FAQs re Access to Roche’s risdiplam Compassionate Use Programme (CUP) in the UK

24 April 2020

The following FAQs have been checked for accuracy with Roche. We hope they will help to clarify further how their COVID-19 response measures affect pre-approval access to risdiplam in the UK, including practical aspects of the programme.

Q.1. Is it possible for an infant newly diagnosed with SMA Type 1 who has not yet had any drug treatment to have access to risdiplam in the UK?

A. At this stage risdiplam is not licensed, so access to it is restricted by pre-approval, pre-marketing regulations. Nusinersen is currently the only licensed drug treatment for SMA Type 1, so is always the first drug treatment to be considered. Access to risdiplam is only possible if there are clinical reasons that mean nusinersen is not a suitable treatment. If this is the case, and the clinician thinks that the infant may benefit from risdiplam, then the clinician can apply to Roche for access to risdiplam via their global Compassionate Use Programme (CUP). There are eligibility criteria that the patient has to meet in order for a request to be granted for risdiplam compassionate use provision.

Q.2.  Is it possible for an infant newly diagnosed with SMA Type 2 who has not yet had any drug treatment to have access to risdiplam in the UK?

A. At this stage access to Roche’s global Compassionate Use Programme (CUP) is not yet possible in the UK for infants or children newly diagnosed with SMA Type 2. The CUP will open to patients who have SMA Type 2 at the point of European Medicines Agency (EMA) regulatory application, expected in mid-2020.

In April 2020, Roche changed the eligibility criteria for their risdiplam CUP to also include patients who have SMA Type 2, whose current treatment has been interrupted as a direct consequence of the COVID-19 pandemic. However, this only applies if the patient has received at least one nusinersen treatment and where efforts made to continue nusinersen treatment have proved futile due to the pandemic.

Q.3.  Can anyone who is unable to continue nusinersen treatment for any reason related to the COVID-19 situation, switch to risdiplam?

A. Nusinersen is a licensed medicine. At this stage risdiplam is not, so access is restricted by pre-approval, pre-marketing regulations. In April 2020, Roche changed the eligibility criteria for their risdiplam CUP to also include some eligible patients whose current treatment has been interrupted as a direct consequence of the COVID-19 pandemic. This only applies if the patient has a diagnosis of SMA Type 1 and cannot access treatment or SMA Type 2 and has received at least one nusinersen treatment. All possible options for delivering nusinersen treatment must have been exhausted. In the majority of cases, clinicians are able to arrange for safe delivery of nusinersen treatment. In a few cases this may not be possible due, for example, to the location of where treatment would need to be delivered in the hospital or the hospital being one that is facing particular local challenges due to COVID-19. In such cases a clinician who thinks risdiplam may benefit that particular patient may apply to Roche for access for their patient.

The CUP is not accessible for anyone who has SMA Type 3. Roche advises that this is because the CUP is a programme that was set up to address the needs of those who have been diagnosed with SMA Type 1 or 2 who, from a global perspective, are seen to have the most life-threatening unmet need.

Roche advise that the changes to eligibility in response to COVID-19 are about seeking a solution to assist those who are currently receiving treatment and are at most risk from not being able to maintain this treatment.  It is not an access to treatment route as such, so remains restricted to those who have SMA Type 1 and 2. They acknowledge the need for, and exclusion from, access to treatment for those who have SMA Type 3 in England. They also acknowledge that across the UK many young people and adults who have SMA Type 2 are still awaiting access to nusinersen. Their view is, however, that a global programme must have access rules that are appropriate and applied equally globally and is not the right mechanism to address a country’s unique regulatory approval and treatment access decisions. Updates on the progress of access to risdiplam globally and UK can be found here.

Q.4.  I would be eligible for this programme, at what point in my nusinersen treatment cycle could I start to take risdiplam instead?

A. To qualify for risdiplam compassionate use there must be a medical reason as to why you cannot continue nusinersen treatment, and / or you have had treatment interrupted directly due to the COVID-19 pandemic. Typically, patients on maintenance doses of nusinersen are treated every 120 days. You need a window of at least 120 days between your last nusinersen injection and your first dose of risdiplam. Your clinician may liaise with Roche before the 120 days to get things ready and in place. You may also be treated with risdiplam once the 120 days has lapsed.

Q.5.  How do I get on the programme and how long does it take to be approved?

A. If your clinician has agreed there is no option for the safe delivery of your nusinersen treatment, they will submit a request to Roche for a contract between them as your treating clinician and Roche as the supplier of risdiplam for you. Your clinician will advise Roche of your last nusinersen treatment date. It takes Roche some 2 – 7 working days to approve the request. Roche then have to apply to the Medicines and Healthcare products Regulatory Agency (MHRA) for approval to import the drug. This can take a total of 4-7 weeks, however can be accelerated in very urgent circumstances.

Q.6.  How often and how would I take the treatment?

A. Risdiplam is a liquid taken at the prescribed dose, at the same time each day by mouth (orally) or feeding tube, using the provided syringe.

Q.7.  How and where would my first dose of risdiplam be given?

A. When risdiplam is imported it comes as a powder that has to be reconstituted with purified water by a pharmacy. Your clinician will have made an agreement for this, usually with the pharmacy in the hospital where you normally receive your nusinersen treatment. Though Roche does not require that you receive your first treatment of risdiplam at the hospital or in the presence of a healthcare professional, this is usual practice for anyone receiving a first treatment like this. This is so that they can monitor you for any possible adverse event. Any such events must be recorded by your clinician and reported to Roche. Most adverse events in risdiplam’s clinical trial programme were mild in nature, and no patient had to stop risdiplam treatment due to safety or tolerability concerns.

Given COVID-19 and their reasons for the decision to transfer you to risdiplam, your clinician may make a different arrangement for your first treatment, for example at a hospital more local to you, but this relies on the local hospital’s willingness and facilities to do this.  As part of their COVID-19 response, Roche is exploring the possibility of a home care delivery service for anyone who is on the CUP. Where and how you receive your first treatment is ultimately the responsibility of your clinician and something you would need to discuss with them.

Q.8. How do I get my supply?

A. Home delivery of risdiplam is not currently available. You would expect to have to arrange for someone to collect your supply from the hospital pharmacy. A parent of a child or anyone nominated by a patient may collect their medicines. As part of their COVID-19 response, Roche is exploring the possibility of homecare delivery.

Q.9. How big a supply do I get and how do I store it?

A. Once risdiplam is made up, it has a shelf life of 64 days. The amount you are given and take each day depends on your weight. You will receive 6 bottles each of 80 mls (if taking the maximum daily dose) and fewer bottles if your dose is less than the maximum dose. That’s a total volume of about half a litre. These are in boxes that you must stack in your fridge as risdiplam must be kept at a temperature between 2oC and 8oC.

Q. 10. What experience is there of patients making this switch in treatment from nusinersen to risdiplam? Are there any risks?

A. There isn’t much experience of this switch. Roche’s clinical trial Jewelfish, for people aged 6 months-60 years who have previously enrolled in Moonfish with the splicing modifier RO6885247 or previously treated with nusinersen, olesoxime or AVXS-101 completed recruitment in January 2020. Full results will be available once patients have completed 24-months of risdiplam treatment.

Most adverse events in risdiplam’s clinical trial programme were mild in nature, and no patient had to stop risdiplam treatment due to safety or tolerability concerns. 

Q.11. What monitoring, guidance and support will I receive and from whom once I start risdiplam?

A. Roche requires you to report any adverse events to your clinician, who must report these to Roche. This includes such things as having a headache. Your clinician will go over what to report with you. As your treatment is via a CUP, any other monitoring and support is ultimately the responsibility of your clinician and something you would need to discuss with them.

Q.12. What are the possible negative side effects someone must look for and report?

A. Most adverse events in risdiplam’s clinical trial programme were mild in nature, and no patient had to stop risdiplam treatment due to safety or tolerability concerns.

Common adverse events (reported at a rate greater than or equal to 10 per 100 patient years of exposure) for risdiplam are fever, respiratory tract infection / inflammation, headache, vomiting, cough, diarrhoea, period pain, constipation, nausea, teething and atelectasis (when the airways and air sacs in the lung collapse or do not expand properly).

Your clinician will go over what to report with you.

Q.13. Will the gains I have made with nusinersen continue with risdiplam?

A. At the moment this is not known. You may want to discuss your individual circumstances and the clinical trial results for risdiplam with your clinician.

Q.14. Once I’m getting risdiplam under the CUP will I continue to get a supply?

A. As long as your clinician consider you are still benefiting from the treatment they will continue to order your supplies from Roche.

Your access to risdiplam via the CUP will only change if:

  • The European Medicines Agency (EMA) decides not to give Roche a license to market risdiplam in Europe.  In this case all access to risdiplam would stop. This is not expected given the clinical trial results to date.
     
  • The UK reimbursement authorities do recommend that the NHS funds access for people in your position. In this case your supply would switch from the CUP to whatever programme the NHS sets up. If this is a Managed Access Agreement your supply would be for the duration of this agreement. Whether it then continued would be determined by a further decision being made by the reimbursement authority.
     
  • You experience an adverse event that once assessed by your clinician means that you can no longer continue on treatment.

If EMA does license risdiplam but the UK reimbursement authorities don’t recommend the NHS funds access to risdiplam for people in your position, Roche would continue to supply your treatment.

Q.15. Once there are no risks to my receiving nusinersen due to COVID-19, would I have to switch back to nusinersen treatment?

A. This is for you and your clinician to discuss and decide. Once Roche has accepted you on their programme, as long as your clinician considers you are benefiting from treatment you may still receive risdiplam if you prefer.

Q.16. Once there are no risks to my receiving nusinersen due to COVID-19, can I switch back to nusinersen treatment?

A. This is for you and your clinician to discuss and decide. You can switch back to nusinersen treatment if this is your preferred option and your clinician agrees this remains a safe option for you.