Regeneron has posted positive phase 2 data on baloncibart in postural orthostatic tachycardia syndrome (POTS), teeing the biotech up to start a potentially pivotal trial in the autonomic nervous system disorder in the first half of 2027.
The heart rate of POTS patients increases abnormally when they get up from sitting or lying down. Some symptoms, such as palpitations and dizziness, happen when patients stand up and lessen when they sit or lie down. But POTS is also associated with ongoing symptoms, including fatigue, exercise intolerance, cognitive difficulties, gastrointestinal symptoms and chronic pain.
Regeneron hypothesized that blocking NPR1 could alleviate symptoms by increasing the volume of blood in circulation. The biotech put that idea to the test in the phase 2 Pinnacle trial, which randomized 82 POTS patients to receive one of two doses of the anti-NPR1 antibody baloncibart or placebo.
At Day 8, people who received a single, 450 mg dose of baloncibart had an 11.4 beats per minute (bpm) lower change in heart rate from lying down to standing than their peers on placebo, meeting the trial’s primary endpoint. The difference between the arms was 7.4 bpm on Day 29. The 150 mg baloncibart dose beat placebo on Day 8, but the effect faded by Day 29.
George Yancopoulos, M.D., Ph.D., chief scientific officer of Regeneron, commented on the phase 2 study on the biotech’s third-quarter earnings call late last month. Improvements that “appear to be associated with durable restoration of intravascular volume” inform Regeneron’s belief that baloncibart “could be a game-changing treatment for a debilitating disease with significant unmet need,” Yancopoulos said.
Symptoms linked to standing improved on the 450 mg dose compared to placebo at Day 29, as did patients’ performance on assessments of physical functioning and activities of daily living. The 150 mg dose offered no obvious improvement over placebo.
On Day 8, Regeneron reported biomarker changes consistent with baloncibart’s expected effect on blood volume. Average standing systolic blood pressure increased on both doses, rising 8.7 mmHg to a mean of 118.8 mmHg on Day 29 in the 450 mg cohort.
Treatment-emergent adverse events (TEAEs) were more common on baloncibart than placebo, affecting 67.9% of patients on the 450-mg dose compared to 48.1% of people in the control arm. The TEAEs were mostly mild or moderate, and none of the adverse events led patients to stop treatment.
Based on the data, Regeneron plans to start a phase 3 clinical trial in the first half of next year. The potentially pivotal study could unlock an indication that Regeneron said affects between 500,000 and several million people in the U.S. Most POTS patients are women, and the condition has historically been underdiagnosed.
There are no FDA-approved treatments for POTS and few industry-sponsored clinical development programs. Argenx and CSL Behring ran clinical trials in patients who developed POTS after contracting COVID-19, but neither program is active.