Santhera Pharmaceuticals AG is beginning its Phase III program in the U.S. to evaluate SNT-MC17 in Friedreich's ataxia, an indication for which approval of the product already is being sought in Europe.
The Swiss company reached agreement with the FDA on a special protocol assessment for the study, a randomized, double-blind trial that will test two doses of the small-molecule agent against placebo in at least 51 patients ages 8 to 17.
Klaus Schollmeier, CEO of Liestal-based Santhera, said on a conference call Friday that the trial is expected to begin enrollment in a few weeks, following approvals from the two sites: the Children's Hospital of Philadelphia and the School of Medicine of the University of California at Los Angeles.
Schollmeier said the trial design is very similar to that used in a 48-patient Phase II trial that was run by the U.S. National Institutes of Health. That study also was designed to run for six months and measured neurological improvement based on the International Cooperative Ataxia Rating Scale (ICARS).
The Phase II trial, which included endpoints beyond ICARS, showed improvements in the intermediate and high doses of SNT-MC17 (idebenone).
The Phase III trial is named IONIA, or "Idebenone effects on neurological ICARS assessments." The primary endpoint related to neurological improvements will be measured by ICARS, a 100-point scale based on 19 wide-ranging neurological assessments.
Following 24 weeks of treatment, Santhera will conduct a one-year open-label study, to further evaluate safety and tolerability in those patients who participated in the trial.
Schollmeier said the trial is expected to be completed in 2009, with market launch potentially later that year. SNT-MC17 has been granted both fast-track and orphan status by the FDA.
Friedreich's ataxia is a rare genetic neuromuscular disorder that results in the degeneration of nerve and muscle tissue, causing loss of muscle control, muscle wasting and thickening of heart walls. The disorder results from a genetic defect in the gene encoding for frataxin, Santhera said.
SNT-MC17 is believed to improve the balance and flow of electrons within the mitochondria, thus increasing energy production within nerve and muscle cells of patients and protecting the cells from cell death. Santhera said previous studies provided evidence that SNT-MC17 may be effective in disease-associated heart-wall thickening (cardiomyopathy), as well as having positive effects on neurological function.
In mid-August, the European Medicines Agency accepted for filing the marketing authorization application submitted by Santhera and partner Takeda Pharmaceutical Co. Ltd. That filing included safety data generated by Takeda in its earlier preclinical and clinical programs of idebenone for the treatment of Alzheimer's disease.
Takeda, of Osaka, Japan, would market the product for treating Friedreich's ataxia in Europe and Switzerland. Santhera has rights in the U.S. - and also in Canada, where it plans to file for approval soon. Santhera said it intends to market the product itself in the U.S. and Canada. It also said approvals in Europe and Canada are expected in the second half of 2008.
SNT-MC17, Santhera's lead product candidate, also is being developed for treating Duchenne muscular dystrophy (DMD) and Leber's hereditary optic neuropathy. On Aug. 2, Santhera and Takeda extended their commercialization partnership for SNT-MC17 in the EU and Switzerland, which began in July 2005, to cover the second indication of DMD. Data from Phase II trials in DMD in Europe are expected to be available later this year.
Santhera is entitled to milestone and royalty payments from Santhera in both indications.
There is no product in the U.S. approved for treating Friedreich's ataxia, which afflicts about 20,000 patients in both North America and Europe, Santhera said.