Risdiplam / Evrysdi / RG7916
Pages in this website section last updated 10th August 2020
10th August 2020
Risdiplam Approved for the Treatment of SMA in the U.S.
Scroll down further for:
- What is it?
- How it Works
- Clinical Trials
- Global Pre-Approval Access Programme
- Progress Towards Licensing and Access
What is it?
Pharmaceutical company Roche has been leading the development of this small molecule that targets and encourages the SMN2 ‘back-up’ gene to produce a greater amount of functional SMN protein, which is lacking in people with SMA.
Risdiplam is being studied in a broad range of patients who have SMA from birth to 60 years of age. It is an orally-administered liquid designed to provide a sustained increase in SMN protein centrally and peripherally, through daily dosing.
How it Works
Risdiplam works by interacting with the SMN2 gene.
Risdiplam is a small molecule drug that specifically modulates how effectively the SMN2 gene is used to make SMN protein. It does this by interacting with SMN2 RNA (which serves as a template from which SMN protein is made) so that more SMN protein is made.
To make SMN protein from SMN2, the gene must first be copied into RNA (the template). The SMN2 gene is not as good at this process as the SMN1 gene, and therefore produces a lot less SMN protein than SMN1.
Risdiplam is being studied in clinical trials:
FIREFISH: SMA Type 1, 21 children aged 1-7 months
SUNFISH: SMA Types 2 and 3, 51 people aged between 2-25 years
JEWELFISH: a trial for people who have previously participated in a trial with SMN2-targeting therapies, or olesoxime, or who received previous treatment with nusinersen; people aged 6 months-60 years
RAINBOWFISH: a trial of risdiplam in infants with genetically diagnosed SMA who are not yet presenting symptoms (pre-symptomatic); 25 children
Trials have recruited from around the world, including for JEWELFISH in the UK. For the latest updates on trial recruitment, please go here.
Risdiplam has been shown to improve motor function for SMA Type 1 (FIREFISH), as well as Types 2 and 3 (SUNFISH), without any major, treatment-related safety issues, and is currently under consideration for regulatory approval in the USA.
People in the SMA Community have also been asking about the impact risdiplam may have on fertility and menstruation.
Global Pre-Approval Access Programme
Roche has initiated a global Pre-Approval Access (PAA) / Compassionate Use Programme (CUP) for risdiplam. A CUP enables patients who are facing the most urgent medical need and have no other treatment options, to access investigational therapies before these receive regulatory approval. Access is strictly regulated and varies between countries. It is already available for patients who have SMA Type 1 in participating countries within the European Union and will expand to patients with SMA Type 2 when Roche files for a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA). This is currently planned for mid-2020.
In the UK, access to this programme is via the Early Access to Medicines Scheme (EAMS). This is regulated by the Medicines and Healthcare products Regulatory Agency (MHRA). Roche UK submitted their application for an EAMS on 4th May 2020. An EAMS application usually takes approximately 90 days to process, although in some circumstances it can be a little less.
In the meantime, Roche UK will consider individual compassionate use applications made by healthcare professionals on behalf of their patients who have SMA Type 1 and meet the programme’s criteria.
Progress Towards Licensing and Access
Roche is seeking a broad label for the treatment of SMA in paediatric and adult patients – that’s access for those who have SMA Type 1, Type 2 and Type 3.
In November 2019, the Food and Drug Administration (FDA) granted risdiplam priority review as a New Drug Application (NDA). On 7th August 2020, the FDA approved risdiplam for the treatment of 5q SMA in adults and children 2 months of age and older. In the U.S., Risdiplam's brand name is Evrysdi™.
Roche anticipate filing a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) by mid-2020.
Procedures for access to approved medicines are managed by the National Institute for Health and Care Excellence (NICE) and the Scottish Medicines Consortium (SMC). Currently, they may not recommend access wider than an EMA licence and may limit access based on their assessment of the evidence for the clinical and cost effectiveness of a treatment. Roche is working with both authorities.
On 24th February 2020 we submitted our comments in response to NICE’s pre-referral ‘draft scoping’ response request. This gathers evidence so that NICE can decide if this is a suitable treatment for them to appraise and potentially recommend for NHS funding. You can read what we have said, here. On 7th April 2020, NICE announced its decision to suspend the scoping due to COVID-19. On 6th May 2020 we wrote to NICE urging them to continue with the appraisal.