Novartis has announced that  new long-term data for Gilenya (fingolimod), the only oral therapy approved to treat people with relapsing forms of multiple sclerosis (MS), show a sustained efficacy benefit and a consistent safety profile with up to 4.5 years of continuous treatment. These results, from an extension of the phase III head-to-head TRANSFORMS study, also showed improved efficacy for patients switched to Gilenya from Avonex (interferon-beta-1a IM), a commonly prescribed MS treatment.

These data were presented at the 22nd Annual Meeting of the European Neurological Society (ENS), from June 9-12 2012 at Prague, Czech Republic.

“These data further reinforce our confidence in Gilenya's long-term effectiveness and safety profile. The TRANSFORMS extension study shows that MS patients treated continuously with Gilenya for up to four and a half years demonstrated sustained low levels of clinical and MRI activity,” said Tim Wright, Global Head of Development, Novartis Pharma. “Furthermore, patients who switched to Gilenya from interferon beta-1a IM showed a reduction in relapses and improvements in MRI measures in the extension compared to the core study.”

In the core TRANSFORMS study, Gilenya demonstrated superior efficacy to interferon-beta- 1a IM, reducing the annualized relapse rate (ARR) by 52 per cent at one year (Gilenya 0.5 mg, ARR = 0.16; interferon-beta- 1a IM, ARR = 0.33; p<0.001). The extension study showed that this low relapse rate was sustained in patients receiving continuous treatment with Gilenya (n=356) for up to 4.5 years (Gilenya 0.5 mg, ARR core study = 0.16; ARR extension study = 0.16). The data from the extension study also showed that patients treated with Gilenya continuously maintained a low brain atrophy rate throughout the study as measured by assessing brain volume loss, which is valued as a predictor of long-term disability.

For patients who switched to Gilenya for the open-label extension study (n=167), their ARR was 0.33 in the core study when treated with interferon-beta-1a IM and 0.20 in the extension phase when treated with Gilenya (n.s.). Patients in the switch group also displayed a slowing of brain atrophy following the switch to Gilenya.

These extension data from up to 4.5 years also showed long-term treatment with Gilenya was generally well tolerated with a safety profile consistent with pivotal trials. In line with previous studies, including the core TRANSFORMS study, the most common adverse events were nasopharyngitis, headache, and upper respiratory tract infections. Switching therapy from IFN beta-1a to Gilenya did not reveal any new or unexpected safety concerns. On treatment initiation, a low incidence of asymptomatic transient bradycardia was observed in patients who switched from interferon-beta-1a IM to Gilenya (IFN-0.5 mg [0.6 per cent]), which resolved without treatment. Overall cardiac events were similar across all patient groups.

In addition, all patients treated with Gilenya in the extension phase, regardless of original treatment in the core study, showed comparable percentage of patients free from MRI disease activity by the end of the study. (Free from Gd enhanced T1 lesions: 77.4 per cent in switch group vs. 74.7 per cent Gilenya 0.5mg; Free from new/newly enlarged T2 lesions: 45.0 per cent in switch group vs. 42.0 per cent Gilenya 0.5mg). The continuous and switch groups did not significantly differ with respect to disability progression at the end of the study.

“This extension study data provide deeper insight into the efficacy and safety profile of fingolimod,” said Dr Xavier Montalban, director of the Multiple Sclerosis Centre of Catalonia and of the Unit of Clinical Neuroimmunology, Vall d'Hebron University Hospital, Barcelona, Spain. “The results, which are consistent with the pivotal phase III studies, confirm that fingolimod is highly effective in treating relapsing forms of MS, and as the first available oral MS treatment, continues to be a valuable treatment option for appropriate patients.”

TRANSFORMS was a large phase III double-blind, double-dummy, head-to-head study that involved 1,292 patients with relapsing-remitting MS that was conducted over one year, comparing the efficacy and safety of Gilenya to interferon-beta-1a IM. At the end of the 12-month core study, eligible patients could enroll in the extension study, which ran for an additional 3.5 years. Patients on once-daily oral Gilenya remained on drug and those who had been treated with interferon-beta-1a (IM) switched to Gilenya for the duration of the extension study.

As of February 2012, approximately 36,000 patients have been treated with fingolimod in clinical trials and in the post-marketing setting, some up to seven years, and currently there is approximately 34,000 patient years of exposure.

Gilenya, licensed from Mitsubishi Tanabe Pharma Corporation, is the first in a new class of compounds called sphingosine 1-phosphate receptor (S1PR) modulators. It has demonstrated superior efficacy compared to Avonex, a commonly prescribed treatment, showing a 52 per cent relative reduction in annualized relapse rate (primary endpoint) and a 40 per cent relative reduction in the rate of brain atrophy (secondary endpoint) at one year in a pivotal head-to-head trial in patients with relapsing-remitting multiple sclerosis. In a recent sub-analysis, Gilenya showed a 61 per cent relative reduction in annualized relapse rate compared to interferon-beta-1a (IM) at one year in subgroups of patients with highly active relapsing-remitting MS not responding to interferon treatment.

Gilenya is generally a highly effective once-daily oral MS treatment. In clinical trials it was generally well tolerated with a manageable safety profile, and there is increasing experience of Gilenya's long-term effectiveness and safety profile, with approximately 36,000 patients having been treated in clinical trials and in a post-marketing setting. Currently, there is approximately 34,000 patient years of exposure. In clinical trials, the most common side effects were headache, liver enzyme elevations, influenza, diarrhoea, back pain, and cough. Other Gilenya-related side effects included transient, generally asymptomatic, heart rate reduction and atrioventricular block upon treatment initiation, mild blood pressure increase, macular edema, and mild bronchoconstriction.

The rates of infections overall, including serious infections, were comparable among treatment groups, although a slight increase in lower respiratory tract infections (primarily bronchitis) was seen in patients treated with Gilenya. The number of malignancies reported across the clinical trial program was small, with comparable rates between the Gilenya and control groups.

Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. It offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products.