Synlogic’s dreams have gone up in smoke on the news that a pivotal phase 3 study of its lead phenylketonuria (PKU) drug is on track to miss its primary endpoint.
The Massachusetts-based biotech launched the 150-patient global Synpheny-3 trial of labafenogene marselecobac—which is designed to target and consume an amino acid called phenylalanine in the gastrointestinal tract—in June 2023. Top-line data had been expected in the first half of 2025.
As recently as early January, CEO Aoife Brennan sounded optimistic about the trial. In a Jan. 4 look ahead, Brennan suggested that the data monitoring committee review of initial study data was set to be a “key milestone” that would help ensure 2024 was another “momentous” year for the company that could usher in an expansion of the trial into adolescent PKU patients.
The committee’s review was indeed momentous for the company, but not in the way Brennan intended. Instead, they “indicated the trial was unlikely to meet its primary endpoint,” Synlogic revealed in a postmarket release Feb. 8. The decision was not based on concerns regarding the safety nor the tolerability of the drug, which is also known as SYNB1934, the biotech pointed out.
As a result, the company will cease operations and lay off more than 90% of its workforce this month. The remaining employees will be involved with discontinuing the Synpheny-3 study across trial sites and assisting in a “strategic review” of the company “to enhance shareholder value.”
Synlogic entered 2024 with cash, equivalents and short-term investments totaling $47.7 million.
“It is with a heavy heart that we share this news, and our resulting decision to end Synpheny-3,” said Brennan, who will also be stepping down. “Based on the program’s progress and data to date, we had expected the study to demonstrate the potential for SYNB1934 to provide an important new treatment option for those affected by PKU.”
The company had already slimmed down its pipeline and workforce in 2022, leaving its future heavily reliant on the success of labafenogene marselecobac.
PTC Therapeutics appeared to have more success last year in a phase 3 trial in PKU. However, the design of the study meant analysts remained unsure about the strength of PTC’s hand and whether its drug sepiapterin could rival BioMarin’s approved PKU drug Kuvan. Since then, PTC’s approval application for sepiapterin has been brushed aside by the FDA, which demanded an additional mouse study.