BioWorld International Correspondent

Santhera Pharmaceuticals AG licensed European rights to idebenone in Duchenne muscular dystrophy (DMD) to Takeda Pharmaceutical Co. Ltd., in return for an up-front payment of €2 million, another €18 million (US$24.6 million) in milestones and royalties on eventual product sales.

The deal extends an existing pact between the companies, based on European rights to the same compound in another genetically inherited neuromuscular condition, Friedreich's ataxia (FRDA).

That agreement, which dates from August 2005, was valued at €12 million in total, including an upfront payment of €5 million. Although DMD offers a larger market than FRDA, the drug is at an earlier stage of development in this indication.

"In DMD we do not yet have proof of concept in man. It's a much earlier stage project," Santhera CEO Klaus Schollmeier told BioWorld International.

The compound is undergoing a Phase II clinical trial in DMD in 21 patients. "We expect to see the data in the fourth quarter," Schollmeier said. It then hopes to move directly into a pivotal Phase III clinical trial. Liestal, Switzerland-based Santhera has retained all other rights and plans to market the compound in this indication, as well as in FRDA, in North America.

Idebenone appears to play a role in stabilizing the cell membrane in DMD, a fatal muscle-wasting condition caused by mutations in the gene encoding the protein dystrophin. This improves the flow of calcium ions across the membrane, a process that is otherwise impaired in DMD. "It's a sort of electron-flux balancer in a way," said Schollmeier.

In FRDA, it appears to play a similar role, although in this case, it improves the flow of ions across the mitochondrial membrane and offsets the energy deficits evident in the cells of patients with that condition.

Santhera is planning to file a European marketing authorization application for idebenone in FRDA this summer, and could gain approval inside 12 months. "We are shooting for the middle of next year," Schollmeier said.

Recently issued guidelines from the London-based European Medicines Agency on clinical trials in small patient populations have enabled the company to accelerate its filing plans, before the completion of a Phase III clinical trial because of statistically significant efficacy data in earlier studies.

The compound already is in use in Switzerland, where Osaka, Japan-based Takeda has obtained temporary registration, and in compassionate-use programs in France and Italy.

In the U.S., the FDA still requires data from a Phase III clinical trial, and Santhera has submitted a trial design under the agency's special protocol assessment procedure.

The trial likely will be of a shorter duration than originally envisioned because idebenone appears to have a faster onset of efficacy than previously thought.

Idebenone also is under development in a third indication, Leber's hereditary optic neuropathy.

Recruitment for a Phase IIa clinical trial is underway. Santhera is also planning to move fipamezole into a Phase IIb clinical trial for the treatment of levodopa-induced dyskinesia in Parkinson's disease this fall.

The company acquired the product from Turku, Finland-based Juvantia Pharma Oy last September and has spent the intervening period reformulating it from an oral spray to a tablet form.

Last month, it in-licensed omigapil from Basel, Switzerland-based Novartis AG for development in congenital muscular dystrophy.