Leber's Hereditary Optic Neuropathy
Leber's Hereditary Optic Neuropathy (LHON) is a rare, maternally-inherited progressive disease resulting in irreversible loss of visual acuity and blindness, and thus has a dramatic impact on patients quality of life. Although rare with an estimated prevalence in Europe of approximately 2.3 per 100,000, it is one of the most common mitochondrial (mtDNA) disorders. LHON can affect both men and women and develop at any time between childhood and old-age, but it is typically diagnosed in young, otherwise healthy men.
The usual presentation of LHON is that of progressive, painless loss of central vision in one eye, rapidly followed by a similar loss of vision in the other eye such that about 97% of LHON patients have bilateral vision loss within 1 year of the initial onset of symptoms.
About 95% of LHON patients harbor one of three pathogenic mtDNA mutations at nucleotid positions G11778A, G3460A or T14484C. Not all mutation carriers will become symptomatic, and male individuals get affected about five times more frequently than females. These mutations adversely affect the biochemical processes that ensure the cellular production of energy leading to dysfunction and eventual loss of retinal ganglion cells, which causes vision loss and blindness.
In the double-blind, randomized, placebo-controlled RHODOS study, 85 participants were treated either with 900 mg idebenone/day (3 times 300 mg) or placebo during 24-weeks. For a description of the RHODOS results, click here Klopstock et al: A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy. Brain. 2011; 134:2677-86.
RHODOS-OFU, a single-visit, observational follow-up study of patients who participated in RHODOS, provided additional data on disease progression following discontinuation of study treatment. The study was conducted to assess the persistence of any benefit in visual acuity obtained from idebenone treatment during the RHODOS study. For the study results, click here Klopstock et al: Persistence of the treatment effect of idebenone in Leber's hereditary optic neuropathy. Brain. 2013 136(Pt 2):e230.
Santhera re-submitted a marketing authorization application (MAA) in Europe for RaxoneŽ for the treatment of LHON. The MAA is based on additional clinical efficacy data and following pre-filing advice from EU member states. A decision by the European Medicines Agency is expected in the first half of 2015. RaxoneŽ would become the first product authorized for the treatment of this rare, inherited disease.
In France, the French National Agency for the Safety of Medicine and Health Products (ANSM) granted a temporary authorization for use for RaxoneŽ in LHON patients in France based on a data package comparable to the submitted MAA dossier.