Sarepta Therapeutics will license global exclusive rights to BioMarin Pharmaceutical’s patent estate for the marketed Duchenne muscular dystrophy (DMD) treatment Exondys 51™ (eteplirsen) and all future exon-skipping treatments, under a $35 million-plus settlement of the companies’ patent dispute over the technology.

Under the companies’ agreement, BioMarin retains rights to convert that license to a co-exclusive right should it decide to proceed with its own exon-skipping therapy for DMD.

Just last year, BioMarin scuttled its DMD programs. BioMarin withdrew its Marketing Authorization Application (MAA) in Europe for its own candidate for DMD amenable to exon 51 skipping, Kyndrisa™ (drisapersen), in the face of an expected negative opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use. BioMarin acquired Kyndrisa when it bought Prosensa for up to $840 million.

BioMarin also halted clinical development of three Phase II first-generation follow-on products to Kyndrisa, the exon-skipping oligonucleotides BMN 044, BMN 045, and BMN 053. At the time, the company said it “will continue to explore the development of next generation oligonucleotides” to treat DMD.

Four months later in September, Sarepta received a double dose of good news concerning its DMD programs. On September 19, 2016, the FDA approved Exondys 51 despite recommendations by two advisory committees against approving the treatment and over objections from some administrators. Upon winning approval for Exondys 51, Sarepta obtained a Rare Pediatric Disease Priority Review Voucher (PRV) that it sold to Gilead Sciences in February for $125 million upfront.

A day later on September 20, the U.S. Patent and Trademark Office’s Patent Trial and Appeals Board (PTAB) sided with Sarepta in an interference proceeding against BioMarin related to exon-skipping patents. Sarepta had appealed an earlier PTAB decision favoring BioMarin claims in its U.S. Patent Application No. 14/198,992, which covered the use of exon 51 antisense oligonucleotides to treat DMD, and which was licensed from Academisch Ziekenhuis Leiden (AZL).

That decision included the cancellation of Sarepta's U.S. Patent No. 8,486,907, “Antisense oligonucleotides for inducing exon skipping and methods of use thereof,” held under license from the University of Western Australia—but did not affect Sarepta’s key composition of matter patent protection for Exondys 51, U.S. Patent No. 9,018,368, “Antisense oligonucleotides for inducing exon skipping and methods of use thereof,” whose assignee was also the University of Western Australia.

Milestone Payments and Royalties

In the settlement announced today, Sarepta agreed to pay BioMarin a one-time $35 million payment, plus unspecified regulatory and commercial milestone payments for exons 51, 45, 53, and possibly on future exon-skipping products.

Sarepta will also pay BioMarin royalties for compounds skipping exons 51, 45, and 53, and possibly on future exon-skipping products. Sarepta agreed to pay BioMarin 5% of net sales through the end of 2023 in the U.S., and 8% of net sales through September 30, 2024 in the E.U. and in other countries where certain BioMarin/AZL patents exist.

“Upon their effectiveness, these global license and settlement agreements provide Sarepta worldwide freedom to operate for Exondys 51 and our future exon-skipping products,” Sarepta president and CEO Douglas Ingram said in a statement.

“The resolution of these legal matters provides us with more certainty to fully focus our resources and energy on our crucial mission of developing innovative medicines to improve the lives of those impacted by DMD around the world.”

Exondys 51 generated $16.3 million in net product revenue during the first quarter, in what the company has called a successful launch of the treatment. Sarepta is set to release second-quarter results tomorrow.

Added G. Eric Davis, BioMarin’s evp and general counsel: “We are pleased to reach a global settlement and license agreement with Sarepta that fairly recognizes the important innovation by the Leiden University Medical Center and allows patients certainty that this issue will not create a barrier to access.”

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