Experts maintain that the “next frontier” in MS therapeutics is myelin repair (Neurotherapeutics; 10(1):44-54), and Acorda Therapeutics is chasing the goal with its trial examining rHIgM22, a remyelinating antibody being studied for the potential treatment of multiple sclerosis (MS). Acorda is currently conducting a Phase I clinical trial to assess the safety and tolerability of a single dose of rHIgM22 in people with MS. The study also includes several exploratory efficacy measures. Preclinical studies have found that it promoted remyelination by stimulating oligodendrocytes to repair areas of demyelination. Preclinical studies with rHIgM22 also resulted in sustained improvements in motor activity.

This is a different approach to treating MS than existing approved therapies, which target the underlying immunemediated inflammation of the central nervous system, according to Andrew R. Blight, PhD, Acorda’s chief scientific officer. Practical Neurology™ spoke with Tony Caggiano, Vice President of Research and Development, Acorda Therapeutics, to learn more about the research.

With an agent like rHIgM22, what are some of the challenges of designing a clinical trial? How might it have differed from a more traditional MS trial?

Like all early clinical trials, our current Phase I trial is focused on safety and tolerability. We administered rHIgM22 in escalating doses to seven patient cohorts, and there were no dose-limiting side effects in those study participants. Although this study was small and unlikely to show any efficacy signal, we included biomarker, imaging, and clinical assessments to begin to explore methods to assess remyelination. One of the challenges is there are no proven methods to demonstrate remyelination, and furthermore, remyelination alone, as demonstrated through MRIs or other imaging technologies, may not meet FDA standards for approval. There also needs to be clinical meaningfulness associated with a therapy. Looking for functional improvement is different from the DMT trials, which looked at reduction of relapses—but does mirror our Ampyra trials focusing on functional outcomes. Since there are no remyelination therapies approved, it’s a bit of a new trail we’re blazing. We, and others in the remyelination space, are looking at a range of potential efficacy measures.

In our trial, we have 21 participants being followed for six months post-treatment (each patient is given a single dose of rHIgM22) to evaluate several exploratory efficacy measures. While we don’t expect to see much in the way of efficacy given the small number of patients in the trial, these exploratory measures should help inform future trial design.

How do you decide on what measures to use, and, importantly, not use? Can you give an example of a measure your team might have considered measuring, but ultimately didn’t?

This is our first human trial of rHIgM22, so safety and tolerability are the focus. We were encouraged that there were no dose-limiting adverse events in the seven doses that were administered. We are looking at a variety of exploratory efficacy measures in the cohort of participants we are following for 6 months post-treatment, including standard clinical evaluations (EDSS, T25FW), visual measures, biomarkers, MRI and MRS (magnetic resonance spectroscopy). At this point, it’s too early to tell what efficacy measures might meet FDA’s requirements for clinical meaningfulness. That said, the area of remyelination is a promising one for people with MS, since there is a large amount of preclinical data on efficacy and the potential to repair damage from MS. Time will tell if that can translate to an effective therapy for humans.

The final data collection date for primary outcome measure is set for november 2014. Are you still on target, and when do you expect to release your findings?

Acorda expects the study to conclude later this year and plans to announce top-line safety data in early 2015.