BioWorld International Correspondent
Santhera Pharmaceuticals AG licensed to Takeda the European rights to its Friedreich's Ataxia (FRDA) treatment, idebenone, in a deal which earned it an up-front payment of €5 million (US$6.2 million).
Other financial details were not disclosed, but Klaus Schollmeier, CEO of Liestal, Switzerland-based Santhera, told BioWorld International that his company also stands to gain milestone payments, royalties on sales plus manufacturing revenues from Takeda Pharmaceutical Co. Ltd., of Osaka, Japan. Santhera will continue clinical development of idebenone in-house.
The product is slated to enter registration trials shortly.
"We expect Europe to start [the trials], at the latest, early fourth quarter. It will be early next year before we will start in the U.S.," Schollmeier said. Nevertheless, he said he expects that the product will launch in each market at roughly the same time, around early to mid-2008, because of the FDA's faster approval times. Discussions with both it and the London-based European Medicines Agency are under way.
Santhera plans to market the product itself in North America. It had initially planned to retain global rights to idebenone but brought Takeda into the frame because of its longstanding history with and knowledge of the compound. The Japanese pharmaceutical firm originally discovered it, a synthetic analogue of the electron transport chain constituent coenzyme Q10, and it previously obtained regulatory approval for its use in Japan as a treatment for dementia. That was subsequently withdrawn, due to lack of efficacy.
A group at the Paris-based Unit 393 of the National Health & Medical Research Institute (INSERM) reported on the beneficial role of idebenone in treating FRDA in 1999. Santhera holds the license to their use patent for the U.S., while the product is off-patent in Europe, said Santhera Chief Scientific Officer Thomas Meier. FRDA is an autosomal recessive disease caused by a deficiency in the gene encoding the mitochondrial protein frataxin. It leads to a loss of neuromuscular coordination and progressive disability. Most patients die in early adulthood from cardiomyopathy.
The precise function of frataxin is not fully understood, but it is believed to play a role in the assembly of iron-sulfur enzymatic complexes involved in the electron transport chain. Its absence leads to iron accumulation in the mitochondrion and to oxidative damage.
"Idebenone helps either with oxidative defense and/or with the handling of electron flow along the electron transport chain," Meier said. While it has the same reactive benzoquinone group as the electron scavenger coenzyme Q10, idebenone has a shorter side chain, with a hydroxy terminal residue. It is, therefore, less hydrophobic than coenzyme Q10 and is not fully embedded in the mitochondrial membrane, although it remains associated with it. That feature, Meier said, makes it more effective as an FRDA treatment than coenzyme Q10.
FRDA primarily affects Caucasians, Schollmeier said. There are approximately 8,000 to 10,000 patients in North America and in Europe. At present, there is no drug licensed for FRDA, although some patients take either beta blockers, ACE inhibitors or anti-arrhythmias in an effort to combat their cardiovascular complications. Santhera has received orphan designation in the U.S. and in Europe. Some 150 patients have so far received idebenone, many of them in investigator-sponsored clinical trials. The primary endpoints in the forthcoming registration trials include slowing and reversal of cardiomyopathy, improvement of neuromuscular coordination and overall patient improvement, Schollmeier said.