Acer Therapeutics Readies for FDA Ruling on UCDs Drug

 On June 5, the U.S. Food and Drug Administration is expected to decide the fate of Acer Therapeutics’ experimental treatment for Urea Cycle Disorders (UCDs), ACER-001. It’s a place that Chief Executive Officer Chris Schelling has been before with another experimental drug but this time he’s hoping for a different outcome.

Three years ago, Schelling and Acer received a Complete Response Letter from the regulatory agency for Edsivo, a treatment in development for vascular Ehlers-Danlos syndrome (vEDS), the most severe subtype of a group of hereditary diseases of the connective tissue. Although the results were not what Schelling had hoped for, he told BioSpace that he is hopeful the path for ACER-001 in UCDs will be a bit smoother and more straightforward given the clinical history of the drug (sodium phenylbutyrate), a novel formula of an existing treatment for UCDs. In clinical studies, ACER-001 demonstrated comparable efficacy to Horizon Pharma’s Buphenyl, one of the two approved treatments for the disease.  

But, Schelling noted a distinct advantage ACER-001 has over Buphenyl, a distinctly improved palatability for UCDs patients. Schelling described the flavor of Buphenyl as that of vomit or rancid butter. Because many UCDs patients are children who regularly take the oral treatment, Schelling said the horrid flavor leads to low compliance among patients.

There is a second available treatment for UCD, Ravicti, which is also marketed by Horizon Pharma. That drug is mostly flavorless, Schelling said. But the big catch with Ravicti is that is has an annual cost of nearly $1 million. In comparison, Buphenyl costs about $350,000 per year. Schelling said patients have a toss-up between selecting a drug that costs $1 million per year or a drug that tastes like vomit.

In contrast to those options will be ACER-001, which is far more palatable in flavor than Buphenyl, Schelling said. Although Acer has not released any pricing details, Schelling said the annual cost will “be at a premium to Buphenyl and a significant discount compared to Ravicti.”

For potential approval of ACER-001, Schelling said the clinical data associated with the New Drug Application will have to demonstrate safety and efficacy that is comparable to Buphenyl. If ACER-001 is approved on June 5, he anticipated the drug would be available for the approximately 800 patients it would serve in the second half of the year.

A former BioMarin executive, Schelling said he and his chief medical officer, Adrian Quartel, who also came to the company from BioMarin earlier this year, are quite familiar with the clinical practices that service these UCDs patients. The Acer commercial teams will be able to inform the treating physicians about ACER-001 if it is approved and explain the advantages of shifting Buphenyl patients to their drug.

“We’ve had relationships with these clinics for a long time. We have a good opportunity to move patients over to our drug. Everything is teed up and ready to go on manufacturing,” he said.

UCDs are a group of disorders caused by genetic mutations that result in a defective urea cycle. Those who are afflicted with this disease are unable to expel excess accumulation of ammonia in the bloodstream, a condition known as hyperammonemia. Those high levels of ammonia can lead to brain damage and death, Schelling said. While the disease is genetic, there are cases of late-onset UCDs, which affect about 25% of the known patient population, he added.

In addition to UCDs, Acer is also developing ACER-001 for a condition known as Maple syrup urine disease, a condition where the body cannot process certain amino acids, which cause a build-up of substances in the blood and urine. The disease is so-called due to the sweet smell of the urine in infants who have the disease.

Our goal is to try to provide treatments for underserved populations as quickly as possible,” Schelling said. In addition to ACER-001, that goal also applies to ACER-801, an experimental treatment for Vasomotor Symptoms and Edsivo.

Although Edsivo (celiprolol) was rejected by the FDA three years ago, Acer is continuing to aim its resources at the drug. Acer gained Edsivo (celiprolol) through a licensing deal with Sanofi. The drug has been approved for use with vEDS patients in Europe and other locations. Schelling recognized that the trial design that supported the initial NDA for Edsivo was not as strong as it could have been for regulatory approval. Acer has continued to focus on Edsivo’s clinical development and won Breakthrough Therapy designation in April. The company is planning a Phase III study that could potentially bring it back before the agency in a few years. The trial design is still being finalized but Schelling expressed confidence that the study will continue to demonstrate efficacy in vEDS patients and provide a potential treatment option for the approximately 2,000 patients in the U.S. who face this horrible disease.

“It’s really a devastating disease where not enough collagen is produced that causes fragility in blood vessels,” Schelling said. He noted that this fragility can lead to aneurysms and spontaneous vascular ruptures, which can all be life-threatening.

He hopes a study will be greenlit by the FDA and can begin later this summer. The trial is estimated to take up to four years due to the number of vascular incidents among patients in the trial.

“We are committed to developing a treatment for this patient population,” he said.

https://www.biospace.com/article/acer-therapeutics-readies-for-fda-ruling-on-ucds-drug-/