LONDON – Newron Pharmaceuticals Spa has resubmitted its new drug application for Xadago (safinamide) to the FDA exactly five months after receiving a refusal-to-file letter from the agency. The move comes a week after the EMA recommended the Parkinson’s disease treatment for approval, putting the company on course for EU and U.S. launches in 2015.
Xadago becomes the first new chemical entity in 10 years to get a positive opinion from the EMA in Parkinson’s disease. The once-per-day, orally available monoamine oxidase-B (MAO-B) inhibitor blocks one of the key enzymes involved in the breakdown of dopamine and has been shown to have an effect on symptoms both in combination with dopamine agonists in the early stages of the disease, and when taken with levodopa at the more advanced stages.
Newron filed for approval in both indications, but the EMA is only recommending Xadago for use in mid-to-late-stage disease, as an add-on to levodopa and other drugs in patients who are experiencing motor fluctuations.
Despite the EMA’s recommended use not being as broad as hoped for, Samir Devani, analyst at Rx Securities in London, said the decision is a “landmark achievement” for Milan, Italy-based Newron. “Approval in Europe should provide investors comfort regarding potential U.S. approval,” Devani said, adding he is “optimistic” of Xadago achieving a broader label in the U.S.
Certainly the EMA recommendation appears to overlook one of the advantages Newron has highlighted, which is that the combination of Xadago with dopamine agonists in the early stages of the disease both delays the need to change to levodopa and reduces the dose of levodopa required when the switch is made.
The EMA’s view is that the medical need for additional medication in early stage patients, together with the magnitude of the benefit seen with safinamide in this patient group, did not provide compelling grounds for approval in this indication.
The EMA’s decision is based on the results of two phase III trials in more than 1,100 patients. Fabrizio Stocchi, director of the Parkinson’s Disease and Movement Disorders Research Center in Rome, who has been involved in the development of Xadago for over a decade, said the drug is “extremely well tolerated,” significantly improving motor fluctuations, parkinsonism and quality of life.
While Xadago will complement, rather than compete with levodopa as the mainstay of Parkinson’s disease therapy, it will be pitched against Teva Pharmaceutical Industry Ltd.’s Azilect (rasagaline), which belongs to the same class of MAO-B inhibitors.
The EMA recommendation on Xadago awaits the rubber stamp of the EC and agreements on pricing and reimbursement at a national level. However, Maurizio Castorina, CEO of Newron’s commercialization partner, Zambon Spa, said the drug will be launched in the first half of 2015.
Newron will start to see revenues during the year, leading to break even in 2016, 18 years after the company was set up around former Pharmacia and Upjohn (later Pfizer) assets.
While Zambon will handle commercialization in Europe, it will sublicense rights in the U.S. Devani said in his note that he expects significant interest and is estimating a deal worth $125 million in up-front, approval and launch milestone payments, of which half will flow to Newron. (Zambon owns 11 percent of Newron’s equity.)
The file that Newron has resubmitted to the FDA seeks approval of Xadago as add-on therapy to a stable dose of a single dopamine agonist in early Parkinson’s disease patients and as add-on therapy to levodopa alone or in combination with other treatments in mid-to-late-stage disease.
Newron said the refusal-to-file letter did not relate to any problems with the clinical data, but rather to technical issues with the hyperlinks and the list of contents of the file. The FDA has agreed to the changes, said Ravi Anand, CMO of Newron. “The refusal-to-file issues have been addressed in this submission,” he said.
News of the re-submission to the FDA pushed up Newron’s share price (Zurich:NWRN) by 6.55 percent to CHF26.85 (US$27.22) on Monday. A year ago, following the filing of Xadago to the EMA, the shares stood at CHF16.70.