Commercial stage biotech drug developer Immunocore Holdings announced on Wednesday that the FDA has granted marketing approval for KIMMTRAK (tebentafusp-tebn) for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM), making it the only FDA-approved treatment specifically targeting the disease.
The drug also becomes the first T cell receptor (TCR) therapeutic to receive regulatory approval from the agency and the first bispecific T cell engager to receive regulatory approval from the FDA to treat a solid tumor. According to Bahija Jallal, CEO of Immunocore, the approval of its TCR candidate “validates the strength of our platform and opens doors for us to explore further breakthrough discoveries in TCR therapeutics for the treatment of other cancers and diseases with high unmet need.”
Immunocore executives, in a conference call Wednesday announcing the approval, said bringing the TCR therapeutic to market was 15 years in the making for the biotech company. In addition to the FDA, the company said that the European Medicines Agency (EMA), the United Kingdom’s Medicines and Healthcare Regulatory Agency (MHRA), Health Canada, and the Australian Government Department of Health Therapeutic Goods Administration (TGA) have accepted the submission of its Marketing Authorization Application. Additionally, to meet the unmet therapeutic need, the company is running an early access program that currently counts more than 200 patients in 13 countries that are already receiving the benefit of the drug.
“Uveal melanoma is a devastating disease that has historically resulted in death within a year of metastasis for our patients,” said John Kirkwood, director of the Melanoma Center at the UPMC Hillman Cancer Center, Pittsburgh. “The approval of KIMMTRAK represents a major paradigm shift in the treatment of metastatic uveal melanoma, and for the first time offers hope to those with this aggressive form of cancer.”
The approval was based on the results of the Phase III IMCgp100-202 clinical trial, published on September 23, 2021 in the New England Journal of Medicine. The randomized pivotal trial evaluated overall survival (OS) of KIMMTRAK compared to investigator’s choice (either pembrolizumab, ipilimumab, or dacarbazine) in patients with previously untreated mUM. 378 patients were randomized in a 2:1 ratio to either KIMMTRAK or investigator’s choice. Data from the trial, showed that KIMMTRAK demonstrated median OS benefit as a first-line treatment. The OS Hazard Ratio (HR) in the intent-to-treat population favored KIMMTRAK, HR=0.51 (95% CI: 0.37, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 13% ipilimumab; 6% dacarbazine). In the clinical trials, across both arms, patients stopped treatment for disease progression, unless the patient was otherwise deriving benefit, or for unacceptable toxicity.
Treatment-related adverse reactions were manageable and consistent with the proposed mechanism. In the 245 patients treated with KIMMTRAK, Grade 3 cytokine release syndrome (CRS) occurred in less than 1% of patients and were generally well-managed. There were no Grade 4 or fatal CRS events observed in the Phase 3 trial, but a boxed warning will be included for CRS as it has the potential to become serious or life-threatening if not managed appropriately.
Mohammed Dar, head of clinical development and chief medical officer of Immunocore said that approximately 1,700 people in the US are diagnosed with uveal melanoma each year. “Not only does this diagnosis mean loss of vision in the affected eye, but it also begins an anxiety filled watching period to see if that uveal melanoma will come back,” he said in the conference call. “Unfortunately, in about 50% of cases, the disease does come back and, when it does, it metastasizes—usually to the liver. Until today, these patients were then told by their physician that there were no FDA approved therapies specific for this dreadful disease and that the median survival was only about a year.”
Like many first-in-class cancer drugs, a course of treatment for KIMMTRAK is expected to run into six figures. “The wholesale acquisition cost of a 100 microgram vial of KIMMTRAK is $18,760 based on a median duration of treatment of 5.3 months,” noted Ralph Torbay, head of commercial at Immunocore. “As observed in our phase three clinical trial, we expect a median total cost of contract to be around $400,000.”
This price does not include mandatory discounts, and the company has established KIMMTRAK Connect, a patient assistance program that provides both medical assistance through its own nursing staff, as well as financial assistance designed to provide access to patients regardless of their financial status.
