Novartis provides update on fingolimod Phase III trial in primary progressive MS

The safety results were consistent with the well-characterized safety profile of fingolimod in relapsing MS (RMS).

PPMS is a disorder of the central nervous system (CNS) which affects approximately 10% of the 2.3 million patients diagnosed with MS worldwide. PPMS is a distinct disease form, different from relapsing MS in terms of its basic disease process, near-absence of acute relapses and fewer active MRI lesions.

The severe irreversible damage to the CNS in PPMS is thought to be caused by different pathways leading to loss of nerve cells and a more rapid, continuous loss of function over time which profoundly impacts patients’ lives. Additionally, the disease is typically diagnosed later than other types of MS, when significant damage to the CNS has already occurred.

Despite considerable research and academic focus, there are currently no approved treatments that have been shown to change the course of this debilitating disease and management focuses mainly on the treatment of symptoms.

"We understand this news is very disappointing for those affected by PPMS and involved in its management. While PPMS is a focus of the MS community, relatively little is known about the disease so finding effective treatments remains a challenge. We will actively work with the MS community to review and analyze the INFORMS results to help increase the understanding of this devastating disease," said Vasant Narasimhan, Global Head of Development at Novartis Pharmaceuticals.

"Gilenya (fingolimod) revolutionized the treatment of relapsing MS as the first oral disease-modifying therapy. We remain strongly committed to continuing to research new treatment options for patients with MS and other neurological conditions."

The INFORMS study was based on the knowledge that fingolimod enters the central nervous system (CNS) and can interact with damage-causing cells residing in the CNS. It was hypothesized that this central effect, which is well understood in relapsing forms of MS, would also be relevant in PPMS.

As opposed to the consistently strong efficacy seen in relapsing MS, the results of the INFORMS study seem to suggest that PPMS and relapsing forms of MS have different underlying mechanisms.

Fingolimod, marketed as Gilenya, is approved in the US for first-line treatment of relapsing forms of MS in adults. In the EU, Gilenya is indicated for adult patients with highly active relapsing-remitting MS (RRMS) defined as either high disease activity despite treatment with at least one disease-modifying therapy (DMT), or rapidly evolving severe RRMS.

Gilenya is the only DMT to impact the course of relapsing MS with high efficacy across four key measures of disease activity: relapses, MRI lesions, brain shrinkage (brain volume loss) and disability progression.

The likelihood of achieving ‘no evidence of disease activity’ (NEDA) across four key measures is more than four-times greater in relapsing MS patients treated with Gilenya compared to placebo.

The safety profile of Gilenya in RMS is well understood and based on substantial evidence from three major clinical trials and extensive real-world experience in more than 100,000 patients, with the total patient exposure now at approximately 172,500 patient years.