Long-term study finds MS disease activity stayed low for up to 13 years

Treatment with Ponvory (ponesimod) for up to 13 years was associated with sustained low disease activity in adults with relapsing-remitting multiple sclerosis (RRMS), with relapse rates and brain lesion activity decreasing over time.

That’s according to new data from a completed Phase 2b clinical trial (NCT01006265) and its long-term extension study (NCT01093326). The researchers also reported no new safety concerns with treatment lasting up to 13 years.

The results were described in the study, “Long-term safety and efficacy of ponesimod, an oral S1P1 receptor modulator, in relapsing-remitting multiple sclerosis (RRMS): Results from randomized phase 2b core and extension studies spanning up to 13 years,” published in Multiple Sclerosis and Related Disorders.

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Ponvory is an oral disease-modifying therapy (DMT) approved in the U.S. for adults with relapsing forms of multiple sclerosis (MS). It works by “trapping” certain immune cells in the lymph nodes, preventing them from reaching the brain and spinal cord, where they can contribute to MS-driving inflammation.

Ponvory’s approval was primarily supported by findings from the Phase 3 OPTIMUM trial (NCT02425644), which showed that 20 mg Ponvory outperformed Aubagio (teriflunomide) at lowering relapse rates, reducing evidence of brain damage, and easing fatigue over two years of treatment.

The 20 mg dose was selected based in part on findings from a previous Phase 2b study, which compared daily doses of 10, 20, and 40 mg with a placebo over about six months. Participants who completed the 24-week core study could enter a long-term extension with three treatment periods.

Initially, patients received 10, 20, or 40 mg of Ponvory. The 40 mg dose was discontinued after the first treatment period because of poor tolerability. The 10 mg dose was later discontinued after an interim analysis supported 20 mg as the preferred dose, and all participants received 20 mg during the final treatment period.

Researchers have now reported data covering up to 13 years of Ponvory treatment. Of the 393 participants who completed the core study, 90% entered the long-term extension and about 42% ultimately completed the final treatment period. The current analysis focused on the 20 mg dose group because 20 mg is Ponvory’s approved maintenance dose and was the dose given to all participants during the final treatment period.

In the 20 mg dose group, the estimated annualized relapse rate was 0.142 confirmed relapses per year across the full analysis period. The rate decreased between the first and second years of treatment and showed a generally declining trend over time.

Relapse and disability rates remained low with long-term treatment

During follow-up, 39.3% of participants in the 20 mg group experienced a confirmed relapse and 20% experienced 24-week confirmed disability accumulation. Kaplan-Meier analyses estimated that by about 13 years, 52.5% of participants would have experienced a confirmed relapse and 31.3% would have experienced 24-week confirmed disability accumulation.

Disability scores, however, remained generally stable throughout the study, with no clinically meaningful change from baseline. Brain lesions showing active inflammation decreased substantially, from a mean of 2.62 at treatment initiation to 0.26 after 12.4 years. New or enlarging brain lesions also decreased from a mean of 0.66 during the first 48 weeks of treatment to 0.10 after 12-13 years.

“These findings reinforce the long-term efficacy of [Ponvory] in controlling disease activity, supporting evidence for sustained benefit of long-term [Ponvory] treatment in managing RRMS,” the researchers wrote.

The long-term safety profile of Ponvory remained generally consistent with earlier findings. In the 20 mg group, 92.4% of participants experienced at least one treatment-emergent adverse event, most of which (73.1%) were mild or moderate in severity. Still, 13.1% discontinued Ponvory because of treatment-emergent adverse events. One participant in the 20 mg group died from a cardiovascular event, which was considered unrelated to treatment.

Overall, Ponvory “treatment for up to 13 years in participants with RRMS showed no new safety concerns, and participants experienced low disease activity across relevant clinical and MRI outcomes,” the researchers concluded.