Sarepta Therapeutics, a leading player focused in developing precision genetic medicines for rare diseases with more than 25 programs ongoing, has recently announced the submission of New Drug Application (NDA) to the US FDA for Casimersen (SRP-4045) for the treatment of Duchenne muscular dystrophy (DMD) with a genetic mutation that is amenable to skipping exon 45 of the Duchenne gene.

The company has announced the results of Casimersen to placebo in the ESSENCE trial (NCT02500381) study, also known as study 4045-301, a global, randomized double-blind, placebo-controlled Phase 3 study testing the efficacy and safety of casimersen and golodirsen in patients amenable to skipping exons 45 and 53, respectively.

Casimersen is designed to work by Sarepta’s phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology and is administered once weekly through intravenous (IV) infusions. The technology directs the drug to bind to the exon 45 of the dystrophin pre-mRNA leading to skipping of this Exon, with the remaining ones in the right sequence, ergo, producing a short yet functional dystrophin protein, henceforth delaying muscle wasting.

In addition to this, Sarepta has several treatments in its pipeline for DMD including SRP-5051, SRP-5053, SRP-5045, SRP-9001 Micro-Dystrophin and others; however, they are in either clinical or pre-clinical stages.  Furthermore, not long ago, the company announced promising results from a small study of SRP-9003, its gene therapy for limb-girdle muscular dystrophy Type 2E (LGMD2E).

Duchenne Muscular Dystrophy is a rare genetic disorder, which is caused due to the lack of functional dystrophin protein due to the missing of exons in the dystrophin gene. DMD is characterized by muscle weakness and over the time heart and breathing muscles also begin to deteriorate, and ultimately the disease proves to be lethal. Most patients by the age of 12 start to use a wheelchair. Inherited in X-linked recessive pattern, DMD mostly affects males; however, in an unusual, rare case, it can also affect females. The total diagnosed Duchenne Muscular Dystrophy prevalent population in the 7MM was found to be 27,685 in 2017, estimated DelveInsight.

With no cure at present, the current US Duchenne Muscular Dystrophy Market is mainly dominated by the use of Glucocorticoids (Prednisone, Prednisolone along with several others) and approved therapies, which include both Exon skipping therapies (Exondys 51 and Vyondys 53) and another approved corticosteroid Emflaza (PTC Therapeutics).

Exondys 51 (eteplirsen), which even though in a very dramatic manner managed to get approval in 2016. The therapy is for the DMD patients with a confirmed mutation amenable to exon 51 skipping. Although, the accelerated approval faced a lot of criticism because of lack of evidence of clinical benefit in disease progression, the FDA’s approval to Sarepta’s Vyondys 53 (golodirsen), last year, left the healthcare industry baffled. The approval of the therapy demonstrated that the adequacy of dystrophy as a surrogate for winning FDA’s accelerated approval in case of DMD, a rare disorder with high unmet needs.  It is not to be missed that the Vyondys 53, just like Exondys 51, has won conditional approval and the final approval is based on the ESSENCE trial (NCT02500381) which is in Phase III and a post-marketing trial. However, the launch of Viltolarsen by NS Pharma, which is an Exon-53 skipping therapy is bound to give a significant face off to Sarepta’s Vyondys 53.

Besides Sarepta, other pharma companies that are investing in the Duchenne Muscular Dystrophy Market are Nippon Shinyaku, Italfarmaco, FibroGen, Daichi Sankyo, Taiho Pharma, Catabasis Pharmaceuticals, Pfizer, Santhera Pharmaceuticals, Taiho Pharmaceuticals and others. Italfarmaco’s Givinostat, Catabasis’s Edasalonexent are some of the other pipeline therapies in the DMD market.

Even though the therapies exist in the DMD market, the controversies regarding their use exist too.The therapies are not curative. Moreover, the therapies target only a fraction of the patients such as Vyondys 53 only targets 13% of the DMD patient pool with no proven clinical efficiency. Other therapies that have the potential to target the whole of the DMD patient pool, such as Ivinostat (Italfarmaco) have not yet been blessed by the regulatory agencies. The rarity of the disease, as well as the heterogeneity of the patients, makes it more challenging to conduct a clinical trial. Not to forget, the cost factor and RoA methods that can be quite challenging while administering to children.

However, the launch of emerging therapies in the Duchenne Muscular Dystrophy Pipeline, mostly which are in Phase II or III trials, are going to positively impact the DMD market. As per DelveInsight, Duchenne Muscular Dystrophy Market is anticipated to grow promisingly well from USD 266.06 Million as estimated in 2017 for the study period of 2017-30. Moreover, FDA’s flexibility in granting accelerated approvals to therapies for rare disease with high unmet needs shows the sheer dedication of the agency to bring relief to the patients suffering from the disease.