AstraZeneca, along with its global biologics research and development arm, MedImmune, will present positive data today from the Phase II trial of anifrolumab for the treatment of moderate-to-severe systemic lupus erythematosus (SLE or lupus) at the American College of Rheumatology (ACR) 2015 Annual Scientific Meeting in San Francisco. Trial results demonstrated that anifrolumab significantly reduced disease activity as measured by several SLE composite endpoints and improved symptoms of lupus such as rash and arthritis.
Anifrolumab is a new monoclonal antibody against the type I interferon (IFN) receptor that inhibits the activity of all type I IFNs, which play a central role in lupus. The trial met its primary endpoint of difference in the percentage of patients who achieved response as measured by the SLE Responder Index 4 (SRI4) at day 169, along with a sustained reduction of oral corticosteroid (OCS) use between day 85 and day 169. Responses occurred for 34.4 percent of patients receiving anifrolumab 300mg IV and for 28.8 percent of patients receiving anifrolumab 1,000mg IV every four weeks versus 17.6 percent of patients receiving placebo.
The trial also met both secondary efficacy endpoints measuring responses at day 365, with even greater effect. Over 50 percent (51.5) of patients receiving anifrolumab 300mg and 38.5 percent of patients receiving anifrolumab 1,000mg achieved SRI4 response at day 365 with sustained reduction of OCS, compared with 25.5 percent of patients receiving placebo. The trial also met its other secondary endpoint of a reduction of OCS use to ≤7.5 mg/day by day 365 in those patients taking ≥10 mg/day of OCS at baseline.
Principal Investigator Richard A. Furie, MD, Chief, Division of Rheumatology, North Shore-LIJ Health System, said: "The lupus community has been disappointed too often with clinical trial results. We have been eagerly awaiting clinical data of this magnitude for many years. These results provide very compelling evidence that blocking the type 1 interferon system with an inhibitor of the type I interferon receptor is a promising strategy for the treatment of SLE and support the progression of anifrolumab into Phase III."
Bing Yao, Senior Vice President, Research and Development for Respiratory, Inflammation & Autoimmunity, MedImmune, said: "These positive results for anifrolumab represent real hope for patients with lupus, who have only seen one new treatment for their disease in almost 60 years. We followed the science behind the potential therapeutic benefits of blocking the interferon pathway and look forward to confirming the data in our robust Phase III TULIP programme, as we seek to bring a new medicine for people with lupus."
Adverse events (AEs) were similar across groups. Serious adverse events were reported in 18.8 percent of patients receiving placebo and 16.7 percent of patients in the pooled anifrolumab groups. A dosage-dependent increase in Herpes zoster (Placebo: 2.0%; 300mg: 5.1%; 1000mg: 9.5%) cases and a greater number of influenza infections (most unconfirmed) (placebo: 2.0%; 300mg: 6.1%; 1,000mg: 7.6%) were observed for patients receiving anifrolumab.
Greater efficacy was observed in a pre-defined subgroup of patients with elevated interferon (IFN) gene signature at baseline. Anifrolumab is being developed with an IFN gene signature test designed to identify patients who may be more likely to benefit from treatment.
A consistent benefit was also observed with anifrolumab over placebo in other clinically- important measures, including reduction in disease activity based on the BILAG-based Combined Lupus Assessment (BICLA), improvement in skin rashes and reductions in the numbers of swollen and tender joints.
The US Food and Drug Administration recently assigned anifrolumab Fast Track designation, which facilitates the development and expedites the review process of medicine candidates that treat serious conditions and fill an unmet medical need. The anifrolumab Phase III programme was initiated in July.