Information provided to Duchenne muscular dystrophy patient organisations regarding Raxone (idebenone) and the Early Access to Medicines Scheme in the UK (EAMS 46555/0001) April 26 th 2018 Raxone tablets are available in the UK through the Early Access to Medicines Scheme (EAMS). The UK Commission on Human Medicines (CHM) undertook a review of the EAMS scientific opinion for Raxone, which is manufactured by Santhera Pharmaceuticals and is also known as idebenone. On 19 th April 2018 the CHM advised the Medicines and Healthcare Products Regulatory Agency (MHRA) that the positive scientific opinion given to Raxone in June 2017 for slowing the decline of respiratory function in patients with Duchenne Muscular Dystrophy (DMD) from the age of 10 years who are currently not taking glucocorticoids (also known as steroids ) could be maintained. The MHRA has decided to maintain the positive EAMS scientific opinion as the assessment of risk/benefit on which it made its initial decision remains unchanged. The MHRA has reviewed the latest information supplied by the manufacturer and considers that Raxone has an acceptable safety profile overall; it is also satisfied that the company is able to continue to supply the medicine according to a consistent quality standard. In conclusion, considering the very high level of unmet need in this patient population, and that the benefits outweigh the risks, continued early access to Raxone for DMD patients as defined in the scope of the EAMS indication is considered to be justified. Therefore Santhera will continue to make Raxone available through the UK EAMS scheme. A formal renewal of the EAMS scientific opinion is due to be concluded by end June 2018 enabling the EAMS to be renewed for a further year until June 2019. This medicine may not be suitable for everybody and people with DMD need to discuss their own condition with a specialist doctor who knows them to assess if this treatment is appropriate.
Frequently Asked Questions (FAQs) 1. What is the Early Access to Medicines Scheme? The aim of the Early Access to Medicines Scheme (EAMS) is to provide earlier availability of promising medicines to patients in the UK where there is high unmet clinical need, before the normal European product licensing process is completed. The medicinal products included in the scheme are those that are intended to treat, diagnose or prevent seriously debilitating or life threatening conditions where there are no adequate treatment options. The scheme is regulated by the Medicines and Healthcare Regulatory Agency (MHRA) in the UK. More information about the scheme can be found on its website here: http://www.mhra.gov.uk/howweregulate/innovation/earlyaccesstomedicinesscheme EAMS/index.htm An EAMS programme is only open to include new people until a product gets a European product licence, then no new people can be added to the scheme. 2. Why did the MHRA undertake a review of the EAMS scientific opinion for Raxone? Raxone is licensed for a rare condition (Leber s Hereditary Optic Neuropathy) but is not licensed for use in Duchenne Muscular Dystrophy (DMD). Santhera had separately applied to the European Medicines Agency (EMA) for a variation to the marketing authorisation to add the DMD indication to the existing Raxone product licence for Leber s Hereditary Optic Neuropathy. This was refused in January 2018 after an EMA committee concluded that the data of the Phase III DELOS trial alone would not support a registration at this time and further definitive data were needed. The review of EAMS by the MHRA followed this decision and consultation with clinical experts on the UK Commission on Human Medicines, with input from UK patient organisations. 3. Is the EAMS positive scientific opinion for Raxone (idebenone) in DMD maintained? Yes, as recommended by the UK Commission on Human Medicines (CHM) on 19th April 2018.
4. Will the EAMS positive scientific opinion be renewed until what date? The EAMS is to be formally renewed in June 2018 for a further year until June 2019. This regulatory procedure is currently ongoing. 5. Is the EAMS indication unchanged? Yes, the EAMS indication in DMD is unchanged. Raxone is indicated under EAMS for slowing the decline of respiratory function in patients with Duchenne Muscular Dystrophy (DMD) from the age of 10 years who are currently not taking glucocorticoids 6. EAMS has a Risk Management Plan that helps to ensure that Raxone is used safely within EAMS has that changed? No, the Risk Management Plan for EAMS has not changed directly as a result of this review, but it may need realignment following a recent change to one section of the product licence for another use of Raxone. Santhera will work with the MHRA to make any necessary amendments. 7. Has the consent of patients been amended and do any patients need to be re-consented? No, the patient consent for this EAMS has not been amended and existing patients in the EAMS do not need to be asked to re-consent. 8. How long will the EAMS be open? An EAMS is reviewed and considered for renewal each year by the MHRA, and has to close to new patients once a product licence is granted. Santhera is preparing to make a new application for a product licence, a process which is expected to take around 2 years to complete, and expects to apply for annual renewals of EAMS until then. Santhera will provide Raxone free of charge to the NHS during the EAMS period, which is defined as after the award of an EAMS positive scientific opinion and up to the granting of the product licence. Once the scheme closes, Santhera will continue to supply the medicine for people who are already enrolled in the EAMS for as long as their doctor considers it to be beneficial, up to the point of a positive NHS funding policy (e.g. Health Technology Assessment (HTA) guidance, national funding policy, local funding arrangements etc.).
9. How does the EAMS work? The EAMS allows medicines to be prescribed by UK specialist doctors to treat people before it has a product licence. This is not a clinical trial; it is more like how the medicine will be used in real life once it has a licence. However, extra care will be taken as this is an unlicensed medicine in DMD. Treatment will only be provided in specialist centres that are experienced in managing DMD and there is the requirement for careful monitoring to ensure the safety of patients during the EAMS. People with DMD may discuss together with their doctor whether they are suitable for this treatment and a joint decision would be made whether they want to go ahead. They would be asked to sign a consent form once they have considered all the information. 10. Where is the EAMS available? This EAMS is available in the UK National Health Service in England, Scotland, Northern Ireland and Wales. 11. What is Raxone? Raxone is a medicine that contains a substance called idebenone in tablet form. Idebenone is a potent anti-oxidant and is believed to improve the functioning of mitochondria that are important for the generation of energy and control of metabolic processes inside cells. Raxone comes as tablets which need to be taken three times a day with food. If someone has difficulty in swallowing, tablets can if necessary be crushed into semisolid or liquid feed for administration through a tube into the stomach. Raxone is already licensed for use in a rare, genetic eye condition called LHON (Leber s Hereditary Optic Neuropathy). 12. Who can have this treatment in the Scheme? Raxone is only available with a prescription from a specialist doctor with experience in managing people with DMD. A specialist doctor can advise on whether the scheme might be suitable for an individual person. Raxone has been approved for use within the EAMS programme to slow the rate of decline of breathing ability in patients with DMD from the age of 10 years who are not taking glucocorticoids (also known as steroids ). This is because clinical trials
have only been completed with this medicine in patients of this age with DMD who were not taking steroids. Breathing ability is usually measured by lung function tests, and typically these show that function begins to decline below the lower limit of normal in people with DMD around the time they lose ambulation and require a wheelchair most of the time. Lung function decline must be confirmed by spirometry (a test done in hospital, which measures the maximum flow and volume of air that can be exhaled in one breath) before Raxone is given. Raxone can only be given to patients not taking glucocorticoids or those previously treated with glucocorticoids, such as prednisolone or deflazacort, or in patients who are not suitable for continuation or commencement of glucocorticoid treatment. Importantly, Raxone is not a replacement for steroids and people with DMD should not decide to stop steroids solely so that they can start Raxone. A specialist doctor with experience of managing people with DMD can advise on the benefits of continuing steroid therapy for an individual person. 13. Is Raxone available for patients who are taking steroids? People with DMD who are taking steroids are not eligible for this EAMS. SIDEROS is a clinical trial designed to study whether Raxone is safe and effective at delaying the loss of respiratory function in boys and men with DMD who are currently taking steroids. Some specialist centres in the UK are able to enter people into this study. Further information can be found at www.siderosdmd.com 14. What are the possible side effects? Like all medicines, Raxone can cause side effects, although not everyone gets them. The MHRA and the Company have made available a leaflet written for people with DMD that explains more about Raxone and its effects. Specialist doctors will also be able to explain this further. A risk management plan has been developed to ensure that Raxone is used as safely as possible within EAMS. 15. Are there extra tests and hospital visits required? In most circumstances no extra tests are required for participants in EAMS beyond what is routine practice. Doctors will want to keep in touch regularly with their patients to know how they are finding the new treatment. In particular they will want to know about any side effects they experience.
16. How is the introduction of a new medicine regulated in the UK? A medicine that is proposed to be marketed in the medical condition Duchenne muscular dystrophy (DMD) must be licensed for that use in the countries of the European Union by the European Medicines Agency. The Committee on Human Medicinal Products (CHMP), of which the MHRA is a member, makes a thorough review of detailed information provided by the manufacturer of the medicine and will recommend if a product should receive an authorisation in the European Union. The information submitted includes the results of clinical trials that have been completed using the medicine in people with the condition that is being studied. 17. Why did the EMA reject the marketing authorisation application for Raxone in January 2018? Raxone already has a Marketing Authorisation (also known as a product licence ) for a rare genetic eye condition called LHON (Leber s Hereditary Optic Neuropathy) which was granted in September 2015. Santhera submitted a variation application to the EMA in May 2016 to extend the use of the product for a new indication in DMD; a variation to an existing marketing authorisation requires definitive data to be in place at the time. The EMA made its decision based on the evidence provided by the manufacturer, concluding that the data of the Phase III DELOS trial alone would not support a registration at the current time. Further data are required to support the results of the DELOS trial, particularly to support the link between the observed treatment effect on respiratory function outcomes and patient benefit. Not unusually, when investigating new medicines in rare diseases, the number of patients in the DELOS clinical trial was small and, although the study outcome was positive, the EMA has some uncertainty about the effect of treatment based on such small numbers. The evidence shows, however, that Raxone is generally welltolerated in patients with DMD. 18. Why did the MHRA renew the EAMS positive opinion for Raxone if the EMA had rejected the marketing authorisation? The EMA decision was made in the context of a variation to an existing marketing authorisation which required definitive data to be in place at the time. The aim of the Early Access to Medicines Scheme (EAMS) is to provide earlier availability of promising medicines to patients in the UK where there is high unmet clinical need, before the normal European product licensing process is completed. The MHRA had already reviewed the safety and efficacy data for Raxone in DMD and given a
positive opinion in June 2017 for supply under EAMS. The MHRA, on the recommendation of the UK Commission on Human Medicines (CHM) has decided to maintain the EAMS scientific opinion which will enable the supply of Raxone under EAMS to be continued, as the risk/benefit profile on which CHM made its initial decision remains unchanged, and there is a clear high unmet medical need for patients with DMD. CHM also acknowledged the prospect of more data from the ongoing clinical study (SIDEROS) and the opportunities for ongoing patient monitoring in the real world environment. Patients receiving Raxone through EAMS are required to be under specialist clinical supervision in order to receive treatment and they will be carefully monitored by their doctors. NP-UK-DMD-RAX-0001 Date of preparation: April 2018