Novartis yesterday said that its investigational oral multiple sclerosis drug, fingolimod, has shown long-term efficacy in patients with the relapsing-remitting form of the disease in a Phase II study. Of particular note, says the company, is that a number of patients experienced a more than 50% reduction in their annual relapse rate that was maintained over the 18-month course of the study. Currently marketed therapies convey an average reduction in relapse rates of just 30% in two-year studies, Novartis points out, with frequent injections ranging from once-daily to 3-6 times weekly.
The Phase II study – conducted at 32 centres across 11 countries in Europe and Canada – randomised 281 patients to receive one of two doses of fingolimod or placebo for a six-month period and measured disease activity via magnetic resonance imaging and clinical relapse incidence. After six months, patients could opt to enter an extension phase, whereby placebo receivers were re-randomised to get either the 1.25mg or 5mg dose of fingolimod. Both doses were equally effective - although because the higher dose was linked to a greater incidence of side effects (primarily colds, influenza and headache), all patients are now being given the 1.25mg dose – with results showing that the “vast majority” of patients were free from lesions showing active inflammation at month 18. Analysis of the two-year data for fingolimod will be presented at a key medical congress in the second half of this year.
Fingolimod, also code-named FTY720, is an oral therapy licensed from Mitsubishi Pharma that binds to the sphingosine 1-phosphate receptor 1 (S1P1) on circulating lymphocytes and traps them within the lymph system, thus cutting the levels of activated T cells in the bloodstream and central nervous system. It is the action of a raised inflammatory response involving activated T cells that is the root cause of multiple sclerosis, where the body attacks its own nervous system. Over time, the transmission of electrical nerve impulses is disrupted, nerve cells are destroyed and patients experience symptoms ranging from fatigue, tingling and numbness to poor muscle control and paralysis.
“Oral fingolimod has a novel mode of action different from all available multiple sclerosis therapies,” says Novartis, adding: “If the Phase III clinical programme confirms the promise of the Phase II results oral fingolimod could represent a major improvement in the way MS will be treated in the future.” More than 2 million people worldwide are believed to suffer from MS and the marketplace has proved to be a highly lucrative one for the pharmaceutical industry. And, with no oral therapies currently available, the race is on to secure what could be a very large slice of the pie. Biogen Idec – one of the big players and manufacturer of Avonex (interferon beta 1a) and Tysabri (natalizumab) – has BG-12, an oral fumarate, in Phase II with partner Fumapharm AG, while Serono, GlaxoSmithKline and Sanofi-Aventis are also chasing the rabbit. However, Teva was recently forced to drop development of its oral version of Copaxone (glatiramer acetate) after it failed to show an acceptable level of efficacy.
However it plays out, the first company to bring an oral MS drug to market is almost certain to have a billion dollar-plus product on its hands, according to Datamonitor, which has predicted that oral products will lead to a doubling of the market for MS treatments, reaching $6 billion a year in 2012.