Iovance To Press Ahead With Melanoma Cell Therapy Filing Despite Doubters
Still Expects To File In 2022
Executive Summary
Iovance has seen its share price collapse after releasing data from a second melanoma patient cohort – but is confident its potential first-in-class therapy is approvable.
Iovance Biotherapeutics has seen its share price dive after releasing new data from its potential first-in-class tumor-infiltrating lymphocyte (TIL) candidate lifileucel, but is still pressing ahead with a planned filing later this year.
The company is currently down by 57% to $6.90 with around $1bn wiped from its market value since investors responded negatively to new data from a registrational cohort of its Phase II C-144-01 study on 27 May.
The potential first-in-class cell therapy is being tested in patients with advanced (unresectable or metastatic) melanoma who failed prior anti-PD-1/L1 treatment, and who progressed after BRAF or BRAF/MEK inhibitor therapy (if BRAF+ cutaneous cancers).
The read-out in its lead indication in advanced melanoma was deemed less favorable than previous results seen in an earlier cohort from the same C-144-01 study. However, the company maintains this can be easily explained by the latest cohort of patients being considerably sicker.
The newly unveiled Cohort 4 data showed an objective response rate (ORR) of 29%, including three complete responses and 22 partial responses. The median duration of response (DOR) was 10.4 months after a median study follow-up of 23.5 months.
These data were not as strong as those from Cohort 2 (n=66), presented at ASCO last year, where lifileucel treatment exhibited an ORR of 35%, with five complete responses and 18 partial responses. The median DOR in Cohort 2 was not reached after a median study follow-up of 36.6 months
Iovance’s chief medical officer, Friedrich Graf Finckenstein, explained to analysts on a conference call that Cohort 4 patients had more advanced disease. More of these patients had elevated baseline lactate dehydrogenase (LDH) levels (64.4% versus 40.9%), and increased number of tumor lesions, indicating a higher baseline disease burden.
The cumulative duration of prior anti-PD-1 treatment was also twice as long in Cohort 4 patients, which influenced the duration of response. When combining the results from the two cohorts in a total of 153 patients, the ORR was 31%, and the DOR had not been reached at the median study follow-up of 27.6 months.
These results are giving Iovance the confidence to press ahead with a filing to the US Food and Drug Administration as planned in August 2022, with further additional data expected at an upcoming medical meeting in the second half of the year.
TILs are a part of the body’s natural defenses against cancer and describe a range of lymphocytic cells that invade solid tumor tissue, including ‘killer’ cytotoxic (CD8+) and helper (CD4+) T-cells, plus B- and Natural Killer (NK) cells.
Iovance’s platform works by extracting TILs from an individual cancer patient’s tumor, expanding and rejuvenating them before reinfusing them into the patient.
If approved in melanoma, lifileucel would become the first approved one-time cell therapy for a solid tumor cancer. The company would then aim to expand into other solid tumor targets. The next most advanced of these is the C-145-04 study in post chemo and post-chemo and PD-1 therapy cervical cancer patients.
The company is no stranger to oversized share price fluctuations, however. Its market value hit a pandemic-assisted peak of $52 a share in January 2021, but tumbled in April when the FDA requested extra data on its assays and again the following month when its CEO Maria Fardis unexpectedly departed. The firm has still not appointed a permanent leader, with Frederick Vogt currently serving as interim CEO and general counsel.
Despite the negative market sentiment, Joseph Pantginis, analyst at H.C. Wainwright commented in a 27 May note that the outlook for the firm was promising. “We believe that lifileucel is close to the finish line in metastatic melanoma patients, and we look forward to learning about its regulatory steps and the company´s launching preparations,” he wrote.
The drug has a special RMAT designation from the FDA, which could provide it with a fast-track approval as early as the second quarter of 2023. Analysts at JMP were also upbeat about the company’s prospects, and forecast a peak risk-adjusted revenue of around $1.93bn by 2027.