FDA rebuffs Acer and Relief's urea cycle disorder prospect over manufacturer's unfinished inspection

Acer Therapeutics has hit a regulatory speed bump on its quest to advance a taste-masked alternative to existing urea cycle disorder (UCD) meds like Buphenyl. Still, the company and its production partner should be able to sort things out “relatively quickly,” Acer’s chief executive said.

Thanks to an incomplete contract manufacturer inspection, the FDA has slapped down Acer’s application for sodium phenylbutyrate for oral suspension in UCD, the company and its U.S. commercial partner Relief Therapeutics said this week.

An agency field investigator was unable to inspect a third-party production partner for the med, which also goes by the name ACER-001, according to the FDA’s complete response letter. The contract manufacturer’s facility “was not ready for inspection,” the FDA states in its letter, as quoted by Acer.

Now, ACER-001’s bid to treat patients with UCD—an inherited disease where ammonia builds up in the blood because of faulty or missing liver enzymes—is on hold until the inspection can be finished. The FDA has asked for written notification once the facility is ready for inspection, according to the CRL.

There weren’t any other approval issues at play in the FDA’s letter, Acer explained in a release. The regulator didn’t request any studies before a potential approval. The FDA did, however, ask for “additional existing nonclinical information” in the drug’s resubmission, though the CRL pointed out that this was “not an approvability issue,” Acer said.

Now, Acer and its unnamed manufacturing partner are already on the case, with the aim to tackle the FDA’s comments “as soon as reasonably possible,” the company said. Acer hopes to resubmit an updated new drug application for ACER-001 for oral suspension in UCD in the “early-to-mid” period of 2022’s third quarter.

“While the outcome of the NDA review was not what we had hoped for, multiple rounds of labeling negotiations have already been conducted to date and we believe the recommendations raised by FDA can be appropriately addressed,” Acer CEO and founder Chris Schelling said in a statement. “We should be able to resubmit the NDA relatively quickly,” he added.

Should it eventually clinch a UCD green light, ACER-001, which is also in development for maple syrup urine disease (MSUD), would have to contend with existing treatments like Horizon Therapeutics’ Buphenyl. Acer’s med is a polymer-coated formulation of the same active ingredient in Buphenyl, sodium phenylbutyrate, which, when taken within five minutes, helps prevent the coating from dissolving, Acer says.

Acer’s drug is designed to lack a bitter taste and dissolve quickly in the stomach, too, which could eliminate one source of noncompliance with current UCD meds.

Buphenyl, for instance, must be taken with food. By improving the odor and taste of sodium phenylbutyrate, Acer is angling to enable its formulation to be taken in a fasted state. The maximum concentration of phenylbutyrate achieved by ACER-001 was higher when given in a fasted state, results from a 2020 bridging study show.

Horizon’s med Buphenyl, for its part, brought home $7.9 million in U.S. sales last year, Horizon said in its 2021 annual report. UCD affects about one out of every 8,200 births in the U.S., the American Association for Clinical Chemistry says. Worldwide, the disease is approximated to crop up in one out of every 35,000 people, two-thirds of whom suffer neonatal symptoms, the association says.