BioWorld International Correspondent
Italian CNS drug development company Newron Pharmaceuticals SpA aims to move its lead compound, safinamide, into Phase IIb clinical trials this spring in order to extend promising preliminary results it obtained in a Phase II trial of the molecule in 151 patients with Parkinson's disease.
In a double-blind parallel study, conducted in Italy, France, Germany, Belgium and Poland, subjects were randomized to receive daily doses of either 0.5 mg/kg of body weight, 1.0 mg/kg or placebo over a three-month period. Participants were either treatment naive or were in receipt of dopamine agonist therapy. The primary efficacy endpoint was a 30 percent reduction in the Unified Parkinson's Disease Rating Scale III motor score, a standard measure of disease severity.
Patients in the higher dose group who also were taking dopamine agonist medication exhibited a statistically significant improvement in function, as compared with those receiving placebo. Patients who received safinamide only also displayed motor improvement, but that was not statistically significant, "most likely," the Bresso-based company said, "because of a strong placebo response that is known to be still present after three months."
"We're planning to repeat the study over a six-month duration, which should, of course, get rid of the placebo effect," Newron Chief Scientific Officer Ruggero Fariello told BioWorld International. The precise shape of the upcoming study will depend on the outcome of talks with the FDA and the European Medicines Evaluation Agency in London. "For the time being, we plan to have one in Europe, one in the U.S.," Fariello said. The company is hoping for a fast turnaround.
Safinamide, which also is in Phase II clinical trials for epilepsy, acts via several mechanisms and, according to Newron, has both neuroprotective and therapeutic potential. It reduces the development of excitotoxicity in dopamine neurons caused by high frequency discharge. It is both a calcium and sodium channel blocker, and thereby can reduce the level of toxic events associated with excessive calcium influx in the neurons of Parkinson's patients. It contributes to a reduction or abolition of glutamate release, Fariello said, while the compound also is a selective and reversible inhibitor of monoamine oxidase B, which is involved in levodopa catabolism.
The fact that safinamide appears to act synergistically with dopamine agonists suggests that it could be administered in combination with such drugs, which could pave the way for clinical acceptance. "That route is certainly the easier one, but perhaps it's not the best one from the scientific perspective," Fariello said. The company aims to demonstrate efficacy of safinamide administered on a solo basis.
Newron was formed in 1998 through a management buyout from the CNS research center of Pharmacia & Upjohn, now Pharmacia Corp., of Peapack, N.J. The latter organization retains a single-digit royalty position in the compound, but does not hold any Newron stock.
Safinamide is not yet partnered, but discussions with several prospects are under way, said Marco Caremi, Newron's vice president of business development. Its progress in the more lucrative epilepsy indication will influence the outcome of talks. "We would prefer to license the product as it is for both indications to a single company," he said. In Europe, in particular, that would make product registration easier, he said.