A Phase 3 trial is planned to confirm the safety and efficacy of oral ibudilast (MN-166) in treating people with secondary progressive multiple sclerosis (SPMS) without relapses, or those whose disease is not active, MediciNova announced.

Data from this single Phase 3 study may be used to request marketing approval for ibudilast with the U.S. Food and Drug Administration (FDA), the company said in a press release.

Ibudilast, a first-in-class small molecule, works to suppress three cytokines (small signaling proteins) that promote inflammation: IL-1ß, TNF-a, and IL-6. It may also increase the activity of the anti-inflammatory cytokine IL-10, and help block the signals of toll-like receptor 4 (TLR4) that is involved in inflammation. All these activities are thought to contribute to ibudilast’s ability to ease neuroinflammation.

The therapy’s anti-neuroinflammatory and its neuroprotective actions were shown in preclinical and clinical studies, warranting studies of it in progressive MS, amyotrophic lateral sclerosis (ALS) and other neurological diseases, as well as substance abuse and addiction.

“We are excited to announce our Phase 3 plan for MN-166 for progressive MS. Although two drugs have recently received FDA approval for relapsing secondary progressive MS [Novartis‘ Mayzent and EMD Serono‘s Mavenclad, both in March 2019], there remains a very large unmet medical need for secondary progressive MS patients without relapses, as the vast majority of secondary progressive MS patients do not have relapses and there is still no drug approved for long-term treatment of these patients,” Yuichi Iwaki, MD, PhD, MediciNova’s president and CEO, said the release.

Based on results from the Phase 2b SPRINT-MS study (NCT01982942), the FDA agreed the target population for the new study should be people with non-relapsing SPMS, meaning the disease is considered inactive.

A subgroup analysis of SPRINT-MS found the risk of disability progression — as measured by the Expanded Disability Status Scale (EDSS) — was 46% lower among ibudilast-treated SPMS patients with inactive disease compared to placebo. This benefit was not seen among SPMS patients with relapses.

Unlike primary progressive MS (PPMS) and relapsing/active SPMS, no medicines are approved for long-term treatment of SPMS without relapses. MediciNova believes the medical need is “highest” in people with this type of MS, and states that data from recent clinical trials indicate more than 80% of SPMS patients have non-active disease, possibly making them the largest subgroup of progressive MS patients.

The primary efficacy measure (endpoint) of the Phase 3 study will be the time to three-month confirmed disability progression, as measured by EDSS, MediciNova said, adding that endpoint had FDA support.

“With a convenient oral administration, a very favorable safety and tolerability profile, and the potential for better efficacy than other drugs for progressive MS, we believe ibudilast could become the best-in-disease drug,” Iwaki said.

Ibudilast has been approved in Japan and Korea to treat post-stroke complications and bronchial asthma for more than two decades. MediciNova licensed the therapy from Kyorin Pharmaceutical for its potential in treating relapsing-remitting MS (RRMS), and later obtained rights to investigate it in progressive MS and other neurological disorders.

The FDA placed ibudilast on its Fast Track to help speed its development as a potential MS treatment in 2016.