AstraZeneca announced that two key molecules in MedImmune’s Respiratory, Inflammation and Autoimmune (RIA) portfolio mavrilimumab and sifalimumab met their primary endpoints in respective phase II studies, demonstrating further pipeline progress in core therapeutic areas.
Top-line results from the phase IIb study of mavrilimumab, an investigational monoclonal antibody that inhibits a key pathway in the development of rheumatoid arthritis (RA), achieved its primary endpoints. In the Phase llb study of a methotrexate inadequate responder RA population (EARTH EXPLORER-1), 326 patients with moderate and severe RA were treated for six months with either mavrilimumab (low, medium or high dose) or placebo in addition to standard methotrexate background therapy. The co-primary endpoints of the American College of Rheumatology (ACR) response of ACR20 and Disease Activity Score (DAS28) were met with all mavrilimumab doses confirming the efficacy demonstrated in the previous phase IIa study (EARTH).
The high dose was the most effective with an ACR20 response at week 24 of 73.4 per cent vs 24.7 per cent for placebo (p<0.001) and a reduction in mean DAS28 score at day 85 of 1.9 vs -0.68 for placebo (p<0.001). Additionally, all secondary endpoints including ACR50, ACR70 response and DAS28 remission score achieved statistical significance for the high dose.
Mavrilimumab also produced rapid improvement in the multiple symptoms of rheumatoid arthritis and significant improvements in patient reported outcomes including disability, pain and fatigue. The safety findings observed were consistent with those previously reported for the Phase IIa study. The most commonly-reported adverse events (>3 per cent) included headache, nasopharyngitis (common cold), hypertension, bronchitis and worsening of RA.
“Through innovative, novel research, MedImmune has built a diverse emerging pipeline in Respiratory, Inflammation and Autoimmune disease, covering a broad set of patients. We are focused on advancing data and drug discovery to improve treatment options and clinical outcomes for patients,” said Dr. Bahija Jallal, executive vice president, MedImmune. “Compelling Phase II data from two of our molecules - mavrilimumab for rheumatoid arthritis and sifalimumab for systemic lupus - further confirm our commitment to bringing new medicines to patients as quickly as possible.”
MedImmune also announced top-line results from the Phase II study of sifalimumab (MEDI-545), a novel monoclonal antibody being investigated as a treatment for patients with moderate/severe systemic lupus erythematosus (SLE or lupus). The study met its primary endpoint of percentage of subjects that responded by the SLE Responder Index (SRI-4) at Day 365. Clinically important improvements in organ-specific outcome measures (joint, skin) and patient reported outcomes were also observed.
In the study, three doses of sifalimumab were evaluated against placebo when added to stable standard of care therapy in patients with moderately to severely active lupus despite standard of care therapy. In addition to efficacy in the primary endpoint, there is a broad-based body of clinical evidence supporting the efficacy of sifalimumab. The study achieved two secondary endpoints at specific doses improvement in skin (rashes) as measured by CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) and improvement in fatigue. Sifalimumab demonstrated an overall acceptable safety profile, with a numerical increase in the incidence of Herpes Zoster reactivations.
“Patients with lupus have severely limited options for control of their symptoms, as only one new treatment has been approved in more than 50 years,” said Dr. Bing Yao, senior vice president and Head of MedImmune’s Respiratory, Inflammation and Autoimmunity Innovative Medicines Unit. “There is clearly a sense of urgency to deliver new treatments for patients suffering from this debilitating, chronic disease, and we are hopeful that we will be able to offer a new option.”
The company anticipates presenting additional study results for both molecules at a future medical conference later this year. The Phase II programme in lupus with anifrolumab (MEDI-546), which targets the type 1 interferon receptor, is also ongoing.