Products

Date: 2017-05-09

Type of information: Product launch

Product name: Raxone®

Compound: idebenone

Therapeutic area: Rare diseases - Genetic diseases - Ophtalmological diseases

Action mechanism:

• quinone/benzoquinone analog. Idebenone is a synthetic short-chain benzoquinone analog of coenzyme Q10 and a cofactor for the enzyme NAD(P)H:quinone oxidoreductase. It is capable of transferring electrons directly onto complex III of the mitochondrial electron transport chain, thereby circumventing the complex I defect and restoring cellular energy levels. By this mechanism of bypassing complex I, which is affected in all three primary mtDNA mutations causing LHON, idebenone restores electron transport and cellular energy generation in retinal ganglion cells, promoting recovery of visual acuity. It has been optimized to facilitate the transport of electrons within mitochondria, and to contribute to maintaining correct electron balance, which is necessary for the production of cellular energy. Nerve and muscle cells, including heart muscle cells, are particularly energy-demanding and are, therefore, more prone to rapid cell damage or death due to mitochondrial dysfunction. Through preserving mitochondrial function and protecting cells from oxidative stress, it is believed that Raxone®/Catena® can prevent cell damage and increase the production of energy within impaired nerve and muscle tissue in Friedreich's Ataxia and Duchenne patients. These properties are also thought to be valuable in Leber's patients where retinal cells are damaged leading to blindness.Catena® is marketed in Canada to treat Friedreich's Ataxia since 2008. Santhera decided to voluntarily withdraw the product from the market effective April 30, 2013.
• Raxone® is a hybrid of Mnesis® (45mg tablets), a medicine containing the same active substance that has been authorised in Italy since 1993 but for a different indication (treatment of cognitive and behavioural deficits due to cerebral pathologies of vascular or degenerative origin).

Company: Santhera Pharmaceuticals (Switzerland)

Disease: visual impairment in patients with Leber’s Hereditary Optic Neuropathy (LHON)

Latest news:

• • On May 9, 2017,  Santhera Pharmaceuticals announced approval by the Scottish Medicines Consortium (SMC) for restricted use of Raxone® (idebenone) in patients with Leber’s Hereditary Optic Neuropathy (LHON), with effect May 8, 2017. The Scottish Medicines Consortium accepted Raxone® (idebenone) for restricted use by NHS Scotland in the treatment of visual impairment in adolescent and adult patients with LHON who are not yet blind (i.e., they do not meet the UK criteria to be registered as severely sight impaired). Raxone® was accepted following consideration through SMC's Patient and Clinician Engagement (PACE) process, for medicines used at the end of life and for very rare conditions. Scotland is the first country in the UK to make Raxone® available for the treatment of LHON. The SMC advice takes into account the benefits of a Patient Access Scheme (PAS), which improves the cost-effectiveness of Raxone.
• • On October 1, 2015, Santhera Pharmaceuticals announced that it is launching Raxone® for the treatment of Leber's Hereditary Optic Neuropathy (LHON) in Germany, its first and largest EU market.
• • On September 9, 2015, Santhera Pharmaceuticals announced the European Commission (EC) has granted marketing authorization for Raxone® as the first approved medicine available in all 28 member states of the European Union (EU), Norway, Iceland and Liechtenstein for the treatment of visual impairment in adolescent and adult patients with Leber's Hereditary Optic Neuropathy (LHON). Raxone® is an oral medication authorized at a daily dose of 900 mg (given as 2 tablets three times a day with food), for the treatment of visual impairment in adolescent and adult patients with LHON. Treatment should be initiated and supervised by a physician with experience in LHON. Efficacy data come from Santhera's randomized, placebo-controlled RHODOS trial and from the open label Expanded Access Program, which together have demonstrated that vision loss can be mitigated or reversed in patients treated with Raxone®.
• • On 25 June 2015, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation under exceptional circumstances for Raxone®, intended for the treatment of visual impairment in patients with Leber’s Hereditary Optic Neuropathy. Raxone® will be available as 150 mg film-coated tablets. Raxone is an anti-oxidant thought to help restore mitochondrial function and prevent oxidative damage in retinal ganglion cells in LHON patients. As a result, the medicine prevents and/or reverses loss of vision in these patients. The benefits with Raxone® are its ability to improve vision in LHON patients. The most common side effects are nasopharyngitis, cough, diarrhoea and back pain. It is proposed that treatment with Raxone® be initiated and supervised by a physician with experience in LHON. • On June 5, 2014, Santhera Pharmaceuticals announced that the European Medicines Agency (EMA) has validated its Marketing Authorization Application (MAA) for Leber's Hereditary Optic Neuropathy. Validation confirms that the submission is complete and signifies that the CHMP review process has begun. Santhera expects a decision from the EMA in the first half of 2015. The validation was based upon the pivotal RHODOS trial, which showed a significantly higher proportion of Raxone®-treated patients presented with clinically relevant recovery in visual acuity (VA) compared to placebo, and on two additional datasets from the Expanded Access Program and a Case Record Survey which provide supportive efficacy and natural history data. Efficacy data from 48 consecutive patients enrolled in Santhera's expanded access program with Raxone® in the treatment of LHON show that 50% of patients achieved clinically relevant improvement in their vision and that 63% were protected from further vision loss following Raxone® treatment. The second dataset, a Case Record Survey established in collaboration with the European Vision Institute Clinical Research (EVICR) network, provides comparative data demonstrating profound vision loss and low rates of spontaneous recovery in untreated patients.
• Inclusion of the data from the EAP and CRS in the current MAA increases the number of Raxone®/idebenone-treated LHON patients for whom VA outcomes data is available to 101 (RHODOS trial alone 53) and the number of placebo untreated patients to 102 (RHODOS trial alone 28). Santhera discussed this additional evidence of clinical efficacy and the overall content of the submitted MAA dossier with several EU member states prior to proceeding with filing. Santhera reported that the validation of the MAA for LHON also represents the start of the regulatory clock for an additional indication for Raxone® in the treatment of Duchenne Muscular Dystrophy for which a clinically relevant and statistically significant benefit of Raxone® in the preservation of respiratory function was recently reported. The company currently plans to file a MAA for Duchenne Muscular Dystrophy as a variation to the LHON label and will work with the CHMP Rapporteurs to find the most expeditious regulatory approval pathway for this indication.
• • On May 7, 2014, Santhera Pharmaceuticals has announced that it has re-filed with the European Medicines Agency (EMA) a Marketing Authorization Application (MAA) for Raxone® (idebenone) in the treatment of Leber's Hereditary Optic Neuropathy. An earlier application was withdrawn in March 2013 in order to include additional clinical efficacy data. Santhera expects a decision from the EMA in the first half of 2015. Santhera discussed the additional clinical efficacy data and the overall content of the revised MAA dossier with several EU member states prior to proceeding with the re-filing. Efficacy data on Raxone® in LHON patients from an ongoing Expanded Access Program will also be presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Orlando, Florida. Santhera will now approach the US Food and Drug Administration (FDA) for discussions on a regulatory path to an US approval based on the data package filed in the European MAA.
• • On January 21, 2014, Santhera Pharmaceuticals has announced that the French National Agency for Medicines and Health Products Safety (ANSM) has granted an "Autorisation Temporaire d'Utilisation dite de cohorte" (cohort ATU), a Temporary Authorization for Use for Raxone®, in the treatment of Leber's Hereditary Optic Neuropathy. The ATU system allows patients in France to receive reimbursed treatment with a product before a marketing authorization is granted in the European Union. The temporary authorization for Raxone® was granted after an assessment by the ANSM and clinical experts of a full application dossier comprising quality, clinical efficacy and safety data, including new efficacy data collected from LHON patients participating in an ongoing Expanded Access Program. Santhera will provide Raxone®  to LHON patients in France under the cohort ATU, for which government allocation to hospitals ensures reimbursement, until a full marketing authorization is granted in the EU.
• • On March 22, 2013, Santhera Pharmaceuticals has announced its decision to withdraw, for strategic reasons, the Marketing Authorization Application (MAA) for Raxone® as a potential therapy for Leber's Hereditary Optic Neuropathy (LHON). Santhera now plans to file a new application based on emerging clinical evidence supporting the efficacy of Raxone® in the treatment of LHON. This strategy is expected to increase the probability of a successful MAA outcome and is contingent on the availability of sufficient financial resources or on the outcome of ongoing licensing and M&A discussions. As indicated in late February 2013, Santhera continues to explore strategic and financing options including product licensing for Raxone® in LHON and the possibility of a merger or acquisition. In addition, Santhera anticipates convening a Shareholders' meeting in late April/early May 2013 to present the strategic options available and to allow a decision to be reached on the future direction of the Company.
• • On January 18, 2013, Santhera Pharmaceuticals announced that it has received a negative opinion on its Marketing Authorization Application (MAA) for Raxone® as a potential therapy for Leber's Hereditary Optic Neuropathy. The CHMP has notified Santhera that a narrow majority of CHMP members deemed Raxone® not approvable at this time. Santhera believes that the clinical benefit of Raxone® in patients in whom the medical need for treatment was most urgent had not been fully considered and therefore has decided to request a re-examination of the opinion. The outcome on the re-examination can be expected to be known by mid 2013.
• • On November 16, 2012, Santhera Pharmaceuticals has announced  that the opinion of the Committee for Medicinal Products for Human Use (CHMP) on its MAA for Raxone® in the treatment of Leber's Hereditary Optic Neuropathy is expected to be obtained in early 2013.
• • On July 22, 2011, Santhera Pharmaceuticals announced that the EMA has validated the Marketing Authorization Application (MAA) for idebenone in the treatment of Leber's Hereditary Optic Neuropathy and has started to review the Company's file.

Patents:

Submission of marketing authorization application USA :

Submission of marketing authorization application UE: 2014-05-07

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE: 2013-03-22

US authorization:

UE authorization: 2015-09-08

Favourable opinion UE: 2015-06-25

Favourable opinion USA:

Orphan status USA: 2006-10-31

Orphan status UE: 2007-02-15

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes