Peptide education
Selepressin
FE-202158 · FE 202158
Selepressin is an investigational peptide that activates the vasopressin V1a receptor. It was studied as a continuous intravenous vasopressor in adults with septic shock who were receiving norepinephrine.
In SEPSIS-ACT, the model-adjusted mean was 15.0 days alive and free of both ventilation and vasopressors during the first 30 days with selepressin, compared with 14.5 days on placebo. The difference was not statistically significant.
Overview
Quick answer
A selective receptor effect can explain a drug's blood-vessel action, but it does not establish an improvement in recovery or survival. The larger SEPSIS-ACT trial stopped for futility without meeting its primary endpoint.
What was selepressin designed to do?
It was studied as a selective V1a receptor agonist to raise blood pressure in septic shock. Researchers investigated whether that selectivity could improve outcomes in patients already receiving norepinephrine.
What happened in the larger trial?
SEPSIS-ACT randomized 868 adults, of whom 828 received study treatment. It stopped after the first part for futility. Ventilator- and vasopressor-free days and 90-day mortality were not significantly different from placebo.
Is selepressin an FDA-approved medicine?
An openFDA exact active-ingredient search for selepressin returned no match. Other names and jurisdictions require separate checks. FDA's substance record identifies the molecule but does not establish approval.
What safety events were reported?
The larger trial reported arrhythmias and cardiac, mesenteric and peripheral ischemia in both groups. The results do not establish the safety of another formulation or use outside the trial.
Evidence
Evidence snapshot
Model-adjusted days alive and free of ventilation and vasopressors in the first 30 days were 15.0 with selepressin and 14.5 with placebo. The observed group means were 14.2 and 14.3 days, respectively.
The adaptive trial compared three starting infusion regimens with placebo and stopped for futility at the end of its first part.
A phase 2a randomized study enrolled 53 patients and reported reduced norepinephrine use in one selepressin dose group. The larger trial did not confirm an improvement in its primary patient-centered outcome.
SEPSIS-ACT recorded cardiac arrhythmias and ischemic events in treated and placebo groups during critical illness.
An exact openFDA active-ingredient search for selepressin returned no match. A separate FDA substance record identifies its development-code alias.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Selepressin improves recovery from septic shock. | SEPSIS-ACT tested whether selepressin increased days alive and free from both mechanical ventilation and vasopressors. The result was not significantly different from placebo, and the study stopped for futility. | V1a receptor activation can cause blood-vessel constriction, but the study outcome measures a different question from receptor activity. | The trial did not demonstrate an improvement in the primary outcome. This result does not prove that every possible patient subgroup responds identically. |
| An early reduction in norepinephrine use guarantees a clinical benefit. | A small early trial reported lower norepinephrine use in one dose group. The larger trial subsequently found no significant difference in its primary ventilation-and-vasopressor-free outcome or key secondary mortality measure. | Norepinephrine use and patient-centered outcomes are different measures. | |
| V1a selectivity eliminates ischemic risk. | The larger trial reported cardiac, mesenteric and peripheral ischemia in both study groups. Those reports do not establish that an individual event was caused by the study drug. | The trial does not support treating receptor selectivity as a guarantee against ischemia. |
Bottom line
Main takeaway
Selepressin was studied in critically ill patients with septic shock. A large trial did not find the hoped-for improvement in time free from breathing machines and blood-pressure medicines.
A small early trial reported a dose-specific change in norepinephrine use. The larger randomized trial did not show a significant improvement in its main composite endpoint.
The adaptive study pooled three starting-dose regimens for its primary comparison. Deaths were assigned zero ventilator- and vasopressor-free days, and part two did not proceed after the futility assessment.
Identity
What it is
Selepressin, also identified as FE-202158, is a selective vasopressin V1a agonist. It was studied in an intravenous formulation for septic shock.
Septic shock can require medicines that narrow blood vessels to maintain pressure. SEPSIS-ACT tested selepressin in patients who still required norepinephrine after fluid treatment.
Use context
Routes, doses, and cycle patterns
SEPSIS-ACT compared three intravenous starting rates with placebo, then adjusted study infusions to hemodynamic targets in patients receiving norepinephrine.
Human studies and product labels
SEPSIS-ACT trial
- Purpose
- Days alive and free of ventilation and vasopressors
- Context
- Adaptive randomized placebo-controlled study
- Route
- Continuous intravenous infusion
- Amount
- Starting rates of 1.7, 2.5 or 3.5 ng/kg/min in separate regimens
- Frequency
- Infusion titrated to hemodynamic parameters
- Duration
- Median study-drug duration 37.8 hours
The trial enrolled adults with septic shock receiving norepinephrine. It stopped for futility at the end of the first study phase.
Early phase 2a trial
- Purpose
- Blood-pressure support and norepinephrine use
- Context
- Small randomized placebo-controlled study
- Route
- Continuous intravenous infusion
- Amount
- Selepressin dose groups included 1.25, 2.5 and 3.75 ng/kg/min
- Frequency
- Infusion during shock treatment
- Duration
- Until shock resolution or a maximum of 7 days
Only two patients received 3.75 ng/kg/min. One stopped infusion for possible safety reasons, and that dose group was discontinued. Results from one dose group do not establish a benefit in the larger trial.
What varies
- Dose units: trial infusion rates were expressed in nanograms per kilogram per minute.
- Trial population: patients had septic shock and were receiving norepinephrine; the study did not test outpatient use.
Research
Research evidence
Early dose-finding work reported a reduction in norepinephrine use for one selepressin group. The larger adaptive SEPSIS-ACT trial stopped for futility and did not find a significant difference in ventilator- and vasopressor-free days or 90-day mortality compared with placebo.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| SEPSIS-ACT | 868 randomized adults with septic shock, including 828 who received study treatment | Adaptive randomized double-blind placebo-controlled trial | Selepressin or placebo infused during norepinephrine treatment | Model-adjusted ventilator- and vasopressor-free days through day 30 were 15.0 versus 14.5; observed means were 14.2 versus 14.3. Model-adjusted 90-day mortality was 40.6% versus 39.4%; observed mortality was 41.7% versus 41.1%. Neither model-adjusted difference was statistically significant. | The trial stopped for futility before its planned second phase. Nonsignificant differences do not establish equivalence or exclude all subgroup effects. | Large randomized trial |
| Early phase 2a trial | 53 patients with early septic shock | Small randomized double-blind placebo-controlled dose-finding study | Intravenous selepressin or placebo with norepinephrine | One selepressin dose group had lower cumulative norepinephrine use than placebo over the reported study period. | Dose groups were small. One of two patients at 3.75 ng/kg/min stopped infusion for possible safety reasons, and that dose group was discontinued. The later larger trial did not show a significant difference in its primary outcome. | Early randomized evidence |
| FDA substance and approval records | US regulatory and chemical-identity context | Substance record and drug-approval database query | Selepressin and FE-202158 | The substance record identifies selepressin; an exact openFDA active-ingredient query for that name returned no match. | The substance record does not imply approval, and the search may miss other names, products, or jurisdictions. | Regulatory search and identity |
Use context
Reported use context
SEPSIS-ACT evaluated three continuous-infusion starting rates in adults with septic shock.
Study and label context
Starting rates of 1.7, 2.5 or 3.5 ng/kg/min were assigned in separate study regimens.
Study drug was titrated while patients received critical-care treatment.Cautions
Safety and unknowns
- SEPSIS-ACT reported cardiac arrhythmias in 27.9% of selepressin-treated and 25.2% of placebo-treated patients.
- Cardiac ischemia was reported in 6.6% versus 5.6%, mesenteric ischemia in 3.2% versus 2.6%, and peripheral ischemia in 2.3% versus 2.3%, respectively. These events occurred in patients with severe critical illness.
- The trial does not establish long-term safety or the safety of an untested preparation, dose or patient population.
- In the early phase 2a trial, one of two patients receiving 3.75 ng/kg/min stopped infusion for possible safety reasons, and that dose group was discontinued. The report did not establish causation.
Product quality
Product identity and quality
The trials used defined investigational intravenous preparations in monitored hospital settings.
Product identity
The FDA substance record identifies the molecule but is not proof that a particular preparation is equivalent to the trial product.
Mechanism
How it is proposed to work
Selepressin activates the vasopressin V1a receptor, which can narrow blood vessels. Its proposed selectivity was studied as a way to support blood pressure during septic shock.
A selective receptor mechanism does not establish improved survival or fewer days on ventilation and vasopressors. SEPSIS-ACT measured those clinical outcomes directly.
Details
Technical details
Sources
References
- 1.
PubMed Central. Selepressin in septic shock: the SEPSIS-ACT randomized trial
doi:10.1001/jama.2019.14607 PMID:31577035 NCT02508649
Full randomized trial report with model-adjusted and observed outcomes, infusion regimens and reported adverse events.
- 2.
Critical Care. Selepressin phase 2a randomized trial in septic shock
doi:10.1186/s13054-017-1798-7 PMID:28807037
Small early randomized study of selepressin infusion, norepinephrine requirements and the discontinued high-dose group.
- 3.
FDA: approval database. Drugs@FDA search page for selepressin
An openFDA exact active-ingredient query for selepressin found no match. The link opens the FDA search page, not a saved result; names and database coverage are limited.
- 4.
FDA: substance identity. FDA substance record for selepressin
Substance identity and FE-202158 alias; a substance identifier does not establish drug approval.