Santhera Announces Phase 4 LEROS Trial with Raxone® Achieves Primary Endpoint in Patients with Leber’s Inherited Optic Neuropathy
Pratteln, switzerland, June 23, 2021 – Santhera Pharmaceuticals (SIX: SANN) announces positive results of hislong term Phase 4 LEROSstudy with Raxone® (idebenone) in treatment of Leber’s hereditary optic neuropathy (LHON).The primary endpoint, the proportion of eyes showing a clinically relevant benefit after 12 months of treatment with Raxone compared to untreated patients an external control group, was met with high statistical significance (p = 0.002). Efficacy data confirms and extend previous results which have shown that Raxone can prevent further vision loss and promote recovery of viewin LHONthe patients.
“Raxone® represents an indispensable therapy for patients with LHON and is still today the first and only drug approved for this condition,” said Dario Eklund, CEO of Santhera. “The strong evidence of efficacy will also support market access in countries where this is not yet the case, allowing patients who do not have an alternative treatment to benefit from treatment with Raxone. “
Santhera holds the EU marketing authorization for Raxone (idebenone) and the product license rights outside of North America and France for the treatment of LHON at the Chiesi group. Subject to the completion of certain business milestones for Raxone, Santhera is entitled to conditional short- and medium-term variable milestone payments from Chiesi Group up to € 49 million.
LEROS, an open-label, externally controlled phase 4 intervention study, was designed to confirm the efficacy of Raxone in patients with LHON after 12 months of treatment and to further assess the efficacy and safety over time. 24-month term of Raxone (clinical trials. Government ID: NCT02774005). The study, which was designed with the advice and approval of the European Medicines Agency (EMA), along with the collection of natural history data used as an external control, was part of a post-authorization commitment .
The positive results confirm and extend the earlier results of the double-blind, randomized, placebo-controlled RHODOS trial (, ClinicalTrials.gov Identifier: NCT00747487) and data from an extended access program (also as part of post-authorization engagement), both of which showed clinically relevant beneficial responses to Raxone in patients with LHON . Treatment benefit manifests itself in clinically relevant stabilization (CRS) or clinically relevant recovery (CRR) of visual acuity or both .
“These results confirm the effectiveness of idebenone in the treatment of LHON by dramatically increasing the chances of vision recovery and / or preventing further vision loss,” said Thomas Klopstock, MD, professor of neurology at the University of Munich, LHON researcher and principal investigator of the LEROS study. “LHON is a particularly devastating disease because people with the disease, who are otherwise healthy and often young, quickly become blind bilaterally within months. Most will remain blind permanently if they are not treated.
The primary objective of the LEROS study was to assess the effectiveness of Raxone (150 mg tablets, 900 mg daily dose) in promoting recovery or stabilization of visual acuity (VA) after 12 month. This was evaluated in patients starting treatment up to one year after the onset of symptoms, compared to an untreated, matched, natural history (NH) external control group. The study, conducted in 199 patients, met its pre-specified and agreed primary endpoint and key secondary objectives, including confirmation of its overall favorable safety profile during long-term treatment. After 12 months of treatment, 43.1% of patients treated with Raxone achieved a clinically relevant benefit (CRB) with high statistical significance compared to 20.7% in the NH group (p = 0.002; OR [95% CI]: 2.286 [1.352; 3.884]). The beneficial effect of the clinically relevant treatment was maintained at 24 months compared to the NH group (p = 0.0297; OR [95% CI]: 2.082 [1.074; 4.099]). Positive results were also observed after 12 months of treatment in patients starting treatment with Raxone> 1 year after onset of symptoms, one of the secondary endpoints, compared to the NH population (p = 0.0058; OR [95% CI]: 1.994 [1.219; 3.296]). Santhera conducted the LEROS trial at 31 study sites in nine European countries and the United States.
 Klopstock T, et al. Brain. 2011 Sep; 134 (Pt 9): 2677-86.
 Summary of product characteristics for Raxone, available here
 Catarino CB et al. Actual clinical experience with idebenone in the treatment of Leber’s hereditary optic neuropathy. J Neuroophthalmol. 2020 Dec; 40 (4): 558-565.
About Leber’s and Raxon’s Hereditary Optic Neuropathy
Leber’s hereditary optic neuropathy (LHON) is an inherited genetic disease causing deep vision loss and blindness. The disease presents in young adults, more commonly in men, as a rapid and painless loss of central vision, usually leading to permanent bilateral blindness a few months after the onset of symptoms. About 95% of patients have one of three pathogenic mitochondrial DNA mutations, which cause a defect in the complex I subunit of the mitochondrial respiratory chain. This defect results in decreased cellular energy production (ATP), increased production of reactive oxygen species (ROS), and dysfunction of retinal ganglion cells, which results in progressive loss of visual function.
Raxone® (idebenone), a synthetic short-chain benzoquinone and a cofactor of the enzyme NAD (P) H: quinone oxidoreductase (NQO1), has been shown to promote recovery of visual acuity by bypassing the I-complex defect , thereby reducing and trapping ROS, as well as restoring cellular energy levels in retinal ganglion cells. The new data confirm previous findings that approximately 50% of patients can benefit from treatment, either by preventing the progression of visual acuity loss or by experiencing clinically relevant recovery of visual acuity. In September 2015, Raxone received marketing authorization from the European Medicines Agency (EMA) for the treatment of patients with Leber’s hereditary optic neuropathy (LHON).
Santhera Pharmaceuticals (SIX: SANN) is a Swiss pharmaceutical company specializing in the development and commercialization of innovative drugs for rare neuromuscular and pulmonary diseases with high unmet medical need. Santhera holds an exclusive license for all indications worldwide for vamorolone, a first-class dissociative steroid with a novel mode of action, which was investigated in a pivotal study in patients with DMD as a alternative to standard corticosteroids. The clinical-stage pipeline also includes lonodelestat (POL6014) to treat cystic fibrosis (CF) and other neutrophilic lung diseases, as well as an exploratory gene therapy approach targeting congenital muscular dystrophies. Santhera has licensed the rights to its first approved product, Raxone® (idebenone), outside of North America and France for the treatment of Leber’s hereditary optic neuropathy (LHON) to the Chiesi Group. For more information, please visit www.santhera.com.
Raxon® is a trademark of Santhera Pharmaceuticals.
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