AstraZeneca sets stage for marketing application with promising pivotal lupus drug data
After fumbling in its first late-stage lupus study, AstraZeneca disclosed that a second pivotal trial testing its experimental drug, anifrolumab, had met the main goal, in August. Earlier this week, the British drugmaker broke out the numbers from its successful study.
Last year, anifrolumab failed to meet the main goal of diminishing disease activity in the 460-patient TULIP I study, a 52-week trial that tested two doses of the drug versus a placebo. But in the 373-patient TULIP II study, the higher dose (300 mg) was compared to patients given a placebo — patients in both arms were on baseline standard care.
Anifrolumab induced a statistically significant improvement with 47.8% of patients responding to the drug, versus 31.5% of patients on placebo at week 52, as measured by the British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) composite measure — which requires improvement in all organs with disease activity at baseline with no new flares.
The AstraZeneca drug also proved statistically superior on a raft of secondary endpoints, such as its impact on oral corticosteroid (OCS) use and skin manifestations. 51.5% of patients taking OCS achieved a sustained reduction in OCS use, versus 30.2% of patients on placebo; and 49% of patients receiving anifrolumab with moderate-to-severe skin disease saw improvements at week 12, compared with 25% of patients receiving placebo.
Lupus is a drug developer’s nightmare. In the last six decades, there has been one FDA approval. In recent years, the field has resembled a graveyard. Last October, UCB and Biogen’s anti-CD40L drug failed in a late-stage study, months after Xencor and Sanofi’s Ablynx also conceded defeat in their programs.
Meanwhile, there is cause for some cautious optimism, with a cadre of drug developers working on developing new treatments. Some biologics that are approved for other autoimmune diseases are being tested for use in lupus — including Eli Lilly’s Olumiant and J&J’s Stelara. French biotech Neovacs is also in mid-stage development with a lupus vaccine.
The only biologic so far to win approval for lupus is GSK’s Benlysta — which was cleared for adult use in 2011 and for rare cases of childhood lupus this year. (GSK is in the midst of testing Benlysta in combination with Roche’s rituximab in the hope the combination will have a more potent effect on the disease versus Benlysta monotherapy.)
Apart from that, patients are usually given NSAIDS, antimalarial drugs, corticosteroids, and immunosuppressants to control the symptoms of the systemic autoimmune disease, in which the body’s immune system launches an attack on its own tissues and organs. About 1.5 million Americans and at least five million people globally suffer from a form of lupus, estimates The Lupus Foundation of America.
Anifrolumab, which is also being evaluated in a mid-stage trial in lupus nephritis, is a monoclonal antibody engineered to thwart the activity of all type I interferons — cytokines involved in inflammatory pathways. Roughly 60% to 80% of adults with systemic lupus erythematosus (SLE) carry increased type I interferon gene signature, according to AstraZeneca.
Despite the failed TULIP 1 trial, AstraZeneca’s Mene Pangalos in August said the company is exploring pathways to get anifrolumab on the market. “There is now a strong body of evidence demonstrating the benefit of anifrolumab, and we look forward to bringing this potential new medicine to patients with systemic lupus erythematosus as soon as possible,” he said in a statement on Monday.