BioWorld International Correspondent

Santhera Pharmaceuticals AG raised CHF25 million (US$19.3 million) in new funding from existing investors and moved its lead compound, SNT-MC17 (idebenone), into a Phase III trial in Freidreich's ataxia (FRDA) in Europe.

Discussions with the FDA are ongoing, but the Liestal, Switzerland-based company plans to commence a second trial in the new year in the U.S., where it already has a collaboration with the National Institutes of Health in Bethesda, Md.

NGN Capital, Oxford Bioscience Partners, Varuma AG, Merlin Biosciences Ltd., 3i Group plc, Carnegie Asset Management, GIMV, The Novartis Venture Fund, Dow Chemical Company, Clariden Biotechnology Fund, Heidelberg Innovation and the Swiss Foundation for Research on Muscle Diseases participated in the transaction.

"Everybody who could invest, invested," Santhera CEO Klaus Schollmeier told BioWorld International.

"It's an internal round, following the terms and conditions of last year's financing," said Santhera Chief Financial Officer Barbara Heller. The company, which was created last year via the merger of Swiss firm MyoContract AG and German company Graffinity Pharmaceuticals AG, raised €14 million (US$16.8 million) around the time of its formation. (See BioWorld International, Dec. 22, 2004.)

The new funding will support its Phase III program in FRDA and will support additional activities.

"It's really spread over the whole portfolio," Heller said. The cash injection will allow it to move preclinical projects into the clinic, she said, and to explore additional line extensions for idebenone. The compound already is undergoing a Phase IIa trial in Duchenne's muscular dystrophy. The company also will develop an internal marketing capability in the new year, in anticipation of its expected product launch in late 2008 or 2009.

Recruitment into the 12-month, randomized, placebo-controlled Phase III study in Europe has commenced. It will involve some 200 FRDA patients, recruited through about 10 treatment centers in Germany, the UK and the Netherlands. The study might be extended to other European Union member states. Three different doses of idebenone will be evaluated in the trial, which has two surrogate markers as primary endpoints - improvement of patients' left ventricular mass index, as measured by magnetic resonance imaging, and improvement of neurological function, as measured by changes in the International Cooperative Ataxia Rating Scale, a composite scoring system developed by the World Federation of Neurology, which assesses posture and gait disturbances, kinetic functioning, speech disorder and oculomotor disorders.

"Survival is not an endpoint," Schollmeier said. Such a study is not feasible, he said, both because of the small size of the FRDA patient population and the time and resources it would require.

FRDA is an autosomal recessive disease caused by a mutation in the gene encoding a mitochondrial protein called frataxin, which is thought to play a role in reducing oxidative damage. The condition, which usually becomes apparent during childhood or early adolescence, leads to progressive decline in motor functions and speech impairment, disability and premature death through cardiomyopathy. Santhera, which has orphan drug designation for idebenone in Europe and the U.S., has not conducted Phase II trials itself but drew on academic trials to design the study.

"The regulatory authorities have recognized those trials as being sufficient for the design of a pivotal Phase III trial," Schollmeier said.

All except one of the Phase II trials exhibited efficacy with respect to cardiomyopathy, he said. The study that failed to do so was of three months duration, and it now is known that the product takes a minimum of six months to demonstrate an effect. Less is known about idebenone's impact on the neurological symptoms of FRDA.

"Nobody has ever done that in any detail, with patient numbers large enough to see a difference [from placebo]," said Santhera Chief Scientific Officer Thomas Meier.

Because of widespread clinical experience of the compound, Schollmeier said he is confident that it will not fail the Phase III trial on safety grounds. About 200 FRDA patients already have received the drug. But millions more received it in Japan between the late 1980s and the early 1990s, where it was authorized as a treatment for dementia, although it was withdrawn due to lack of efficacy.

Takeda Pharmaceutical Co. Ltd., of Osaka, Japan, which developed idebenone for dementia, recently licensed European rights in FRDA, while Santhera has retained North American rights. (See BioWorld International, Aug. 10, 2005.)