulled by the companies.

Then in June, FDA pulled out the accelerated approval pathway, seemingly out of nowhere, to sign off on Biogen’s controversial Alzheimer’s drug Aduhelm. It hadn’t even been mentioned at the drug’s adcomm.

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.