PTC Therapeutics finds itself in a regulatory whirlwind, as the latest third-quarter results reveal hurdles and setbacks impacting the biotech’s approval plans for two key molecules, leading to a more than 20% dip in its share price following the update.
One notable setback comes in the form of a delay in the submission of sepiapterin, intended for treating phenylketonuria (PKU). In May, PTC reported positive phase 3 trial results for sepiapterin, initially planning to seek FDA approval in the fourth quarter. However, during recent discussions with the agency, the FDA imposed a requirement for a 26-week nonclinical mouse study before granting authorization, pushing the submission timeline to the third quarter of the following year, unless the FDA permits submission of the mouse data during the review process, potentially allowing an earlier filing in the second quarter.
This unexpected delay has been attributed to PTC’s shift from the 505(b)(2) pathway, which initially allowed leveraging data from a different reference drug, to the 505(b)(1) pathway, prompted by the acquisition of the candidate from Censa Pharmaceuticals. PTC’s management believes that the 505(b)(1) pathway better aligns with sepiapterin’s distinctive mechanism. Although analysts view this PKU setback as a “minor setback,” they maintain optimism about the phase 3 APHENITY trial results, which support approval and hold promise for the drug, particularly in markets outside the U.S., where it faces lower competition from BioMarin’s rival drug, Kuvan.
However, investor response has been more cautious, resulting in a significant drop of over 20% in PTC’s stock price during premarket trading.
Sepiapterin isn’t the only topic of conversation between PTC and the FDA. The company disclosed that the regulator is likely to require a new confirmatory study for its Friedreich ataxia candidate, vatiquinone, before granting approval. Despite a phase 3 trial failure earlier this year, PTC identified an upside in stability data that could potentially support approval. The FDA acknowledges the clinical significance of this stability endpoint but believes a confirmatory study is necessary, prompting PTC to request a meeting with the agency to address these concerns.
PTC is also engaged in discussions with the FDA regarding the resumption of U.S. enrollment in a clinical trial for Huntington’s disease. While enrollment continues overseas, the U.S. portion has been on hold for a year. The FDA has indicated that “six months of clinical safety data demonstrating a similar favorable safety profile could support 12-month dosing.” This signals a pathway forward that PTC is eager to explore in collaboration with the regulatory authority.
