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.
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.
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.