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Velorant — Hypotension Signal Assessment
Draft prepared by iSAT · Data lock: October 2024 · EMA/H/C/REF-VEL-2024-0047
A disproportionality signal for hypotension (preferred term: Hypotension, MedDRA PT 10021097) was identified during routine PSUR (Periodic Safety Update Report — a regulatory document summarising safety data over a defined period) review. The unadjusted incidence rate of 12.4% [¹] PSUR p.47"Hypotension: n=105 (12.4%)" — Table 4.2, PSUR Q4 2024, p.47 appears elevated relative to the endothelin receptor antagonist (ERA — a class of drugs that block endothelin receptors, reducing blood vessel constriction in the lungs) class average of 10.4% [⁵] Ambrisenpar SmPC"Hypotension reported in 10.1% of patients in pivotal trial; RHC co-admin 38%", representing an apparent 19% excess.
Cross-document analysis by iSAT identified a statistically significant temporal clustering pattern: 70% of events (n=73/105) occurred within 7 days of right heart catheterization (RHC — a diagnostic test using a thin tube to measure pressures in the heart and pulmonary arteries, the gold standard for confirming PAH) procedures [²] CIOMS VEL-0047"RHC performed Day 12… hypotension Day 14… possibly procedure-related"[³] CIOMS VEL-0112"RHC Day 6… transient hypotension Day 8… normalised within 48h". RHC was administered to 74% of Velorant trial participants per protocol.
Published literature confirms that RHC-associated transient hypotension occurs in 71% of PAH (pulmonary arterial hypertension — high blood pressure in the arteries supplying the lungs) patients undergoing the procedure, with a median duration of 18 hours (Varela RM et al., J Pulm Med 2023, 41(3):214–228) [⁴] Varela et al. 2023"RHC-associated transient hypotension observed in 71% of PAH patients, median 18h".
Removing the 73 procedure-associated events, the estimated drug-attributable hypotension rate is approximately 3.8%, which is consistent with ERA class expectations (3–5%) and does not represent a disproportionate safety signal.
No label change is warranted at this time. The confounding role of RHC co-administration should be documented in the Risk Management Plan (RMP — a regulatory document outlining known risks and how they are managed) and communicated to investigators. Routine monitoring per current protocol is sufficient.
Draft generated by iSAT. Review and approve before submission. All citations traceable to source documents in the Evidence Panel.