Data presented at the American Academy of Neurology (AAN) annual meeting add to the accumulating evidence of the positive benefit/risk profile of Gilenia, a potential first-in-class, once-daily oral therapy for relapsing forms of multiple sclerosis (MS).

Data from the two-year Freedoms study showed that Gilenia 0.5 mg reduced annual relapse rates (ARR) by 62 per cent for treatment naïve patients compared to placebo. For patients previously receiving other treatments, the annual relapse rates were reduced by 44 per cent. In addition, at two years Gilenia delayed the progression of disability by 30 per cent for patients on 0.5 mg compared to placebo.

"These findings reinforce the potential for Gilenia to be a breakthrough therapy option for physicians and people with relapsing forms of MS," said Trevor Mundel, Global Head of Development at Novartis Pharma AG. "The data demonstrate the effectiveness of Gilenia irrespective of treatment history, and further support both the sustained efficacy of Gilenia over two years and the potential benefits of switching from interferon beta-1a, a currently approved MS therapy, to Gilenia."

Of the 1153 patients who participated in the one-year Transforms study, 1027 (89 per cent) elected to enter the one-year extension study. Patients in the extension study who also received Gilenia in the core study remained on their original dose (0.5 mg or 1.25 mg), while patients who had received intramuscular interferon beta-1a (Avonex) were randomized to receive Gilenia 0.5 mg or 1.25 mg].

Patients who received Gilenia 0.5 mg for two years experienced a consistently low ARR at year one (0.16) and at year two (0.18). These patients also retained a significant reduction in relapses and MRI brain lesions over two years compared to the group originally randomized to intramuscular interferon beta-1a and later switched to Gilenia.

In the subset of patients who received intramuscular interferon beta-1a during year one and Gilenia 0.5 mg during year two, the annual relapse rate in year two was reduced by 31 per cent and the number of new or newly enlarged T2 lesions in the brain, a marker of disease activity, was reduced by 67 per cent in the second year..

These findings on efficacy are consistent with those of the one-year core TRANSFORMS study demonstrating Gilenia significantly reduced annualized relapse rates by 52 per cent (0.5 mg dose) vs. intramuscular interferon beta-1a.

Additional data presented at AAN showed that patients in the core Transforms study taking Gilenia 0.5 mg had a 71 per cent reduction in relapses resulting in hospitalization, and a 52 per cent reduction in relapses requiring steroid treatment compared with patients taking intramuscular interferon beta-1a.

The safety profile of Gilenia has been well studied in one of the largest-ever phase-III clinical trial programs conducted in MS. The full programme, including completed as well as on-going studies in MS, now has more than 6600 patient years of experience, with some patients now in their sixth year of treatment.

In the Transforms and Freedoms studies the most commonly reported adverse events for both Gilenia and control groups were nasopharyngitis, headache and fatigue. Gilenia-related adverse events included transient, dose-related, generally asymptomatic heart rate reduction and infrequent transient AV conduction block at treatment initiation, mild (1-3 mm Hg) blood pressure increase, macular edema (more common with 1.25 mg than the 0.5 mg target dose), and asymptomatic, reversible elevation of liver enzymes.

The rates of infections overall, including serious infections, were comparable between treatment groups, although a slight increase in lung infections (primarily bronchitis) was seen in patients treated with Gilenia. The number of malignancies reported across the two studies was small with comparable rates between the Gilenia and control groups.

Novartis has submitted the 0.5 mg dose for regulatory approval in the US and EU as results from the studies indicate that this dose has the most favorable benefit/risk profile. Applications for regulatory approval for Gilenia 0.5 mg were submitted to the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in December 2009. In February 2010, the US FDA granted Gilenia priority review status. Since Gilenia involves a new active ingredient (New Molecular Entity), the US FDA has required an Advisory Committee meeting on June 10 and will evaluate the risk management program, which could result in the US FDA extending its review at the end of the designated six-month period in June 2010.

The brand name Gilenia has been provisionally approved by the US FDA for use in connection with the product, but the product itself has not received marketing authorization or NDA approval from any regulatory authorities.