Anifrolumab Fails to Reduce Disease Activity in SLE, Phase 3 Trial Shows
Anifrolumab, MedImmune‘s investigational antibody being developed to treat systemic lupus erythematosus, is no better than placebo at reducing disease activity, results from the pivotal TULIP 1 Phase 3 clinical trial show.
“The result of this trial is disappointing for patients and the lupus community,” Sean Bohen, MD, PhD, said in a press release. Bohen is executive vice president, global medicines development, and chief medical officer at AstraZeneca. MedImmune is AstraZeneca’s global biologics research and development arm.
Anifrolumab, formerly known as MEDI-546, blocks the receptor of all major pro-inflammatory type I interferon molecules, including IFN-α, IFN-β, and IFN-ω. These molecules are produced in excess by 60-80% of adult SLE patients and have been implicated as mediators of lupus development.
Results from a Phase 2 trial (NCT01438489) showed that anifrolumab is well-tolerated and reduced disease activity in patients with moderate-to-severe systemic lupus erythematosus (SLE).
To study the medicine in a larger population, MedImmune created the pivotal TULIP program, which comprised two Phase 3 trials — TULIP 1 (NCT02446912) and TULIP 2 (NCT02446899) — testing anifrolumab versus placebo in patients with moderate-to-severe active SLE.
The TULIP 1 study enrolled 460 adult patients who received intravenous anifrolumab — 150 mg or 300 mg — or a placebo every four weeks, for a total of 13 doses. All patients received standard of care treatment during the study period.
TULIP 2 randomized 373 patients to receive 300 mg anifrolumab or a placebo. Patients also had moderate-to-severe active disease and were receiving standard of care treatments.
For both trials, the primary goal is to determine if anifrolumab increases the proportion of patients who achieve an SLE Responder Index of 4 or higher at week 52. This is defined as a reduction in four or more points in the SLEDAI-2K score (a measure of disease activity), no new organs affected since study start, no worsening in disease activity, and no drug discontinuation.
Researchers also are evaluating if anifrolumab decreases the use of oral corticosteroids, improves skin manifestations, and reduces disease-associated flares.
But recent results show that TULIP 1 failed to reach its primary goal, with the proportion of patients achieving an SLE Responder Index of 4 or higher being similar in the anifrolumab and placebo groups.
The company now will conduct a full evaluation of TULIP data when results from TULIP 2 are available later this year. The results will be presented at an upcoming medical meeting.
Besides the Phase 3 TULIP trials, anifrolumab is being evaluated in a Phase 2 trial (NCT02962960), which is testing subcutaneous injections as the delivery method.
Also, a Phase 3 SLE long-term extension trial (NCT02794285) and a Phase 2 trial for lupus nephritis (NCT02547922) are currently recruiting participants.