Can Iovance Biotherapeutics TILt the balance in favour of approval?

GlobalData Healthcare 3 November 2020 (Last Updated November 3rd, 2020 09:58)

Can Iovance Biotherapeutics TILt the balance in favour of approval?

Iovance Biotherapeutics’ tumour-infiltrating lymphocyte (TIL) therapy, lifileucel, continues to show promising results in advanced melanoma patients who have previously progressed on systemic therapy. However, hopes of submission of a Biologics License Application (BLA) in 2020 were dashed recently, when the company announced that discussions with the FDA regarding potency assays were ongoing. Despite this setback, this first-in-class therapy is on track for potential approval as early as 2022.

Iovance Biotherapeutics facing some difficulty with its BLA filing is not necessarily surprising given the complexity of the therapy. Granted, the results generated so far are compelling, and the necessary duration of follow-up has already been agreed with the FDA. However, the assays used to define the therapy are currently a point of contention. Lifileucel is composed of TILs that are isolated from patient biopsies. TILs that can specifically target the tumour are then expanded and reinfused into the patient. Thus, this therapy is by definition unique, making attempts to assess the potential potency (including the strength, activity, and stability) of individual samples complicated. However, Iovance remains confident that these issues can be resolved by refining current assays and developing new ones, suggesting that the task, while not insignificant, is achievable. Investors also seem equally unworried; after an initial fall, stock prices are now higher than they were before the announcement of the delayed BLA filing.

The results from Iovance’s pivotal Phase II trial (NCT02360579) with Stage III/IV melanoma patients are certainly impressive. Patients who progress on either PD-1 or BRAF/MEK inhibitors are notoriously difficult to treat. In this Phase II pivotal trial, the mean number of therapies prior to trial enrollment was 3.3. Despite this, at the 2020 American Society of Clinical Oncology meeting, Iovance reported long-term data for Cohort 2 showing an overall response rate of 36% (N = 66 patients). Additionally, a complete response was seen in two patients, and the median duration of response had not yet been reached at 18.7 months of study follow-up. What’s more, responses were seen across age groups, and regardless of BRAF status, and PD-L1 levels. Lastly, side effects occurred early on (following the single-dose treatment) and were transient.

Should Iovance succeed in gaining approval for second-line treatment of advanced melanoma patients, it is well placed to expand into other solid tumours. Lifileucel is also in trials for the treatment of cervical cancer (pivotal) and for head and neck cancer (Phase II), with similarly promising results, albeit with smaller cohorts. Although the delay in the BLA submission is unfortunate, it is doubtful to hold Iovance back for long, and upon approval, lifileucel has the potential to transform second-line treatment in a whole host of notoriously difficult-to-treat patient groups.