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Anifrolumab approved by FDA for systemic lupus erythematosus

The interferon antagonist anifrolumab has been cleared for the treatment of adults with moderate-to-severe systemic lupus erythematosus by the FDA.

Systemic lupus erythematosus (SLE) is a rare, chronic autoimmune disease which affects approximately six-times more women than men. It is the most common form of lupus, accounting for approximately 70% of all cases. There is a wide geographical variation in the incidence of SLE and has been found to vary between 23.2 cases per 100,000 in North America to 0.3 cases per 100,000 in Africa and the Ukraine. Other estimates suggest a general prevalence of approximately 1 to 10 per 100,000 person-years.

SLE is a systemic illness affecting many different organ systems including the skin, with a typical butterfly rash across the cheeks, the musculoskeletal system, producing arthritis and myositis, and constitutional symptoms such as fatigue, fever and weight loss. The cause of SLE remains unclear but the condition is characterised by the presence of autoantibodies and guidance from EULAR in 2019 has suggested treatment with hydroxychloroquine, glucocorticoids, immunosuppressants and biologics, in particular, belimumab. However, it has been shown that in patients with SLE, there is excessive production of type 1 interferon (IFN) and in particular, INF-alpha. Blockage of type 1 IFN could therefore represent a potential therapeutic modality for SLE.

Cell signalling in SLE occurs via activation of the IFN pathway mediated via the type 1 IFN receptor. Moreover, blockage of this IFN pathway may reverse immune dysregulation and the tissue damage seen in SLE. Anifrolumab binds to the IFN receptor and therefore potentially reduces some of the immune dysregulation seen in SLE.

The FDA based its approval of anifrolumab on the results of three separate trials. The first in 2016, undertaken in 305 patients, showed that treatment with intravenous anifrolumab (300mg or 1000mg) every 4 weeks for 48 weeks led to a substantial reduction in disease activity in patients with moderate-to-severe SLE. Further studies included TULIP-1 and TULIP-2, both of which were Phase III trials. The primary endpoint was the rate of British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA), which is a validated global measure of treatment response among those with SLE. Interestingly, anifrolumab failed to reach the BICLA endpoint in TULIP-1 (37% vs 27%, anifrolumab vs placebo) when added to standard therapy. In contrast, significantly more patients assigned to anifrolumab than placebo, achieved the primary endpoint in TULIP-2, (47.8% vs 31.5%, anifrolumab vs placebo, p = 0.001).

An ongoing clinical trial in approximately 360 participants with moderate-to-severe SLE, is currently assessing the efficacy and safety of a subcutaneous form of anifrolumab in adults receiving standard therapy, over a 52-week period.

Anifrolumab is under regulatory review in both the EU and Japan.

Source. AstraZeneca August 2021