Rare Daily Staff
The U.S. Food and Drug Administration issued a Complete Response Letter to Acer Therapeutics and its Swiss collaboration partner, Relief Therapeutics, regarding the New Drug Application (NDA) for ACER-001 for the treatment of patients with urea cycle disorders due to manufacturing issues.
Urea cycle disorders (UCDs) are the result of a severe dysfunction of the enzymes or transporters involved in the urea cycle that converts ammonia to urea. The condition results in an accumulation of toxic levels of ammonia in the blood and brain of patients. Elevated ammonia levels can cause coma and irreparable brain damage, potentially resulting in cognitive impairment, seizures, cerebral palsy, and death if untreated. UCD predominantly affects children either shortly after birth (about 50 percent) or, later at any age. Current treatment options, often associated with poor outcomes, include dialysis to lower ammonia levels, which must be conducted at specialized clinics, and liver transplantation.
ACER-001 (sodium phenylbutyrate) is being developed for the treatment of various inborn errors of metabolism, including UCDs and Maple Syrup Urine Disease (MSUD). ACER-001 is a nitrogen-binding agent in development for use as adjunctive therapy in the chronic management of patients with UCDs involving deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase, or argininosuccinic acid synthetase. ACER-001 is a polymer coated formulation that, when taken within 5 minutes, helps prevent the coating from dissolving. ACER-001 has been granted orphan drug designation by the FDA for MSUD.
The CRL indicates that the FDA cannot approve the NDA in its current form. The CRL states that the agency’s field investigator could not complete inspection of Acer’s third-party contract packaging manufacturer because the facility was not ready for inspection, and that the company should notify the agency in writing when this facility is ready for inspection.
The FDA did not cite any other approvability issues in the CRL pertaining to the NDA, nor request any additional clinical or pharmacokinetic studies be conducted prior to FDA approval. The FDA did provide one comment in the CRL requesting additional existing nonclinical information to be provided in the resubmission of the NDA.
Acer says it is actively collaborating with its third-party contract packaging manufacturer and cooperating with the FDA to address the FDA’s comments as soon as reasonably possible and currently intends to resubmit the updated NDA for ACER-001 (sodium phenylbutyrate) for oral suspension for the treatment of patients with UCDs in early-to-mid third quarter of 2022.
“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. We should be able to resubmit the NDA relatively quickly,” said Chris Schelling, CEO and founder of Acer. “We remain committed to bringing a new treatment option to patients in the U.S. with UCDs.”
Photo: Chris Schelling, CEO and founder of Acer