Add-on Therapy Anifrolumab Reduces Disease Activity in SLE Patients, Phase 3 Trial Shows

Adding anifrolumab to standard-of-care treatment led to a clinically meaningful reduction in disease activity at week 52 in patients with systemic lupus erythematosus (SLE), according to top-line results of a Phase 3 trial.

The TULIP 2 study (NCT02446899) assessed the safety and efficacy of AstraZeneca’s anifrolumab in 373 adults with moderate-to-severe SLE, who received 300 mg anifrolumab or a placebo by intravenous infusion every four weeks.

Reductions in disease activity were the trial’s primary endpoint (goal) and were assessed with the British Isles Lupus Assessment Group based Composite Lupus Assessment (BICLA), which requires improvement in all organs with disease activity at baseline, and no new flares.

The positive response in the study was in line with findings from another Phase 3 trial named TULIP 1 (NCT02446912), which placed 460 participants on a placebo or intravenous infusion of 150 or 300 mg of anifrolumab every four weeks, for a total of 13 doses. Similar to TULIP 2, the TULIP 1 trial also included SLE patients with moderate-to-severe disease activity who were receiving standard-of-care treatment.

However, TULIP 1 did not meet its primary goal of decreased disease activity when comparing anifrolumab to a placebo, as measured by the SLE Responder Index 4. This result led to the selection of the BICLA measure as the primary endpoint of TULIP 2.

The safety profile of anifrolumab in TULIP 2 was consistent with previous studies. AstraZeneca plans to present results from these two trials at an upcoming medical meeting.

“These are important results and we will now review the full data set and explore pathways to bring this potential new treatment to patients,” Mene Pangalos, AstraZeneca’s executive vice president of BioPharmaceuticals R&D, said in a news release. He also noted that only one new treatment has been approved in the last 60 years for SLE patients.

The results are encouraging, as they suggest “clinically significant disease activity reductions across multiple organ systems,” Susan Manzi, MD, Lupus Foundation of America board chair, said in another news release.

This finding “provides hope that another therapy may soon be added to the many treatments required to manage [SLE],” said Manzi, who’s also chair at the Allegheny Health Network Medicine Institute and director of its Lupus Center of Excellence.

Anifrolumab is a monoclonal antibody that targets the subunit 1 of the type I interferon receptor, blocking the activity of all type I interferons, which are pro-inflammatory molecules that include IFN-alpha, IFN-beta and IFN-omega. The excess levels of type I interferons found in most adults with SLE (60%-80%) have been correlated with disease activity.

“These exciting results from the TULIP 2 trial demonstrate that, by targeting the type I interferon receptor, anifrolumab reduced disease activity in patients with [SLE],” said Eric F. Morand, a principal investigator of TULIP 2 and professor at Monash University, Australia.

In addition to these two trials, the TULIP program includes a Phase 3 long-term extension study (NCT02794285) in SLE and a Phase 2 trial (NCT02547922) in lupus nephritis, a type of kidney inflammation and the most common organ-specific complication in people with SLE.