Selepressin

Septic shock is a dangerous drop in blood pressure during severe infection. Norepinephrine is the first-line drug for raising blood pressure, but it does not always work and its catecholamine (adrenaline-like) actions cause important side effects². Selepressin is a non-catecholamine vasopressor, meaning it raises blood pressure through a different pathway. It is a vasopressin analog that selectively activates the V1a receptor, building on earlier experimental work suggesting V1a-selective drugs might outperform vasopressin itself¹. It was also expected to limit the leaky blood vessels and swelling seen in sepsis².

In cultured human lung blood-vessel cells, it protected the cell barrier against four different disrupting agents, and that effect disappeared when the V1a receptor was silenced or blocked⁴. This has not been shown in patients.

The clinical evidence comes from intensive-care trials. A phase 2a trial in 53 people with early septic shock found that, at the main infusion rate studied, selepressin could largely replace norepinephrine while keeping blood pressure on target. At that rate, fluid balance was lower and more days were free of mechanical ventilation than with placebo¹. It was followed by SEPSIS-ACT, an adaptive phase 2b/3 trial that randomized 868 patients in Europe and the US^2,3. It was stopped for futility at the end of its first part. Ventilator- and vasopressor-free days within 30 days were 15.0 with selepressin versus 14.5 with placebo, and 90-day mortality, kidney-replacement-free days and ICU-free days did not differ². A later review concluded that few clinical data support its use⁵.

Selepressin is not approved by the FDA, and we found no approval by any other regulator. Its pivotal trial was terminated for futility⁶, and no ongoing trials are registered on ClinicalTrials.gov.

Human data come only from trials in critically ill patients. In SEPSIS-ACT, rates with selepressin and placebo were similar for cardiac arrhythmias (27.9% vs 25.2%), cardiac ischemia (6.6% vs 5.6%), mesenteric (gut) ischemia (3.2% vs 2.6%) and peripheral ischemia (2.3% vs 2.3%)².

In the phase 2a trial, adverse events at the main rate studied were similar to placebo. A higher-rate group was dropped after one patient's infusion was stopped over a possible concern¹.

1. Russell et al., Crit Care 2017PubMed
2. Laterre et al., JAMA 2019PubMed
3. Lewis et al., Ann Am Thorac Soc 2018PubMed
4. Barabutis et al., J Pharmacol Exp Ther 2020PubMed
5. Antonucci et al., Shock 2022PubMed
6. ClinicalTrials.gov: NCT02508649ClinicalTrials.gov