Santhera, Catalyst score FDA nod for Duchenne drug. Can they gain more indications for Agamree?

With the FDA approval of Agamree (vamorolone) to treat Duchenne muscular dystrophy (DMD), Santhera had cause for celebration late this week. While important, the company sees this indication as a launchpad for potential future approvals.

Now, the Swiss company is anxious to see how many disorders the first-in-class corticosteroid can treat.

As a dissociative steroid, vamorolone can retain the properties that provide steroids with efficacy while evading other properties that cause detrimental side effects, according to Santhera. This unique mechanism of action could make vamorolone an option for a variety of inflammatory conditions that are tamed by steroids but can also leave patients overwhelmed by side effects.

“There’s a list of things that—as longer-term data comes out—we’re hoping to come to market with and say, ‘Here’s a molecule that gives you the anti-inflammatory benefits of steroids, which are very well documented in Duchenne, but because it’s better tolerated and because we avoid some of these life-changing side effects, you can actually stay on a higher dose for longer,’” Shabir Hasham, M.D., Santhera’s chief medical officer, said in an interview.

Among the conditions vamorolone could potentially treat are asthma, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis and other rare genetic diseases like DMD, the company figures. As it develops vamorolone, Santhera will focus on the rare diseases first.

One of the best things about the approval, according to Santhera’s CEO Dario Eklund, is the funding it will provide to investigate Agamree’s potential.

“By the time I’m retired and looking back at this venture, I don’t think that Duchenne will be the biggest indication generating revenue for the drug. I think there’s going to be a lot of other indications and bigger indications,” Eklund said.

Catalyst Pharmaceuticals holds the commercial rights to the treatment and potential future indications in North America, paying $231 million, including $90 million upfront, for those rights in June. The deal allowed Santhera to pay off debt and extend its runway to the first quarter of 2025.

Catalyst expects to launch Agamree in the first quarter of next year, it said.

In 2022, the company also sold the commercial rights for all indications of the drug in China to Sperogenix for $124 million.

Santhera now turns its attention to Europe. Earlier this month, Europe’s Committee for Medicinal Products for Human Use recommended (PDF) the drug for approval. The company expects a decision from the European Commission by the end of this year, with the U.K. following suit per mutual recognition procedure.

The company is forecasting the drug's sales potential in Europe to exceed 150 million euros ($158 million) in five years, Eklund said. By that time, Santhera and Catalyst hope to already have new indications approved. The two companies will share the cost of running clinical trials, Eklund said.

“We’ve now shown safety and efficacy in a pediatric population, so we believe and hope that the FDA will agree to take it to phase 2b pivotal studies in these other indications,” Eklund said. 

Agamree is an oral suspension treatment taken daily with dosage determined by the weight of the patient. The FDA nod covers patients age 2 and older.

The approval was backed by results from a phase 2b trial, coupled with safety data collected from three open-label studies, which spanned up to 48 months of treatment. Compared with standard-of-care corticosteroids, vamorolone showed comparable efficacy in a time-to-stand velocity test. Data also indicated a reduction in adverse events, with improved bone health, growth trajectory, weight management and behavior.

Since it was granted orphan-drug and rare pediatric disease designations in DMD, Agamree will receive an additional seven years of exclusivity. Santhera expects patent protection to last through 2040 in the U.S. and 2035 in Europe.

ReveraGen, a Maryland company that runs under a venture philanthropy model and specializes in DMD treatments, developed vamorolone. In 2016, Actelion picked up an option on the drug, but, when the company was reborn later as Idorsia, it sold the rights of vamorolone to Santhera.

Upon Thursday’s approval, Santhera received a milestone payment of $36 million from Catalyst, but the company turned $10 million of it over to Idorsia and $16 million to ReveraGen through prior licensing arrangements.

DMD is the most common form of muscular dystrophy. It is a genetic condition in which patients cannot produce dystrophin protein, which is crucial to muscle function. It causes the loss of ambulatory ability and respiratory failure.

Those with DMD rarely live for more than 25 years. Of the roughly 12,000 DMD patients in the U.S., about 70% are treated with steroids, Catalyst said.

There are other treatments for DMD, but none should affect the uptake of Agamree, according to Santhera. Over the last four years, NS Pharma has gained approval for Viltepso, while Sarepta Therapeutics has scored nods for Exondys 51 and gene therapy Elevidys, which is priced at $3.2 million.

“They’re all these sophisticated modalities with exon skippers or gene therapies coming in. They always come in addition to steroids, so they’re not replacing steroids,” Eklund said. “We’re actually quite hopeful that over time, the standard of care for all these more sophisticated modalities will be to prescribe them in combination with vamorolone.”