Iovance eyes November FDA decision on melanoma cell therapy

Iovance Biotherapeutics could be a few months away from a first regulatory approval for lifileucel, which could be the first cell-based therapy for a solid tumour in the US.

The FDA has formally started a priority review of the tumour-infiltrating lymphocyte (TIL) therapy with an action date of 25th November as a one-time, individualised therapy for people with advanced melanoma. And, for now, the FDA isn’t planning to hold an advisory committee meeting.

That could be viewed as a positive development for Iovance, as it tries to blaze the trail for cell therapies in solid tumours and mirror the success of CAR-Ts in blood cancers.

Originally developed by researchers at the National Cancer Institute (NCI) in the US, treatment with lifileucel follows a similar pathway to CAR-Ts. Lymphocytes are harvested from the body, exposed to interleukin-2 to boost their growth and activate them, and then reinfused into the patient.

Unlike CAR-T therapies, however, they don’t need to be genetically modified, which the company says simplifies and shortens the manufacturing process, although it remains complex and Iovance has faced issues developing potency assays for quality control purposes.

A couple of years ago, Iovance was riding high on preliminary data for lifileucel in melanoma, which showed a 36% objective response rate (ORR) in the C-144-01 study in unresectable or metastatic melanoma patients who had progressed on prior immunotherapy with PD-1/PD-L1 inhibitors or targeted treatment with BRAF or BRAF/MEK inhibitors, with a duration of effect of around 36 months.

That generated some predictions of blockbuster sales for the therapy among analysts. However, this time last year, the optimism about the programme was dented by additional data that raised questions about lifileucel’s durability, with an ORR of 29% for a second cohort in the study and a duration of 10.4 months.

The results wreaked havoc with Iovance’s share price, amid suggestions the therapy may still be approved, though struggle to find a commercial market without stronger data.

Iovance is already in the final stages of preparing a confirmatory phase 3 study called TILVANCE-301, which could provide a better picture of its efficacy in relapsed/refractory melanoma. At the same time, it may serve as a registrational trial to move lifileucel into frontline advanced melanoma therapy in combination with Merck & Co’s PD-1 inhibitor Keytruda (pembrolizumab).

The company is moving ahead with its commercialisation plans, and last year signed an agreement to acquire worldwide rights to IL-2 therapy Proleukin from Clinigen. That will provide its own supply of the drug as it builds towards a potential lifileucel launch, reducing the cost of clinical trials and cost of goods for the therapy, as well as providing a revenue stream.

The deal includes an upfront cost of around $200 million, with another $50 million payable on lifileucel’s approval in melanoma. Iovance ended the first quarter of this year with $632 million in cash reserves.

The company is also developing a follow-up TIL therapy for non-small cell lung cancer (NSCLC), called LN-145, and recently reported preliminary clinical results as a first-line therapy alongside Keytruda that it hopes will support regulatory filings. Another cervical cancer candidate is in early-stage development.