Manufacturing Issues Trip up Acer, Relief in NDA Quest

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Massachusetts-based Acer Therapeutics, together with its Swiss partner Relief Therapeutics, announced Tuesday that the U.S. Food and Drug Administration has denied the companies’ New Drug Application for ACER-001 (sodium phenylbutyrate), which is being developed for the treatment of urea cycle disorders.

In its Complete Response Letter (CRL), the FDA cited issues regarding a third-party packaging manufacturer as the reason for the non-approval.

“[The FDA’s] field investigator could not complete inspection [of Acer’s third-party contract packaging manufacturer], because the facility was not ready for inspection,” the CRL read. “Satisfactory inspection is required before [the NDA] may be approved." The regulator requested that Acer and Relief notify it when the facility is ready for inspection.

Encouragingly, the regulatory body found no other issues, especially regarding the drug itself. The FDA requested no additional clinical or pharmacokinetic data from Acer and Relief. It did, however, ask that the companies include existing nonclinical information in their resubmission of the NDA, though the agency pointed out that this was “not an approvability issue.”

Acer stated that it is actively collaborating with both the third-party packaging manufacturer and the FDA to quickly resolve the CRL. Though today’s denial is a setback for Acer and Relief, the pharma partners expect to resubmit their application in the third quarter of this year.

ACER-001 is a nitrogen-binding agent and is meant to be used as a supplemental therapy for the chronic management of inborn errors of metabolism such as urea cycle disorders and maple syrup urine disease. In terms of formulation, the drug candidate consists of a core center, a layer of active sodium phenylbutyrate and an outer coating that helps mask the bitter taste of the active drug. ACER-001 has not been granted approval for any indication by any regulatory agency.

Acer and Relief first submitted their NDA for ACER-001 in October 2021, following promising results from two bioequivalence trials, which showed that their drug candidate had a similar relative bioavailability profile as the reference drug Buphenyl (sodium phenylbutyrate).

At the time, the FDA set a Prescription Drug User Fee Act target action date of June 5, 2022, eight months after NDA submission. Though the regulatory agency can typically arrive at a decision within its assigned timeframe, deadlines aren’t set in stone. In some cases, such as with ACER-001, the review process may need to be extended due to the need for more data or other unexpected roadblocks.

“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,” Chris Schelling, CEO and founder of Acer, said in a statement. “We remain committed to bringing a new treatment option to patients in the U.S. with UCDs.”