PTC's plans crash into regulatory reality as FDA demands data on 2 candidates, delaying filing

PTC Therapeutics is keeping its regulatory teams busy. In its third-quarter results, the biotech reported pushback against its plans to seek approval for two molecules based on existing data—and saw its share price fall more than 20% in the wake of the update. 

The results featured news of a delay to the planned submission of sepiapterin in phenylketonuria (PKU). In May, PTC reported a phase 3 trial of sepiapterin met its primary endpoint. The biotech planned to file for FDA approval in the fourth quarter, but the agency torched that timeline at a recent meeting, informing PTC it needs to complete a 26-week nonclinical mouse study before seeking authorization.

PTC offered an explanation for why it has gotten this far without running the study, telling investors that the original plan was to seek approval under the 505(b)(2) pathway. That plan would have allowed the biotech to use data on a different reference drug to support its application. However, PTC changed to the 505(b)(1) pathway after buying the candidate from Censa Pharmaceuticals.

Analysts at William Blair told investors that PTC executives believe sepiapterin “is better suited for the Section 505(b)(1) pathway due to its differentiated mechanism.” The delay will push back the filing for FDA approval to the third quarter of next year, unless the agency allows PTC to submit the mouse data during the review process. If that happens, PTC could file in the second quarter of next year.

The analysts called the PKU delay an “unfortunate … minor setback.” The analysts continue “to view the results of the phase 3 APHENITY trial as supportive of approval” and see opportunities for the drug outside the U.S., where exposure to BioMarin’s rival drug Kuvan is lower. 

Investors appeared to be more concerned, sending PTC's stock down over 20% in premarket trading Friday to $19.01 from a Thursday closing price of $23.95.

Sepiapterin is one of several ongoing topics of conversation between PTC and the FDA. The biotech used its financial results to reveal that the regulator believes PTC will likely need to run a new confirmatory study of its Friedreich ataxia candidate vatiquinone before filing for approval. Vatiquinone failed a phase 3 trial in the disease earlier this year, but PTC identified upright stability as a data point that may support approval. 

In a written response to PTC, the FDA said it sees “the value of upright stability as a clinically meaningful endpoint,” according to the biotech, but believes a confirmatory study is needed. PTC has requested a meeting with the FDA to discuss the issues raised in the letter.

The biotech is also talking to the FDA about what it will take to resume U.S. enrollment in a Huntington's disease clinical trial. Enrollment is ongoing overseas but has been on hold in the U.S. for one year. The FDA told PTC “six months of clinical safety data demonstrating a similar favorable safety profile could support 12-month dosing.”