Anifrolumab met primary and secondary endpoints in Phase II, significantly reducing lupus disease activity compared with placebo across multiple endpoints
Data highlight promise of blocking the interferon pathway
Data will be presented at an oral session on Tuesday, 10 November at 16:30 Pacific Time
10 November 2015
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.
NOTES TO EDITORS
Anifrolumab (formerly MEDI-546) is an investigational, fully human monoclonal antibody that binds to subunit 1 of the Type I IFN receptor, inhibiting the activity of all Type I IFNs including IFN-α, IFN-β and IFN-ω. Anifrolumab is the only anti-type-I IFN receptor approach currently in development for SLE. Anifrolumab is currently in Phase III development for SLE, with a Phase II trial in lupus nephritis and Phase I subcutaneous administration study anticipated to begin in the second half of 2015.
About the Phase II Anifrolumab Trial
The efficacy and safety of anifrolumab was evaluated in a Phase II, randomized, double-blind, placebo-controlled trial in which 305 adults with seropositive moderate to severe SLE taking standard of care medication were randomized to receive intravenous (IV) anifrolumab 300mg or 1000mg Q4W or placebo (PBO) every four weeks for 48 weeks. Patients were stratified by SLEDAI score, OCS dose, and IFN gene signature (IFN high vs. IFN low) based on a 4-gene expression assay.
The SLE Responder Index is recognised by health authorities and combines criteria from three internationally validated disease activity measures, representing a clinically significant improvement in lupus disease activity. To achieve SRI4 response, an individual with lupus must have at least a 4-point improvement on the SLE Disease Activity-2K (SLEDAI-2K) score and have no worsening on the Physician Global Assessment of disease activity and the BILAG (British Isles Lupus Assessment Group) disease activity index. Disease activity was also assessed by Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), BICLA, and 28-joint count.
Additional Detail on Trial Results
Primary Endpoint: SRI response with sustained reduction of OCS at day 169: PBO: 17.6%; 300 mg: 34.3%, odds ratio (90% CI): 2.38 (1.33, 4.26), p=0.014; 1,000 mg: 28.8%, OR): 1.94 (1.08, 3.49), p=0.063
Secondary Endpoints: 1) SRI response with sustained reduction of OCS at day 365: (PBO: 25.5%; 300 mg: 51.5%, OR: 3.08 (1.86, 5.09); p ‹0.001; 1,000 mg: 38.5%, OR: 1.84 (1.11. 3.04), p=0.048; 2) Reduction of OCS to ≤7.5 mg/day by day 365 in those patients receiving ≥10 mg/day of OCS at baseline: PBO: 26.6%; 300 mg: 56.4%, OR: 3.59 (1.87, 6.89), p=0.001; 1,000 mg 31.7%, OR: 1.23 (0.64, 2.37), p=0.595
Interferon Gene Signature High Subgroup:
SRI response with sustained reduction of OCS at day 169: PBO: 13.2%; 300 mg: 36.0%, OR: 3.55 (1.72, 7.32); p=0.004; 1,000 mg: 28.2%, OR: 2.65 (1.27, 5.53); p=0.029.
Full data abstract can be viewed here:
About the Phase III TULIP Programme
The TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) programme includes two Phase III clinical trials that will evaluate the efficacy and safety of anifrolumab versus placebo in patients with moderately to severely active, autoantibody-positive SLE, while receiving standard of care treatment. The programme will assess the effect of anifrolumab in reducing disease activity (as measured by the SRI), decreasing use of OCS, improving skin manifestations (as measured by CLASI) and reducing flares.
About Systemic Lupus Erythematosus (SLE)
Systemic lupus erythematosus (SLE), or lupus, is an autoimmune disease in which the immune system produces antibodies that, instead of targeting viruses or other foreign invaders, attack healthy tissue in the body, including skin, joints, the brain and blood vessels. SLE can cause a range of symptoms, including pain, rashes, fatigue, swelling in joints, and fevers. It is associated with a greater risk of death from causes such as infection and cardiovascular disease.
MedImmune is the worldwide biologics research and development arm of AstraZeneca. MedImmune is pioneering innovative research and exploring new pathways across key therapeutic areas, including respiratory, inflammation and autoimmunity; cardiovascular and metabolic disease; oncology; neuroscience; and infection and vaccines. The MedImmune headquarters is located in Gaithersburg, Md., one of AstraZeneca’s three global R&D centres. For more information, please visit www.medimmune.com.
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com.
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