Sarepta’s DMD Drug Off to a Solid Start But Elevidys Problem Lingers

It appears that Sarepta Therapeutics’ upcoming treatment for Duchenne muscular dystrophy (DMD) is effectively stimulating dystrophin expression. However, considering the recent approval of the firm’s gene therapy, Elevidys, for the same disease, analysts are questioning the significance of the data for SRP-5051. 

The company presented preliminary data from the mid-stage MOMENTUM study of SRP-5051, revealing an average dystrophin expression of just over 5% and an average exon skipping of 11% at 28 weeks, prompting scrutiny from analysts.

DMD is the result of a mutation in the dystrophin gene, leading to reduced production of the dystrophin protein essential, which is necessary for muscle maintenance. SRP-5051 aims to address this by skipping exon 51, facilitating the generation of a truncated dystrophin protein.

Notably, the levels of dystrophin expression observed with SRP-5051 were over 12 times higher than those reported for Exondys 51, a therapy approved amidst controversy in 2016 for specific DMD cases. Moreover, the exon skipping achieved with SRP-5051 marked a more than 24-fold increase compared to the earlier treatment. These outcomes remained consistent across both ambulatory and non-ambulatory patients.

However, the comparison analysts were truly keen on centered around how SRP-5051 compares to Elevidys, which obtained accelerated approval the previous year for ambulatory patients aged 4-5 years with a verified DMD gene mutation. The pertinent question remains: how will these three medications coexist in the market?

During a conference call on Monday, CEO Doug Ingram informed investors that his team has extensively deliberated on this matter for a considerable period. He conceded that the therapies are in conflict with each other, potentially leading to a cannibalization of Sarepta’s existing market share.

“We truly believe there are opportunities for both of these modalities to exist and benefit patients,” Ingram stated.

Regarding efficacy, a Sarepta spokesperson clarified that Elevidys operates differently from Exondys 51 and SRP-5051, as it does not induce exon-skipping. Consequently, comparing the new therapy with the gene therapy proves challenging as they are evaluated using different metrics.

In terms of dystrophin expression, Elevidys demonstrated a 54% change from baseline in 20 patients during the commercial-focused Study 103 trial. In contrast, the earlier developmental Study 102 observed a 39% change from baseline in 29 patients for the gene therapy. Sarepta has not yet disclosed expression data from the phase 3 EMBARK trial.

According to the spokesperson, DMD gene therapies are yielding higher levels of expression compared to previous exon-skipping medications. However, SRP-5051 continues to demonstrate superior outcomes compared to any previous medication in its class. This therapy involves adding a peptide to the Exondys 51/PMO backbone, which is anticipated to enhance dystrophin expression, increase exon skipping, and necessitate less frequent dosing.

Sarepta does not disclose the sales figures of its individual therapies. However, in a preliminary report for 2023 released earlier this month, the company attributed $945 million in revenue to the RNA-based PMO solutions, which encompass Vyondys 53 and Amondys 45, among others. 

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