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.

Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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David Kirn, 4D Molecular Therapeutics CEO (via website)

FDA places hold on 4D Mol­e­c­u­lar’s Fab­ry gene ther­a­py

4D Molecular Therapeutics quietly tucked an FDA clinical hold on its Fabry gene therapy into an SEC filing.

Meanwhile, the biotech issued a press release the same day after the closing bell on Thursday touting an IND for another asset, in diabetic macular edema.

The California biotech had paused enrollment of patients in its two trials of the Fabry gene therapy (4D-310) last month after three patients experienced kidney issues, all of which were resolved within four weeks. At the time, 4DMT said it would wait until the second half of this year to look at 12-month clinical data on six patients in the Phase I/II trials, one in the US and one in Taiwan and Australia.

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Uğur Şahin, BioNTech CEO (Andreas Arnold/picture-alliance/dpa/AP Images)

BioN­Tech opens new plas­mid DNA man­u­fac­tur­ing fa­cil­i­ty in Ger­many

German mRNA player BioNTech opened the doors to a new manufacturing facility on Thursday, this one just about 75 miles north of its headquarters in Mainz, Germany.

BioNTech announced on Thursday that it has completed the construction of its first plasmid DNA manufacturing facility in Marburg, Germany. The facility will produce materials for mRNA-based vaccines and therapies along with cell therapies.

Teresa Graham, incoming Roche Pharmaceuticals CEO

In­com­ing Roche CEO builds out his top team, tap­ping Genen­tech vet to lead phar­ma di­vi­sion

Roche announced another leadership shuffle Thursday morning – the head of global product strategy, Teresa Graham, will take over as CEO of Roche Pharmaceuticals in March while the company’s corporate executive committee will make a spot for Levi Garraway, CMO and executive VP of global product development.

Thomas Schinecker will take over the top spot as Roche group CEO in March, leaving his spot as head of diagnostics.

FDA ap­proves GSK's ane­mia drug with safe­ty warn­ing — af­ter bat­ting back sim­i­lar drugs

GSK has secured the first of four US approvals it’s hoping for this year, as the FDA greenlit daprodustat as a treatment for anemia due to chronic kidney disease.

But the FDA limited the use of the drug, to be marketed as Jesduvroq, to patients who have been receiving dialysis for at least four months and stopped short of approving it for patients not dependent on dialysis — in line with the recommendations of the advisory committee it consulted.

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Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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Te­va drops out of in­dus­try trade group PhRMA

Following in AbbVie’s footsteps, Teva confirmed on Friday that it’s dropping out of the industry trade group Pharmaceutical Research and Manufacturers of America (PhRMA).

Teva didn’t give a reason for its decision to leave, saying only in a statement to Endpoints News that it annually reviews “effectiveness and value of engagements, consultants and memberships to ensure our investments are properly seated.”

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