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Rituxan, the blockbuster drug from Genentech and Biogen Idec, is the latest casualty in the systemic lupus erythematosus indication, reaffirming the complexity of this disease. In a Phase II/III trial, it was unable to demonstrate clinical efficacy in patients with SLE. Although Datamonitor believes that Rituxan will continue to be used off-label, these results make approval much more difficult.
Systemic lupus erythematosus (SLE) is a chronic, life-long and potentially fatal autoimmune disease, characterized by multiple organ system distress and unpredictable flares. Despite the disease's severity, there has not been a product approved in the US for SLE for nearly 40 years. Current treatment of SLE is largely limited to off-label therapies, many of which have serious side effects. One such therapy used off-label for severe SLE is Rituxan (rituximab), from Genentech and Biogen Idec (marketed outside of the US as MabThera, by Roche). Rituxan is an anti-CD20 monoclonal antibody which is approved for the treatment of non-Hodgkin's lymphoma and moderately to severely active rheumatoid arthritis. According to Datamonitor's report 'Stakeholder Opinions: Systemic Lupus Erythematosus', between 1% and 10% of SLE patients receive Rituxan off-label, generating up to $650m in sales across the seven major markets.
The EXPLORER trial was a randomized, double-blind, placebo-controlled, multi-center study, designed to evaluate the efficacy and safety profile of Rituxan in 257 patients with moderate-to-severe SLE while receiving immunosuppressant over 52 weeks. The primary endpoint was the proportion of Rituxan treated patients who achieved a major clinical response (MCR) or partial clinical response (PCR) measured by the BILAG activity index, which evaluates patients based on the need for additional treatment. Less than two weeks after Rituxan failed its trial for primary progressive multiple sclerosis, Genentech reported a failure for SLE.
Although Rituxan failed in the EXPLORER trial, Genentech will derive hope of positive news from the LUNAR trial, which is investigating the therapy in patients with lupus nephritis. This is a more homogenous patient population, in which the disease specifically affects the kidney. Datamonitor expects Rituxan will fare better in lupus nephritis than in SLE. The results of the LUNAR study should be announced in the first quarter of 2009, and are hotly anticipated by all lupus stakeholders.
Despite this, the FDA requires two positive trials for approval. Although Genentech may try to push the FDA for approval off the back of positive LUNAR data, it is likely that the company will be required to conduct a further trial. A distinct approval pathway may emerge through an advisory committee.
Regardless of this recent failure, physicians will continue to prescribe Rituxan off-label. The failure of the drug in the EXPLORER trial has opened up the door for competition from LymphoStat-B (belimumab), the promising late-stage product from HGS/GlaxoSmithKline. However, although LymphoStat-B could prosper from negative Rituxan news, and the race for first-to-market is indeed blown wide open, Datamonitor remains confident that Rituxan is the more likely winner.
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