West Coast Editor

MediciNova is talking with advisors to figure out the next steps toward Phase III trials after its MN-166 garnered mostly positive results in a Phase II study that tested 297 patients with relapsing multiple sclerosis.

Meanwhile, an independent data safety monitoring board recommended that the trial continue beyond the first year of treatment with no changes.

Wall Street wasn't jumping up and down about the results. Shares of MediciNova (NASDAQ:MNOV) closed Tuesday at $10.82, a rise of 4 cents - possibly because MN-166 failed to reduce the cumulative number of lesions on cranial MRI scans over 12 months compared to placebo, which was the primary endpoint of the study. Positive indicators did show up in radiological outcome measures, though, including the volume of gadolinium-enhancing (T1) lesions (p=0.09) in patients on drug compared with placebo.

MN-166 works by inhibiting leukotriene activity, phosphodiesterases and nitric oxide synthase - each an inflammatory mechanism known to be involved in MS. San Diego-based MediciNova got the drug from Kyorin Pharmaceutical Co. Ltd., of Tokyo, which holds licenses worldwide, except Japan, China, Taiwan and South Korea. It's branded Ketas (ibudilast) in Japan and Korea, and is used to treat asthma and vascular disorders in the brain.

MN-166 "sounds like a antioxidant or neuroprotectant, and those traditionally have fared very poorly in the central nervous system arena," said Andrea Witt, analyst with Decision Resources in Waltham, Mass. "They've pretty much fallen off the radar screen," she added, citing as the most recent fiasco NXY-059, also known as Cerovive, from London-based AstraZeneca plc and partner Renovis Inc., of South San Francisco, which failed in a 2,300-patient Phase III stroke trial. (See BioWorld Today, Oct. 27, 2006.)

Witt, though, called the data from MediciNova's trial with MN-166 "encouraging." Many drugs go after the immunological aspects of MS, she noted, but "you're really not preventing neurons from dying. A drug that could work as an anti-inflammatory and protect neurons would be very interesting."

Results with MN-166 showed a significant increase in the proportion of patients who remained relapse-free over the first 12 months of treatment with 60 mg per day of MN-166 compared to placebo (p=0.03), and the time to first relapse also was significantly increased (p=0.04).

Scientists found positive trends in the annualized relapse rate, too (p=0.08), and number of relapses (p=0.10) among patients who completed the full first 12 months of treatment, compared to those on placebo for 12 months. The compound also brought about a significant reduction in brain volume loss (p=0.04), as measured by cranial magnetic resonance imaging scans.

Dosing 30 mg rather than 60 mg per day brought about no clinical or radiological benefit, but the compound was well tolerated at all doses. Eighty-nine percent of patients completed the first 12 months of the trial with only mild gastrointestinal side effects observed with MN-166 (3 percent to 6 percent) compared to placebo (1 percent to 3 percent).

"The trends toward efficacy are nonsignificant in the radiological data," Witt said, but "overall, physicians we talk to don't value radiological data as much as the effect on disease, [delaying] the time to first relapse. I would like to see more convincing data [with MN-166] on disease progression."

Also reporting positive Phase II data this month were Biogen Idec Inc., of Cambridge, Mass., and Fremont, Calif.-based PDL BioPharma Inc., who said the ongoing CHOICE trial, met its primary endpoint in relapsing MS patients being treated with interferon beta. Patients given daclizumab 2 mg/kg subcutaneously every two weeks showed a significant reduction in the number of new or enlarged gadolinium-contrast-enhancing lesions at week 24, and the firms plan a Phase II monotherapy trial with the humanized monoclonal antibody, which targets the IL-2 receptor on activated T cells.

Daclizumab shows promise radiologically but has "not much of an effect on disease progression," Witt said, and found more promise in MN-166. But she and colleague Bethany Kiernan put even more chips on FTY720 (fingolimod), from Novartis AG, of Basel, Switzerland, and Osaka, Japan-based Mitsubishi Pharma Corp.

"Everyone would like to see an oral therapy come to market," Kiernan noted (current therapies are injectables), and FTY720 is ahead of MN-166, in Phase III trials.

FTY720 works by binding to the sphingosine 1-phosphate receptor-1 on a proportion of circulating lymphocytes and reversibly traps them in the lymph nodes. Its "efficacy is at least as good as the interferons out there," Witt said.