The investigatory therapy for secondary progressive MS returned even more promising post hoc analysis prior to its FDA consideration.
Bruce Cree, MD, PhD, MAS
New analysis from a phase 3 trial reports that oral, once-daily siponimod (BAF312) consistently reduced disability progression in patients with secondary progressive multiple sclerosis (SPMS).
Post-hoc analysis details from Novartis’ EXPAND study — presented Friday at the 70th annual meeting of the American Academy of Neurology in Los Angeles, CA — have lead researchers to believe the therapy that such risk reduction with siponimod is substantially disassociated from MS relapse.
Siponimod is a selective modulator of sphingosine-1-phosphate (S1P) receptor subtypes. It functions by binding to the S1P1 sub-receptor on lymphocytes, preventing them from entering the central nervous system (CNS). The therapy also has the capability to enter the CNS and modulate damaging cell activity, giving it the potential to treat neurological function loss in patients with MS.
The randomized, double-blind, placebo-controlled phase 3 trial to compare the efficacy and safety of siponimod versus placebo in people with SPMS was the largest of its kind to investigate a therapy for SPMS, with 1,651 participants enrolled from 31 countries. On average, patients were 48 years old, had been living with MS for about 17 years, and had been demonstrating disability progression in the 2 years prior to the study start. They also reported an Expanded Disability Status Score (EDSS) between 3.0-6.5, indicating the use of a unilateral walking aid.
Researchers randomized patients 2:1 to receive either 2 mg siponimod once-daily or placebo, with patients continued on the investigate therapy in an open-label extension following the study’s end.
Patients treated with siponimod reported a statistically significant reduction in disability progression risk, sustained for both 3 and 6 months. Using a model-based approach in the new analyses, researchers found the estimated risk reduction for disability progression sustained at 3 months ranged from 14-20% compared to placebo for non-relapsing patients. The estimated risk reduction at 6 months grew to 29-33%.
The therapy’s effect on cognition was also a noted benefit in post hoc analysis. Evaluating via the Symbol Digit Modalities Test (SDMT), patients treated with siponimod showed a significant improvement in cognitive processing speed from baseline to month 24, compared to placebo, in all patients (P = 0.0004), as well as those who had suffered relapses within 2 years before the trial’s stat (P = 0.0151).
As MS currently affects more than 2 million people, its secondary progressive form is characterized by an even greater loss of neurological function and physical capability over time. Siponimod’s ability to treat symptoms evident in about half of all MS patients means it could have a true impact on patients’ daily lives, Danny Bar-Zohar, global head of Novartis’ Neuroscience Department, said in a statement.
“Furthermore, the advanced models used in the new analyses help us to better understand the relationship between relapses and disability and the effect of siponimod on these parameters,” Bar-Zohar said. “We are encouraged by these latest findings, which further solidify the clinical evidence for siponimod as a potential new, much needed treatment option for SPMS."
EXPAND study steering committee member Bruce Cree, MD, PhD, MAS, clinical research director and associate professor at the University of California, San Francisco, School of Medicine, added that there’s a gap in treating the inflammatory-neurological duality of SPMS that siponimod has clearly shown being able to fill.
"Siponimod's beneficial effect on preventing disability progression, independent from its reduction in relapse frequency, demonstrates that patients with secondary progressive MS could benefit from this treatment,” Cree said.
Novartis has begun the submission process with the US Food and Drug Administration to have siponimod indicated for patients with SPMS in the first half of 2018.
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