ECTRIMS 2023: Treating SPMS with OCH shows promise in small study

Five of six people with secondary progressive multiple sclerosis (SPMS) treated with an experimental oral therapy called OCH saw no disease activity over six months in a small clinical trial.

That’s compared with 0% of the SPMS patients given a placebo, according to new data presented by Tomoko Okamoto, MD, PhD, of the National Center Hospital, Japan.

The findings were shared at this year’s joint meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), held Oct. 11-13 in Milan, Italy and virtually. The talk was titled, “Phase Ⅱ Clinical Trial of NKT Cell-Targeting Glycolipid OCH-NCNP1 for Patients with Relapsing Multiple Sclerosis.”

OCH (also called OCH-NCNP1) is a molecule that’s thought to activate anti-inflammatory responses, particularly from natural killer T-cells, immune cells that can produce large amounts of both pro- and anti-inflammatory molecules that influence the function of other immune cells. By activating these cells and promoting their anti-inflammatory function rather than a pro-inflammatory one, the therapy would reduce MS-driving inflammation.

“[OCH] is an oral drug with a unique mechanism that acts on immunoregulatory” processes, Okamoto said.

Data from a first-in-human study published earlier this year suggested OCH was generally well tolerated and activated anti-inflammatory immune cells as expected.

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Treating RRMS, SPMS with OCH therapy

The National Center of Neurology and Psychiatry in Japan sponsored a Phase 2 clinical trial (NCT04211740) to further explore the safety and effectiveness of OCH in people with MS.

The study enrolled 30 patients, 12 with SPMS and 18 with relapsing-remitting MS (RRMS). Two-thirds of them were female and most had been living with MS for more than a decade.

RRMS is the most common form of MS and is marked by relapses where symptoms suddenly worsen and periods of remission where they ease or disappear entirely. SPMS is a disease phase that can develop after RRMS and is characterized by symptoms worsening gradually over time, regardless of relapse activity. Historically, progressive types of MS like SPMS have proven harder to treat than RRMS.

All the participants had at least one relapse in the year before entering the study or two relapses in the two years before. None were actively having a relapse when the study started.

They were given granules of either 3 mg OCH or a placebo, taken once weekly for 24 weeks. The study’s main goal was to test whether the treatment reduced the number of new or enlarging MS lesions visible on MRI scans of the brain and spinal cord.

Twenty-five patients completed the study. The rates of discontinuation were similar for those given OCH or a placebo.

Fewer OCH-treated patients developed new or enlarged lesions than patients given a placebo (6.7% vs. 20%). These results weren’t statistically significant, however, meaning it’s mathematically plausible the difference could be due to random chance rather than any effect of the treatment. Smaller studies tend to have less statistical power to detect significant effects, which is why clinical trials designed to test effectiveness conclusively are usually very large with hundreds of patients.

The patients given OCH also tended to have fewer relapses. Among 15 patients given OCH, nine were relapse-free over the trial, compared with just five of the 15 given a placebo. Again, these differences weren’t statistically significant.

In the overall study population, the patients given OCH also had a nonsignificant trend toward higher rates of no evidence of disease activity (NEDA), meaning no relapses, no new MRI activity, and no new disability. Two-thirds of those given OCH had NEDA, compared with one-third given a placebo.

NEDA among SPMS patients given OCH

The researchers then examined the rates of NEDA specifically in RRMS and SPMS patients. Among the patients with RRMS, five given OCH and an equal number given a placebo had NEDA, showing no differences between them.

However, among the 12 patients with SPMS, five out of six given OCH achieved NEDA over six months. None of the six SPMS patients given a placebo had NEDA, a statistically significant difference.

“In RRMS, there are no difference in the number of cases that achieved NEDA between the OCH and placebo groups. In contrast, in the SPMS group, the … NEDA achievement rate was higher in the OCH group than in the placebo group,” Okamoto said.

Similarly, all the SPMS patients were relapse-free at the end of six months. Only one out of six patients on a placebo retained that status.

Biomarker data indicated that patients treated with OCH had fewer immune cells making a pro-inflammatory signaling molecule called GM-CSF (granulocyte-macrophage colony-stimulating factor). The decrease in GM-CSF was significant for patients with SPMS treated with OCH, but not for RRMS patients given it.

“So, there was a correspondence between clinical efficacy and biomarker change,” Okamoto said.

The data suggest “OCH is a promising treatment for multiple sclerosis, especially for SPMS,” the scientists wrote in their abstract.

Note: The Multiple Sclerosis News Today team is providing in-depth coverage of the 9th joint ECTRIMS-ACTRIMS meeting Oct. 11-13. Go here to see the latest stories from the conference.