EMA rejects Santhera’s Raxone
21.01.2013 - The EMA has withdrawn an MAA of Switzerland’s Santhera for Raxone, a synthetic coenzyme Q10 derivative against hereditary blindness.
The EU regulatory authority argued that Santhera had investigated too few patients with Leber's Hereditary Optic Neuropathy during clinical development. However, as in the case of uniQure’s currently approved orphan drug Glybera, Santhera plans to ask the EMA’s Committee for Medicinal Products for Human Use (CHMP) to reconsider its treatment based on the clinical need the drug addresses. Only a narrow majority of CHMP had voiced concerns about the reliability of the results.
"Since there were no concerns expressed about the safety of Raxone and the observed treatment benefit on visual acuity in these patients was clinically relevant and consistent with the published literature, we believe that we should be allowed to address the remaining concerns through further confirmatory clinical work to be conducted post-approval," Santhera CEO Thomas Meier said in a statement.
LHON is caused by mutations in mitochondrial DNA. The genetic disorder typically presents in young men, as loss of vision in both eyes, leading to blindness within a few months after the onset of symptoms. More than 95% of patients harbour one of three pathogenic mutations of the mitochondrial DNA, which cause a defect in complex I of the mitochondrial respiratory chain. The defect leads to decreased ATP production, increased oxidative stress and retinal ganglion dysfunction which cause progressive loss of visual acuity and blindness. Raxone (idebenone), a synthetic short-chain benzoquinone and a cofactor for the enzyme NAD(P)H:quinone oxidoreductase (NQO1) is capable of transferring electrons directly onto complex III of the mitochondrial electron transport chain, thereby circumventing the complex I defect.