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Autoimmune diseases: Mavrilimumab in rheumatoid arthritis and Sifalimumab in systemic lupus erythematosus both met primary endpoints


Mavrilimumab and Sifalimumab have met their primary endpoints in respective phase II studies, demonstrating further pipeline progress in core therapeutic areas.

Mavrilimumab, an investigational monoclonal antibody, has achieved its primary endpoints. In the phase llb study of a Methotrexate inadequate responder rheumatoid arthritis population ( EARTH EXPLORER-1 ), 326 patients with moderate and severe rheumatoid arthritis 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% vs 24.7% for placebo ( p less than 0.001 ) and a reduction in mean DAS28 score at day 85 of -1.9 vs -0.68 for placebo ( p less than 0.001 ).
Additionally, all secondary endpoints including ACR50, ACR70 response and DAS28 remission score achieved statistical significance for the high dose.
Mavrilimumab has 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 ( greater than 3% ) have included headache, nasopharyngitis, hypertension, bronchitis and worsening of rheumatoid arthritis.

Mavrilimumab is a first in class human monoclonal antibody that targets the alpha receptor for the cytokine granulocyte-macrophage colony-stimulating factor ( GM-CSF ). Through the targeted blockade of the receptor on the macrophage, a key cell in the pathogenesis of rheumatoid arthritis, mavrilimumab could add a significant new treatment option for rheumatoid arthritis patients.

A phase II study of Sifalimumab, a novel monoclonal antibody being investigated as a treatment for patients with moderate / severe systemic lupus erythematosus ( SLE or lupus ), has 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 has demonstrated an overall acceptable safety profile, with a numerical increase in the incidence of herpes zoster reactivations.

Sifalimumab is a human monoclonal antibody that targets IFN-alpha, a type of inflammatory cytokine in the body known to play a role in the development of systemic lupus erythematosus.
Previous studies have shown that high levels of type I IFN-alpha are correlated with more severe disease activity in SLE patients, and early studies of Sifalimumab have demonstrated that this agent blocks signaling of all interferon alpha subtypes. ( Xagena )

Source: AstraZeneca, 2014

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