Switch to Siponimod Safe, Tolerable With No Washout, Study Finds

Amit Bar-Or, MD, FRCPC

Patients with relapsing multiple sclerosis (RMS) looking to switch their disease-modifying therapy (DMT) to siponimod (Mayzent, Novartis) can do so safely and tolerably with no washout period, according to interim results from the ongoing EXCHANGE clinical trial.¹

The findings, presented by Amit Bar-Or, MD, FRCPC, at the 2021 American Academy of Neurology (AAN) Annual Meeting, April 17-22, demonstrate that switching to siponimod from other oral or injectable DMTs, including fingolimod and teriflunomide, is associated with a low rate of treatment-related adverse events (AEs).

Approved in March 2019² for the treatment of RMS, including clinically isolated syndrome, relapsing-remitting MS (RRMS), and active secondary-progressive MS (SPMS), siponimod has demonstrated significant clinical benefit through slowed disability progression and improvements in cognitive processing speed.

The phase 3b EXCHANGE clinical trial (NCT03623243) was launched to better understand the requirements for converting to siponimod. The prospective, open-label, single-arm trial has a target enrollment of 400 patients, 100 of which will be enrolled in a virtual study cohort that includes at-home monitoring via telemedicine. The primary end point is treatment-related AEs over 6 months, with secondary end points of any AE or hospitalization and change in heart rate from baseline to 6 hours post-first dose.

This interim analysis included data from 112 patients age 18 to 65 (median, 45.5 years) with advancing RMS, including RRMS (n=83), SPMS (n=24), and primary progressive MS (n=4), with a median Expanded Disability Status Scale score of 3.5. Notably, 42% of participants had 1 or more relapses in the prior 12-month period. Fingolimod was the most common DMT used followed by glatiramer acetate, dimethyl fumarate, any interferon, and teriflunomide.

Study participants were being treated for at least 3 continuous months with another oral or injectable DMT prior to study enrollment, at which point they underwent conversion to siponimod within 24 hours. Of note, those who were receiving treatment with teriflunomide were required to undergo an 11 to 14-day washout period with cholestyramine or activated charcoal prior to siponimod conversion.

Following conversion to siponimod, 34.8% of patients reported 1 or more treatment-related AEs (95% CI, 26.2-44.5); 4.5% reported 1 or more serious AEs; and 5.4% had 1 or more AE that led to treatment discontinuation. Among those who either completed or discontinued the study (n=74), 40.5% had at least 1 treatment-related AE (95% CI, 29.5-52.6). SAEs reported include asthenia, MS relapse, noncardiac chest pain, pneumonia aspiration, seizure, and tubulointerstitial nephritis. AEs leading to treatment discontinuation included abnormal behavior, cognitive disorder, peripheral edema, fatigue, insomnia, nausea, pain in extremities, tremor, and vomiting. Treatment-related AEs occurring in greater than 5% of patients including gastrointestinal disorders (8.9%); infections (6.3%); and nervous system disorders, including headache and dizziness (15.2%).

Notably, no meaningful reductions in heart rate were observed from baseline to 6-hours post-first dose across the study cohort.

The findings thus far suggest that conversion to siponimod from other oral or injectable DMTs is safe and tolerable. These data will further help characterize important management guidelines for healthcare providers seeking to switch their patients to siponimod from other DMTs.

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REFERENCES

1. Bar-Or A, Weinstock-Guttman B, Mao-Draayer Y, et al. Safety and tolerability of conversion to siponimod in patients with relapsing multiple sclerosis: interim results of the EXCHANGE study. Presented at: 2021 American Academy of Neurology Annual Meeting. April 17-22, 2021; Virtual. Abstract 077.

2. Novartis receives FDA approval for Mayzent (siponimod), the first oral drug to treat secondary progressive MS with active disease. News release. Novartis. March 26, 2019. Accessed March 26, 2019. https://www.novartis.gcs-web.com/Novartis-receives-FDA-approval-for-Mayzent-siponimod-the-first-oral-drug-to-treat-secondary-progressive-MS-with-active-disease.