Septerna Inc. announced the immediate discontinuation of its Phase I clinical trial evaluating SEP-786, the company's lead candidate for hypoparathyroidism treatment, following serious safety concerns observed in study participants. The decision came after two severe cases of elevated unconjugated bilirubin were reported in the highest dose cohort during the multiple ascending-dose (MAD) portion of the trial.
The safety signal, which emerged during routine monitoring of healthy volunteers, prompted swift action from the company to protect participant safety. Elevated unconjugated bilirubin levels can indicate potential liver dysfunction or other metabolic disturbances, raising significant concerns about the drug's safety profile at higher doses.
The trial's termination represents a significant setback for Septerna's development program in hypoparathyroidism, a rare endocrine disorder characterized by insufficient parathyroid hormone production. The condition affects approximately 200,000 people in the United States and can lead to serious complications including seizures, cardiac arrhythmias, and kidney problems if left untreated.
Market Impact and Company Response
The market reaction to the trial's termination was immediate and severe, with Septerna's stock price plummeting by as much as 68% on February 18. This sharp decline reflects investor concerns about the company's pipeline and the potential implications for its drug development strategy.
Clinical Development Implications
The termination of SEP-786's development program highlights the critical importance of safety monitoring in early-phase clinical trials. While Phase I studies in healthy volunteers are designed to establish safety and tolerability, they can reveal unexpected adverse effects that necessitate program termination, even for promising therapeutic candidates.
The development setback also underscores the ongoing challenges in developing novel treatments for hypoparathyroidism, where current therapeutic options remain limited. Patients with this condition typically rely on calcium and vitamin D supplementation, with few targeted treatment alternatives available.
