Nemvaleukin for Mucosal Melanoma Granted FDA’s Orphan Drug Status

Nemvaleukin alfa (nemvaleukin; formerly ALKS 4230), an interleukin-2 (IL-2) variant immunotherapy for the treatment of mucosal melanoma, has been granted orphan drug designation by the FDA, according to a press release from developer Alkermes plc.¹

Nevaleukin is a novel, investigational fusion protein made up of IL-2 and a high affinity IL-2 alpha receptor chain that is designed to selectively expand tumor-killing immune cells while also avoiding the activation of immunosuppressive cells. According to the press release, this is done by the cells binding to the intermediate-affinity IL-2 receptor complex. The sensitivity of the drug is designed to use the antitumor effects of existing IL-2 therapy while also mitigating certain limitations.

The safety, tolerability, and pharmacokinetics of nemvaleukin was evaluated in the ARTISTRY-1, ARTISTRY-2, and ARTISTRY-3 studies. ARTISTRY-1 (NCT02799095) focused on the safety and tolerability of nemvaleukin with or without added pembrolizumab (Keytruda), ARTISTRY-2 (NCT03861793) was a dose-escalation/expansion phase 1/2 study with or without pembrolizumab, and ARTISTRY-3 (NCT04592653) focused on the drug as a monotherapy and its effects on the tumor microenvironment. Each trial is open and exploring the use of the agent, as a monotherapy or in combination, in patients with solid tumors. Both intravenous and subcutaneous formulations are also explored across the ARTISTRY clinical trial program.

In ARTISTRY-1, patients were administered nemvaleukin as a monotherapy once daily for 5 days and in combination with pembrolizumab. Primary objectives included safety and anti-tumor activity.²

For the 36 patients who received the monotherapy, the maximum tolerated dose of the agent has not been reached and dose escalation continues. The majority of reported adverse events (AE) were pyrexia (75%) and chills (72%). The vast majority of AEs were grades 1-2.

ARTISTRY-2 is exploring the use of subcutaneous nemvaleukin administered in the back of the arm or abdomen with or without intravenous pembrolizumab. Primary end points of the study include AEs, serious AEs, and overall response rate.

ARTISTRY-3 has primary outcomes of changes in density of immune cells and changes in ratios based on immunohistochemistry. The phase 1/2 studies had primary endpoints of the severity, frequency, and characterization of adverse events. Secondary outcomes include complete response, duration of response, and incidents of serious AEs. The trial aims to enroll 36 patients and has a primary outcome of changes in density and ratios of T cells.¹

"This orphan drug designation is an important milestone for the nemvaleukin alfa program and underscores nemvaleukin's potential clinical utility in mucosal melanoma, a particularly aggressive form of melanoma for which treatment options remain limited," said Jessicca Rege, PhD, vice president, Head of Oncology at Alkermes, in a press release. "The accumulating data from the nemvaleukin program have continued to support the clinical profile we anticipated in targeting the IL-2 pathway, and we look forward to continuing our momentum with the ARTISTRY development program this year."

_References

_{1. Alkermes announces FDA orphan drug designation for Nemvaleukin Alfa for treatment of mucosal melanoma. News Release. March 11, 2021. Accessed March 11, 2021. https://investor.alkermes.com/news-releases/news-release-details/alkermes-announces-fda-orphan-drug-designation-nemvaleukin-alfa.}

_{2, Vaishampayan U, Muzzaffar J, Velcheti V, et al. ALKS 4230, an Engineered IL-2 Fusion Protein, in Monotherapy Dose-Escalation and Combination Therapy With Pembrolizumab in Patients With Solid Tumors: ARTISTRY-1 Trial. Poster presented at: 2019 Society for Immunotherapy of Cancer Annual Meeting; November 6-10, 2019; National Harbor, MD. Abstract P447.}