Nektar Therapeutics Announces Phase 2 Topline Data for Rezpegaldesleukin in Patients with Systemic Lupus Erythematosus

Nektar Therapeutics today announced topline data from a Phase 2 randomized, double-blind, placebo-controlled study of rezpegaldesleukin (also known as LY3471851 or REZPEG) in adults with moderately-to-severely active systemic lupus erythematosus (SLE) despite receiving standard-of-care treatment such as corticosteroids, anti-malarials, and non-biological immunosuppressants. REZPEG is an investigational, potential first-in-class selective regulatory T-cell inducing IL-2 conjugate designed to treat select autoimmune diseases.

The Phase 2 ISLAND study enrolled 291 adults with moderate-to-severe SLE. The study consisted of three arms evaluating rezpegaldesleukin administered subcutaneously at different doses (low-dose of 300mcg Q2W, mid-dose of 900mcg Q2W, high-dose of 1800mcg Q2W) compared to placebo. The primary endpoint of the study was a 4-point reduction in the SLEDAI-2K score in pre-defined study populations. Although the mid-dose level demonstrated a numeric improvement in SLEDAI-2K score as compared to placebo (with a placebo-adjusted response of 8.8% for the modified intent-to-treat (mITT) population [p=0.309] and 13.9% for the per protocol population [p=0.06]), the primary endpoint was not met. The placebo-adjusted responses for the low- and high-doses were less than those of the mid-dose for both populations.

The mid-dose level in the study also demonstrated consistent and potentially clinically meaningful improvements for the majority of secondary clinical endpoints in patients treated with REZPEG compared with placebo, including the endpoints of British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) response (with a placebo-adjusted response of 16.4% for the mITT BICLA-evaluable population and 19.1% for the per protocol BICLA-evaluable population) and Lupus Low Disease Activity State (LLDAS) (with a placebo-adjusted response of 12.2% for the mITT population and 15.1% for the per protocol population). The placebo-adjusted responses for BICLA and LLDAS for the low and high doses were less than those of the mid-dose for both populations.

Biomarker data demonstrated REZPEG led to dose-dependent proliferation of T regulatory cells, which was consistent with prior studies. Lilly has notified Nektar that they do not intend to advance REZPEG to Phase 3 development for SLE. Nektar and Lilly plan to work together to determine next steps for the planned Phase 2b study in atopic dermatitis.

“We believe that these study results seen in the ISLAND study show that rezpegaldesleukin had a positive impact on disease activity in patients with moderately-to-severely active systemic lupus erythematosus (SLE),” said Brian Kotzin, Chief Medical Officer of Nektar Therapeutics. “These data also further support rezpegaldesleukin’s ability to expand regulatory T cells and the potential for this T regulatory cell stimulator to be used as a novel approach in the field of autoimmune disease.”

Most adverse events reported were mild or moderate in severity.