Access to treatments

Update on Sarepta and Roche's SRP-9001 gene therapy

The Food and Drug Administration (FDA) in the United States (US) has announced that it has granted accelerated approval for the Duchenne muscular dystrophy (DMD) gene therapy treatment SRP-9001 (delandistrogene moxeparvovec).

Read the FDA’s announcement here.

This approval by the FDA means that patients in the US will be able to access SRP-9001, making it the first DMD gene therapy approved anywhere in the world, and only the 13th gene therapy approved by the FDA.

The announcement, while very welcome and a huge milestone in eventually curing DMD, only applies in the US. Britain’s drug approval body, the Medicines and Healthcare products Regulatory Agency (MHRA), will make a decision separately based upon an application by Roche, the company with the licence for SRP-9001 in the UK. We are in communication with Roche, and will update the community as they progress with the MHRA.

Roche has issued a letter to the DMD community in the UK about the FDA decision which you can read here.

What is SRP-9001?

SRP-9001 (also known as delandistrogene moxeparvovec, or dela mox) is an adeno-associated virus (AAV) vector-based gene therapy product for ambulatory patients with a confirmed mutation in the DMD gene. It is a one-time treatment designed to treat the underlying cause of DMD. A company called Sarepta has developed the therapy, and has a licensing agreement with the drug company Roche to launch SRP-9001 outside the US in places like the UK. You can read more about the history of SRP-9001 and the relationship between Sarepta and Roche in our update from December 2022 here.

Didn’t the FDA already approve SRP-9001 this year, and wasn’t this announcement scheduled for May?

On 12 May 2023, the FDA’s advisory committee voted by a narrow margin of 8-6 to recommend the treatment for accelerated approval. That vote was non-binding and non-final, but was taken into account by the FDA in their decision-making announced today. You can read our article about the advisory committee vote in our mid-May update here.

The FDA had previously scheduled 29 May 2023 as the regulatory action date, but on 24 May 2023 Sarepta announced the date was pushed back to 22 June 2023. Sarepta said in their announcement that the FDA required additional time to complete the BLA review, including final label negotiations and postmarketing commitment discussions. You can read the announcement Sarepta made on 24 May 2023 for investors here, and for the US DMD community here. Roche’s update for the UK DMD community, in response, can be found here.

What is a ‘BLA’ and ‘regulatory action date’?

A ‘Biologics License Application’ (BLA) is a company’s submission to the FDA that contains specific information on a product they want to market in the US. If the information provided meets FDA requirements, the application is approved and a licence is issued to the company.

‘Regulatory action date’ is the term used by the FDA to refer to when it should conclude their review of drug approval submissions like BLAs. The original regulatory action date for the BLA for SRP-9001 was 29 May 2023, but this was pushed back to 22 June 2023.

What is accelerated approval, and do any other DMD treatments have accelerated approval in the US?

The FDA’s Accelerated Approval Program is intended for drugs that treat serious conditions and fill an unmet medical need, and means patients can get access to a treatment faster than if it was assessed through normal methods. This is achieved through agreeing on and monitoring a ‘surrogate endpoint’ to measure the efficacy of the treatment.

The surrogate endpoint, which could be assessed with a simple blood test, replaces measuring an actual clinical benefit such as keeping patients walking for longer – which could take years to prove. Companies are still required to conduct studies to confirm the anticipated clinical benefit, and if the confirmatory trial does not show that the treatment provides clinical benefit, the FDA could remove it from the US market.

For SRP-9001, the surrogate endpoint is a gene called micro-dystrophin, which codes for a shortened form of the dystrophin protein, measured 12 weeks after treatment with SRP-9001.

In the US, there are four drugs which already have accelerated access for DMD, three of which are Sarepta’s, and all of which are exon skipping treatments.

– Exondys 51 (eteplirsen) Sarepta

– Vyondys 53 (golodirsen) Sarepta

– Viltepso (viltolarsen) NS Pharma

– Amondys 45 (casimersen) Sarepta

What is EMBARK?

EMBARK is the proposed confirmatory study, and non-age-restricted access in the US for SRP-9001 will be dependent on the EMBARK trial meeting its objectives.

The EMBARK trial (Study 301, NCT05096221) is a global, phase 3, randomised, double-blind, placebo-controlled study. 120 patients are taking part in EMBARK, and the primary outcome measure is based on changes to North Star scores. It is also the first trial of SRP-9001 to have UK clinical trials sites. The first boy in the UK on the trial, Charlie Anderson, was recruited through DMD Hub Central Recruitment Project 

The results of EMBARK are currently expected in the fourth quarter of 2023, but that could change. You can read more about EMBARK on the DMD Hub here.

What does this mean for the UK?

In the short term, this decision by the FDA does not affect the availability of SRP-9001 in the UK. British regulatory authorities will make their own decision in due course based on Roche’s application.

When will SRP-9001 come to the UK?

Currently, that is very hard to predict, and will hinge on Roche’s application with the MHRA, and then after that, with decisions by the National Institute for Health and Care Excellence (NICE).

There have been no announcements on where Roche is in that process, or what route to approval SRP-9001 will take, but Duchenne UK understands that Roche and the MHRA are currently in discussions about SRP-9001.

If you have any questions about this, you can email us at [email protected].

Published on 22 June 2023

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