Baloncibart reduces orthostatic heart rate and symptoms in Phase II POTS study

Regeneron has reported positive Phase II results showing that baloncibart reduced the excessive heart-rate increase associated with standing and improved symptoms in adults with postural orthostatic tachycardia syndrome.

The randomised, double-blind PINNACLE study evaluated single subcutaneous doses of baloncibart 150 mg and 450 mg against placebo.

Baloncibart is an investigational monoclonal antibody designed to block natriuretic peptide receptor 1, or NPR1, with the aim of increasing circulating blood volume.

At Day 8, the 450 mg dose reduced the change in heart rate from lying down to standing by 11.4 beats per minute compared with placebo.

The nominal p value was 0.0007.

The effect persisted through Day 29, when the 450 mg dose produced a 7.4 beats-per-minute reduction versus placebo, with a nominal p value of 0.0124.

The 150 mg dose also reduced orthostatic heart rate at Day 8, with a 9.5 beats-per-minute difference versus placebo.

However, this effect was not maintained at Day 29.

The study’s primary endpoint was the change in heart rate from lying to standing at Day 8.

Regeneron noted that no formal hypothesis testing was prespecified, meaning the reported p values should be considered nominal.

Patients receiving the 450 mg dose also showed improvements in symptoms and physical function at Day 29 as measured by the Living With POTS Questionnaire.

Orthostatic symptom scores improved by 12.9 points versus placebo, while physical functioning scores improved by 13.8 points.

Activities of daily living improved by 8.7 points versus placebo, although this comparison had a nominal p value of 0.1035.

The lower 150 mg dose did not show a clear overall improvement across these patient-reported domains.

Biomarker changes were also consistent with the proposed mechanism of NPR1 blockade.

Both doses increased NT-proBNP and reduced standing norepinephrine and haemoglobin at Day 8, changes Regeneron said were consistent with expansion of plasma volume.

Standing systolic blood pressure also increased in both active treatment groups.

By Day 29, mean systolic blood pressure had risen by 8.7 mmHg in the 450 mg group and by 5.4 mmHg in the 150 mg group.

Single doses of baloncibart up to 450 mg were generally well tolerated.

Treatment-emergent adverse events occurred in 48.1% of placebo patients, 66.7% of patients receiving 150 mg and 67.9% of those receiving 450 mg.

Most events were mild or moderate.

Two serious treatment-emergent adverse events were reported, including one case of headache in the 150 mg group and one case of syncope in the 450 mg group.

No adverse event led to treatment discontinuation.

Regeneron said the results support further development of baloncibart in POTS and plans to begin a potentially pivotal Phase III trial in the first half of 2027.

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Related Topics and Keywords

American Autonomic Society, autonomic disorders, baloncibart, Biopharma, Cardiovascular Disease, clinical trials, DeltaHR, dysautonomia, monoclonal antibody, natriuretic peptide receptor 1, neurology, NPR1, orthostatic heart rate, pharma news, Phase II, phase III, PINNACLE, plasma volume, postural orthostatic tachycardia syndrome, POTS, Regeneron