Post FDA Approval, Sarepta Wheels and Deals for Combo Duchenne Drugs

Xconomy Boston — 

Sarepta Therapeutics recently won the first FDA approval for a Duchenne muscular dystrophy drug, eteplirsen (Exondys 51). But the future for patients with the complex, progressive, fatal genetic disease is likely to lie in combinations of therapies, and that’s something Sarepta has clearly decided to pursue through deal-making.

For the second time in two weeks, Sarepta (NASDAQ: SRPT), of Cambridge, MA, has formed a pact with another biotech developing drugs for Duchenne. Last week, Sarepta and another Boston-area firm, Catabasis Pharmaceuticals (NASDAQ: CATB), inked a research deal to combine their two approaches to treating Duchenne. Now Sarepta is working with U.K.-based Summit Therapeutics, (NASDAQ: SMMT) on another group of combination Duchenne treatments.

Sarepta has paid Summit $40 million up front, and could shell out another $522 million overall, for partial rights to Summit’s experimental Duchenne drug ezutromid, which is currently in Phase 2 testing. Sarepta has also promised other downstream payments to Summit for partial rights to drugs, called utrophin-modulators, that work similarly to ezutromid. Specifically, Sarepta has acquired rights to ezutromid in Europe, Turkey, and the Commonwealth of Independent States. Sarepta has an option to grab rights in Latin America to ezutromid and Summit’s other utrophin drugs as well.

Starting in 2018, Sarepta will cover 55 percent of the costs for Summit’s utrophin drug research, according to a news release.

The two companies will host a joint conference call at noon to discuss the deal.

Eteplirsen’s FDA approval was controversial for many reasons, not the least of which was that the drug’s benefit to patients hasn’t actually been proven yet in clinical trials. The drug was approved on an accelerated basis after a scientific tug of war among FDA staffers, some of whom were wary to set a new standard for drug approvals. But that’s in the past now—Sarepta is running post-approval studies that will show whether the drug’s proposed benefit and seemingly benign safety profile is real.

One thing FDA scientists did agree on is that eteplirsen does, in fact, help patients produce dystrophin, the muscle-protecting protein that Duchenne patients lack. It’s not known yet how much dystrophin has to be made to really slow the march of Duchenne—which puts patients in wheelchairs by their teens and typically kills them from other complications by their mid 20s—but the fact that eteplirsen does help produce the protein, and that the drug is approved, means it can be used as the backbone of a potentially more effective combination of drugs. As Debra Miller, the CEO of nonprofit group CureDuchenne, said to Xconomy previously, “we will probably need a combination of therapies to treat the whole disease.”

Upon winning FDA approval of eteplirsen on Sept. 19, Sarepta’s shares skyrocketed. They went from $28.15 to $48.94 in a day, and have since climbed over $60. Sarepta raised $300 million on Sept. 22 by selling 5.02 million shares at $59.75 apiece, a huge win for a company that would have been in financial peril had eteplirsen been rejected. It is now putting that money to use, and not just in clinical trials, but deal-making to accumulate combination therapies.

Sarepta’s eteplirsen and the other, similar experimental drugs are known as “exon skippers.” They are RNA-based drugs that target an abnormality in part of the gene that makes the protein dystrophin and help patients skip past the faulty section of the gene so they can make enough dystrophin. Each of these drugs skip over a different section of the dystrophin gene, depending on which mutation to the gene is believed to be the cause of a patient’s Duchenne. Eteplirsen, for example, skips over exon 51 of the dystrophin gene; other drugs Sarepta has in clinical testing skip over exon 45 or 53. About 13 percent of Duchenne patients are believed to have a mutation amenable to eteplirsen treatment.

Last week, Sarepta struck a research deal with Catabasis to combine its exon-skipping drugs with experimental treatments from Catabasis that block a protein, NF-kB, implicated in inflammation and muscle degeneration in Duchenne patients.

In the latest deal, Sarepta is adding another combination. Summit’s drugs are meant to help boost the product of a different protein, utrophin, which, like dystrophin, is also involved in muscle repair. Sarepta CEO Ed Kaye said in the announcement that Summit’s utrophin drugs “may complement our current approach of exon skipping therapy.”

While each of Sarepta’s drugs are tailored to specific genetic subgroups of Duchenne patients, Summit’s utrophin-modulating drugs are meant for all types of Duchenne patients. Early data from Summit’s ongoing Phase 2 trial of ezutromid are expected in mid- to late 2017.

As of yet, it’s unclear how effective, if at all, Catabasis and Summit’s drugs will be. Still, in a research note, RBC Capital Markets analyst Simos Simeonidis called the Summit deal a smart move for Sarepta that removes a potential competitive threat for a small upfront price. It also makes Sarepta a more attractive takeover target for a company “interested in having access not only to the first commercial product for [Duchenne], but potential follow-on products in the space,” he wrote.