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.

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. 

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.

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.