Medicinova Gets Green Light for MS Trial

Jul 22 2013

Medicinova Inc. received funding and regulatory approval for a Phase IIb trial of its multiple sclerosis (MS) candidate, ibudilast. 

The project is funded by a $11.3 million grant from the National Institutes of Health for a cooperative effort by the NeuroNEXT clinical trial network within the National Institute of Neurologic Disorders and Stroke.  The Cleveland Clinic will be the primary investigator for the trial, which will be carried out at 28 sites in the U.S. and will evaluate safety, tolerability and MS.  Geoffrey O’Brien, senior director of business development and strategic planning, told BioWorld Today that the amount of the grant does not reflect the real costs of running the trial, because of cost efficiencies from working with NeuroNEXT.

“If we had to hire a CRO, it would cost much more than what the dollar amount of the grant is,” O’Brien said.  There are currently no disease-modifying treatments approved for progressive MS. Ibudilast has been approved
in Japan and Korea since 1989 for cerebral vascular disorders including post-stroke dizziness, according to Medicinova.  Ibudilast is a glial attenuator that suppresses pro-inflammatory cytokines IL-1ß, TNF-a and IL-6, and
upregulates the anti-inflammatory cytokine IL-10. It is also a functional antagonist of toll-like receptor 4 TLR4).  Steroid treatment commonly used in the treatment of relapsing-remitting MS shortens the duration of attacks,
but does not change the course of the disease.  The use of corticosteroids is typically limited to a period of one to three weeks. The use of steroids for a longer term is considered too risky for MS treatment.

Immunosuppressive drugs have also been used with some success in MS, but they come with side effects that make them impractical for widespread use. That leaves an unmet need for progressive MS, which affects 250,000 to 350,000 people in the U.S. Most patients with relapsing-remitting MS will advance to progressive MS, and progressive MS patients account for about 65 percent of all MS patients.  According to Medicinova, of San Diego, the typical MS patient is diagnosed at age 30, and spends 10 to 15 years in relapsing remitting MS before moving on to secondary progressive MS.  “The patient may spend another 30 years in the secondary progressive phase. From that standpoint, the typical MS patient will spend more years in the secondary progressive phase than they will in the relapsing-remitting phase,” O’Brien said.

Medicinova estimated the total market for MS therapies at $13.9 billion worldwide, and that is for branded drugs approved for relapsing forms of MS only.  Another option, mitoxantrone (Novantrone, Amgen Inc.) has a secondary label for progressive MS.  “The problem with that is the cumulative dose is limited due to potential for cardiac toxicity,” O’Brien said.  “You cannot use mitoxantrone in the long term.”
Otherwise, according to O’Brien, the market for progressive MS therapies is “wide open.”  “We believe it’s at least as big as the market for relapsing MS,” O’Brien said. 

Medicinova has two additional NIH-funded trials ongoing for idubilast. The National Institutes on Drug Abuse (NIDA) funded a trial of idubilast for treatment of methamphetamine addiction.  That placebo-controlled, Phase II study will focus on safety and effi cacy of MN-166 for methamphetamine dependence in treatment-seeking volunteers. Half of trial participants will have a co-diagnosis of HIV, as this is a growing problem in patients with methamphetamine addiction.  Another Phase Ib/IIa trial funded by NIDA will evaluate MN-166 for opioid withdrawal, investigating idubilast as a non-opioid alternative to treatments like methadone.  NeuroNEXT is a newly created consortium carrying out studies for neurological disease through partnerships between industry and academic institutions.

Massachusetts General Hospital will be the clinical coordinating center for the trial, and Cleveland Clinic will collaborate with investigators at 28 centers in the NeuroNEXT network.  The trial will run approximately three years through completion of data analysis.

by Catherine Shaffer, Staff Writer
BioWorld TODAY, July 22nd, 2013