BioWorld International Correspondent

Santhera Pharmaceuticals AG added another clinical stage compound to its pipeline by in-licensing from Novartis AG omigapil (SNT-317), a compound that failed to show efficacy in Parkinson's disease and amyotrophic lateral sclerosis (ALS), but which may have potential in the predominant forms of congenital muscular dystrophy (CMD).

Financial terms were not disclosed, but Liestal, Switzerland-based Santhera is paying Basel, Switzerland-based Novartis an up-front fee, and would pay milestones on the entry of omigapil into a pivotal trial in CMD and on its approval in the European Union and the U.S., as well as royalties on product sales.

Novartis has retained a buy-back option on the program, which, if exercised, would result in reimbursement payments to Santhera representing a multiple of its development costs, a milestone payment on regulatory approval and royalties on product sales. Novartis also would commit to using Santhera's U.S. sales and marketing organization, which it is building in anticipation of the launch of its lead drug candidate, idebenone, in Friedreich's Ataxia (FRDA) and other indications.

Santhera will gain access to all preclinical and clinical data generated on omigapil and also will receive an option to develop the compound in other neuromuscular conditions. It also is receiving all remaining stocks of the drug substance from Novartis.

Santhera's chief science officer, Thomas Meier, spotted the potential of omigapil in treating CMD from reading the literature. Initial in vivo experiments, which have not yet been published, further extended that promise. "In animal models, we have seen prolonged survival, we have seen prevention of muscle loss, and we have seen increases in functional parameters," he told BioWorld International.

The company accordingly filed use patents on the compound in muscular dystrophy. It is now engaged in discussions with clinical experts on both sides of the Atlantic and with regulatory authorities, prior to moving the compound into a clinical trial in CMD. It can conduct the clinical development program under an open IND originally filed by Novartis.

"There's a lot of groundwork we can take advantage of," Meier said. That includes a large safety database - previous clinical trials in Parkinson's and ALS indicate that the compound is not toxic for adults, although Santhera will have to conduct additional testing to ensure that it is safe for pediatric patients, Meier said.

Omigapil is derived from Selegeline (deprenyl) but unlike the latter, it does not yield amphetamines as a breakdown product. It acts by inhibiting an enzyme called glyceraldehyde-3-phosphate dehydrogenase (GAPDH), best known for catalyzing as a key step in glycolysis, but which also plays a role in signal transduction. Omigapil appears to block Bax-dependent apoptosis, a significant component of the pathology of the most common forms of CMD.

CMD, which affects between 1 in 20,000 and 1 in 50,000 infants, differs from Duchenne muscular dystrophy (DMD) in that it is diagnosed at birth, whereas the latter is diagnosed in early childhood. Sometimes called "floppy infant syndrome," CMD varies in severity and can cause progressive muscle loss, immobility and early death. There are no approved drug therapies for the various forms of the condition.

Santhera's successful play for omigapil echoes the strategy it followed in gaining a license to its lead drug candidate, idebenone. It originally was developed by Takeda Pharmaceutical Company Ltd., of Osaka, Japan, as a treatment for dementia in Japan but was withdrawn from the market due to lack of efficacy.

Santhera breathed new life into the compound by spotting its potential in FRDA, DMD and Leber's hereditary optic neuropathy, a genetic condition that leads to blindness. The submission of a marketing authorization application for FRDA in the European Union is imminent, while a pivotal study in DMD is "well advanced," Meier said.

A third drug candidate, fipamezole (JP-1730), is about to enter a Phase IIb clinical trial for treating dyskinesia, a severe side effect that can develop in Parkinson's disease patients on long-term dopamine therapy.

Investors failed to respond to the omigapil licensing news Monday. Santhera's share price (SWX:SANN) ended the day at CHF107, having closed Friday at CHF106.70.