Mixed Results for Rezpegaldesleukin in Patients with Active SLE

Rezpegaldesleukin is a PEGylated conjugate of recombinant human interleukin (IL) 2 designed to treat patients with select autoimmune diseases. The agent is being investigated in phase 2 clinical trials as a treatment for systemic lupus erythematosus (SLE), atopic dermatitis and another unannounced autoimmune indication.¹

The overall results from a double-blind, placebo-controlled study (NCT04433585) showed that adult patients with moderate to severe active SLE taking rezpegaldesleukin did not experience a reduction disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). These results occurred despite patients also receiving standard-of-care treatment, which included corticosteroids, anti-malarial agents and non-biological immunosuppressant agents.² (Note: The study’s primary study end point was a four-point reduction in the SLEDAI-2K score in the pre-defined study populations.²)

Additionally, researchers observed a numeric improvement in the SLEDAI-2K score in patients taking a 900 mcg dose of subcutaneous rezpegaldesleukin every two weeks (mid-dose) compared with placebo. The study’s other rezpegaldesleukin dosing regimens were 300 mcg given subcutaneously every two weeks (low dose) and 1,800 mcg given subcutaneously every two weeks (high dose).

When compared with patients who received placebo, the patients who received 900 mcg of subcutaneous rezpegaldesleukin every two weeks showed consistent and potentially clinically meaningful improvements for most of the study’s secondary end points, including a British Isles Lupus Assessment Group (BILAG) Based Composite Lupus Assessment (BICLA) response and Lupus Low Disease Activity State (LLDAS). The placebo-adjusted responses for BICLA and LLDAS for the low- and high-dose treatment regimens were less than those of the 900 mcg mid-dose treatment regimen.

Results for Study Populations

In the study, the modified intent-to-treat (mITT) population was defined as all patients who were randomized to receive at least one dose of rezpegaldesleukin. The per protocol population was defined as all randomized patients who did not commit an Important Protocol Deviation that could compromise efficacy results.

Although the study overall found rezpegaldesleukin did not achieve its primary end point, researchers did observe reduced disease activity scores in a small number of patients. Here are some important details for both the primary and secondary clinical end points for patients who received the mid-dose regimen:

• In the mITT population, 8.8% of patients (placebo adjusted, P=0.309) achieved a reduction of at least four points in SLEDAI-2K score at week 24. In the per protocol population, 13.9% of patients (placebo adjusted, P=0.06) achieved a reduction of at least four points in the SLEDAI-2K score at week 24;
• In the mITT population, 8.8% of patients (placebo adjusted) achieved a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) response at week 24. In the per protocol population, 13.9% of patients (placebo adjusted) achieved an SRI-4 response at week 24;
• In the mITT, BICLA-evaluable population, 16.4% of patients (placebo adjusted) achieved a BICLA response at week 24. In the per protocol BICLA-evaluable population, 19.1% of patients (placebo adjusted) achieved a BICLA response at week 24; and
• At week 24, 12.2% of patients (placebo adjusted) in the mITT population achieved a LLDAS response, whereas 15.1% of patients (placebo adjusted) in the per protocol population achieved a LLDAS response in that timeframe.

Adverse Events

In the study, most adverse events, including arthralgias, fatigue, fevers, injection site reactions and pain, were mild or moderate in severity. A dose-dependent increase in adverse events was observed. Infection rates were similar between rezpegaldesleukin-treated patients and those who received placebo.