Dapirolizumab Pegol Does Not Meet Primary Endpoint, But Well-Tolerated, Shows Improvements in Disease Activity in SLE

For patients with moderate to severe active systemic lupus erythematosus (SLE), dapirolizumab pegol (DZP) may be well-tolerated and shows improvements in disease activity, despite not meeting the primary endpoint, according to study results published Rheumatology.

A team of investigators conducted a phase 2b, double-blind, placebo-controlled, randomized trial (RISE; ClinicalTrials.gov Identifier, NCT02804763) to determine the dose-response, efficacy, and safety profiles of DZP in patients with SLE.

Patients with moderate to severe active SLE receiving a stable dose of corticosteroids, antimalarials, or immunosuppressants were included in the analysis. Certain patients with lupus nephritis were also included. The first part of the investigation was a 24-week, double-blinded period in which patients received a placebo or intravenous DZP (6, 24, or 45 mg/kg) and standard-of-care treatment every 4 weeks. In the second part of the investigation following week 24, patients only received standard-of-care treatment until week 48.

The primary outcome was to determine a dose-response relationship across the 3 doses of DZP and placebo using the week 24 British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) responder rates. Secondary efficacy endpoints aimed to measure the BICLA responder rate in specific dose groups at week 24.

Of the 178 patients who completed the double-blind period of the analysis, 164 (90.1%) also completed the observational period of the study. Although patients in all 3 DZP groups had clinical and immunologic improvements compared with those in the placebo group, the BILCA responder rate did not fit the prespecific, dose-response models (P =.07).

At week 24, the cumulative number of BILAG severe flares were lower among all 3 DZP dose groups compared with the placebo group. During the observational period, SLE Disease Activity Index 2000 (SLEDAI-2K), physician’s global assessment, BILAG, and Cutaneous Lupus Erythematosus Disease Area and Severity Index responder rates declined after DZP withdrawal.

“Upon withdrawal of DZP, immunologic parameters generally worsened and returned to baseline levels, providing further evidence of DZP biologic activity, but challenging the capacity of DZP to induce tolerance,” the investigators noted.

Overall, DZP had an acceptable safety profile and was well-tolerated by the patient population. Of the 4 thromboembolic events that occurred during the first part of the analysis, 3 were reported among participants in the placebo group, suggesting that DZP treatment may be associated with a smaller risk for thromboembolism compared with other anti-CD40L treatments.

“[T]here is a need to widen the biologic repertoire available for the treatment of [patients with] SLE to reduce disease activity, prevent flares, and restrict accrual of organ damage,” the investigators wrote.

“The potential clinical benefit of DZP warrants further investigation in a larger study,” the researchers concluded.

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Furie RA, Bruce IN, Dörner T, et al. Phase 2, randomized, placebo-controlled trial of dapirolizumab pegol in patients with moderate-to-severe active systemic lupus erythematosus. Rheumatology. Published online May 6, 2021. doi:10.1093/rheumatology/keab381