Risdiplam / RG7916 

Page last updated 16th January 2020

  • What is it?
  • How it works?
  • Clinical Trials
  • Global Access Programme
  • Progress towards licensing and access in the USA, Europe and the UK

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.

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Clinical Trials

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: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: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.

To date, there have been no drug-related safety findings leading to withdrawal from any study. Roche presented data from the trials at the October 2019 Annual Congress of the World Muscle Society, demonstrating risdiplam has been well tolerated at all dose levels and in all clinical studies for all Types of SMA. In November, it presented further data from its SUNFISH trials.

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Global Access Programme

Roche has initiated a global Pre approval Access (PAA) / Compassionate Use (CU) programme for risdiplam. A PAA / CU programme 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 to these programmes is strictly regulated and varies from country to country. It is already available for patients in participating countries within the European Union with SMA Type 1 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 aims to apply for an EAMS for risdiplam in the first half of 2020. 

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.

Read more about the programme

Progress towards licensing and access in the USA and Europe

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 the USA in November 2019, the Food and Drug Administration (FDA) granted risdiplam priority review as a New Drug Application (NDA). A Priority Review status is given for drugs that, if approved, would represent significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications. The FDA is expected to review this application within 6 months with a decision to be announced on 24th May 2020. This is instead of the standard 10-month review period. If approved, risdiplam would be the first at-home administered medicine for people living with SMA.

This NDA filing includes results from a broad SMA patient population, including SMA Type 1, Type 2 and Type 3 patients demonstrating improvements in motor functions and developmental milestones and a compelling safety profile.

In Europe, Roche anticipate filing a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) by the middle of 2020.

In the UK, licensing procedures for medicines are managed by the National Institute for Health and Care Excellence (NICE) and the Scottish Medicines Consortium (SMC). Currently, these regulatory authorities may not recommend access wider than an EMA licence and they 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. We have no further information on timelines at the moment. We have, however, on 24th Feb 2020 submitted our comments in response to NICE’s pre-referral ‘draft remit and draft scoping’ response request. This process gathers evidence so that NICE can decide if this is a suitable treatment for them to appraise to see if they would recommend it is funded by the NHS. If they do consider it suitable, this also helps with any decision about what timeline they will set for this. You can read what we have said, here.

Read More about Access Routes in the UK

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