Sarepta to Begin Phase 3 Rivalry with Pfizer after its DMD Gene Therapy Registers Encouraging Data

In January, when Sarepta Therapeutics reported mixed Phase 2 results of its investigational gene therapy for Duchenne muscular dystrophy (DMD), its stocks plunged by almost 50%. Results showed that although the therapy increased target protein levels, it failed to significantly improve patients’ motor skills. However, with encouraging results obtained from a latest study, the Cambridge, Mass-based company would be hoping to give a tough fight to its closest rival, Pfizer.

On May 18th, Sarepta announced positive data from its Study SRP-9001-103 (ENDEAVOR), which had enrolled 20 patients between the ages of four to seven. Data from the first 11 patients showed that the gene therapy candidate, SRP-9001 demonstrated strong transduction of the micro-dystrophin gene, resulting in robust expression (~55% of the normal) of the properly localized micro-dystrophin protein, without any new or unexpected safety signals. After the announcement, shares of Sarepta closed 8.4% higher.

SRP-9001’s Unique Mechanism of Action

Due to a mutation in the DMD gene, Duchenne muscular dystrophy patients fail to make the functional micro-dystrophin protein on their own, leading to a progressive loss of muscle strength.

SRP-9001 uses a harmless adeno-associated virus (AAV) called AAVrh74 to deliver a trimmed-down copy of the micro-dystrophin-encoding gene to patients’ muscle cells, enabling them to produce a smaller but still functional protein.

Study results showed that after 12 weeks of treatment with a single infusion of SRP-9001 at a dose of 1.33×1014 vg/kg, micro-dystrophin was properly localized to the muscle sarcolemma, with patients achieving a mean percentage of dystrophin positive fibers of 70.5%.

The totality of historical data indicates that Sarepta’s AAVrh74 vector may have intrinsic safety advantages over Pfizer’s AAV9 based approaches, which will give it an edge in clinical trials and commercial settings.

Market Competition

Besides the superior efficacy and safety profile, Sarepta’s gene therapy registered an average 6-point improvement on the North Star Ambulatory Assessment, which measures motor skills.

Although Pfizer’s DMD gene therapy data looks promising, complement-linked side-effects persist, raising safety concerns. Meanwhile, Solid Bio’s investigational candidate has been under a partial FDA hold since November after the company reported side effects in a sixth patient, including decreased red blood cell and platelet counts, acute kidney injury, and complement activation.

While Pfizer and Solid Biosciences (SLDB) are trying to undercut Sarepta, the company still has a leg up over its rivals in terms of safety and efficacy profile. If SRP-9001’s safety and efficacy profile continue to hold up, Sarepta’s competitive position will be reinforced further in the market.

Sarepta has a strong commercial DMD portfolio with three marketed drugs — Exondys 51, Vyondys 53, and Amondys 45 — developed using its exon-skipping technology. Moreover, the company is also developing a next-generation exon-skipping DMD candidate, SRP-5051, which has demonstrated tremendous potential as a treatment for DMD. SRP-9001 has exhibited block-buster potential, with the data setting the stage for improving investor sentiments. If it manages to pass regulatory checkpoints, it will further boost Sarepta’s DMD dominance in the market.

By Isha Kapoor, Ph.D.

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Isha Kapoor