#MSVirtual2020 – Ponesimod Superior to Aubagio in Delaying Disability Progression in Relapsing MS, Trial Data Show

Janssen Pharmaceuticals’ investigational oral therapy ponesimod is superior to Sanofi’s Aubagio (teriflunomide) in delaying disability progression in adults with relapsing multiple sclerosis (MS), according to exploratory analyses of OPTIMUM clinical trial data.

These and other findings from Janssen’s MS research program, including on the health and economic burden of fatigue in relapsing MS patients in the U.S, will be presented through 13 company-sponsored posters during MSVirtual2020 Sept. 11–13.

MSVirtual2020 will be the 8th joint meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

“We are delighted to present our latest MS research highlighting disease insights and the encouraging efficacy and safety of our investigational RMS [relapsing MS] therapy, ponesimod, at MSVirtual2020,” Bill Martin, PhD, global therapeutic head of neuroscience at Janssen Research & Development, said in a press release.

Ponesimod, developed by Actelion (owned by Janssen), is currently under regulatory review in the U.S. and European Union as a potential oral treatment for adults with relapsing MS.

The global OPTIMUM Phase 3 study (NCT02425644) compared the safety and effectiveness of ponesimod versus Aubagio, an approved first-line oral MS treatment, in 1,133 adults with relapsing-remitting MS (RRMS) and active secondary progressive MS.

While both Aubagio and ponesimod limit the circulating number of immune cells involved in MS, Aubagio does so by preventing their proliferation and ponesimod does it by “trapping” them in lymph nodes.

Participants were assigned randomly to receive either a 20 mg tablet of ponesimod (567 patients) or a 14 mg tablet of Aubagio (566 patients), once a day for 108 weeks (about two years). A total of 86.9% of participants completed the study.

OPTIMUM top-line data showed that ponesimod was significantly superior to Aubagio at dropping annual relapse rates (by 30.5%) and the number of new, active, brain lesions (by 56%).

Ponesimod also outperformed Aubagio in relieving fatigue, as reported by patients through a MS-specific new tool — the Fatigue Symptoms and Impacts Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS).

Now, results from OPTIMUM exploratory analysis on disability progression will be presented in the poster “Effect on Disability Measures and Multiple Sclerosis Functional Composite (MSFC) in Patients with Relapsing Multiple Sclerosis from the Phase 3 Ponesimod Versus Teriflunomide OPTIMUM Study” (abstract #P0204).

Researchers assessed participants’ impairment and disability progression through changes in several functional measures — including the timed 25-foot walk, 9-hole peg test, symbol digit modalities test, paced auditory serial addition test, and expanded disability status scale — and composites, or combinations, of such measures.

Results showed that ponesimod was more effective than Aubagio in delaying disability progression in the overall population. In addition, a smaller proportion of ponesimod-treated patients experienced disability events, compared with those given Aubagio.

Notably, these differences more often were statistically significant when analyzing composite measures, since they provide “more power to statistical assessments owing to greater number of events analyzed, making them particularly useful in [relapsing] MS trials,” the researchers wrote.

In the poster, “A Real-World Study Characterizing Symptoms and Impacts of Fatigue in U.S. Adults with Relapsing Multiple Sclerosis Using a Novel Disease Specific Scale,” (abstract #P1004) researchers will present data on the impact of fatigue — one of the most frequent and disabling symptoms in MS — in patients in the U.S. using the FSIQ-RMS.

The results were part of an ongoing non-interventional prospective study of adults with relapsing forms of MS who are able to walk and recruited across the U.S. via an online survey.

A total of 142 patients, with a mean age of 43.5 years, completed demographic and clinical questionnaires, including the FSIQ-RMS, administered daily for seven days, via an online patient platform called Carenity.

The FSIQ-RMS measures fatigue symptoms, their severity, and corresponding impacts on physical, cognitive/emotional, and coping domains.

Results showed that most patients reported severe fatigue, and that more than half (56%) experienced fatigue before being diagnosed with MS. In addition, patients currently relapsing showed higher levels of fatigue symptoms than those who were not, and heat exposure (82%) was the most commonly reported triggering factor for fatigue.

Fatigue was reported to have a high impact on patients’ daily life, particularly in those with lower disability.

In another poster, “Comorbidity and Economic Burdens of Fatigue Among Patients with Relapsing-Remitting Multiple Sclerosis in the United States” (abstract #P0857) scientists will present data on the health and economic impact of fatigue in RRMS adult patients.

This study included data from the 2017 and 2019 U.S. National Health and Wellness Survey, a nationally representative self-report survey of the U.S. general adult population.

Researchers analyzed the demographics, simultaneous conditions (comorbidities), and healthcare resources of 123 patients with high levels of fatigue, 375 patients with low levels of fatigue, and 145,669 adults without MS. Fatigue in RRMS patients was assessed with the Modified Fatigue Impact Scale – 5-item version.

Data showed that RRMS patients with high fatigue levels had more comorbidities than those with low fatigue levels and adults without MS. Consistently, depression, anxiety, and insomnia were up to two times more commonly reported by patients with high levels of fatigue than by participants in the other two groups.

Similar trends were observed for annualized number of outpatient visits, emergency room visits, and hospitalizations, translating into mean annual medical care costs of $19,508 for RRMS patients with high levels of fatigue, $10,406 for those with low levels of fatigue, and $8,493 for adults without MS.

Patients with high levels of fatigue also were more likely to report long-term disability and to have lower annual household income, and less likely to be employed full-time, compared with the other two groups.

Overall, the results indicated that high levels of RRMS-related fatigue are associated with higher comorbidity and economic burdens, which “can facilitate identification of patients with MS who may require additional treatment and support to manage MS-related fatigue,” the researchers wrote.

During the MSVirtual 2020 meeting, Janssen also will host an interactive virtual booth addressing relapsing MS and fatigue, and feature a two-part educational product theater session on MS underlying mechanisms and the patient perspective on MS-related fatigue.