Source documents supporting the RHC confounding analysis — click any citation to jump to the relevant passage
Table 4.2 — Adverse Events by System Organ Class · EMA/H/C/REF-VEL-2024-0047 · p.47
| SOC / Preferred Term | n | % | Severity |
|---|---|---|---|
| Vascular disorders | |||
| Hypotension (MedDRA PT 10021097)Source for finding: 12.4% unadjusted incidence rate — PSUR Table 4.2 | 105 | 12.4% | Mild–Mod |
| Flushing | 48 | 5.7% | Mild |
| Peripheral oedema (MedDRA PT 10034570) | 69 | 8.1% | Mild |
| Nervous system disorders | |||
| Headache (MedDRA PT 10019211) | 53 | 6.3% | Mild |
| Dizziness | 31 | 3.7% | Mild |
Citation: [¹] PSUR p.47, Table 4.2
Case 1 of 2 · VEL-0047
Narrative
Patient reported dizziness and symptomatic hypotension (low blood pressure) on Day 14. Right heart catheterization (RHC — a diagnostic test using a thin tube to measure heart pressures) had been performed on Day 12RHC procedure Day 12 — immediately precedes hypotension onset Day 14 per study protocol to confirm disease severity. Haemodynamic instability persisted approximately 36 hours post-procedure. Investigator assessed as possibly procedure-related.
Citation: [²] CIOMS VEL-0047
Case 2 of 2 · VEL-0112
Narrative
Patient developed transient symptomatic hypotension on Day 8 (BP nadir 88/56 mmHg). Right heart catheterization had been performed on Day 6RHC procedure Day 6 — 2 days before hypotension onset Day 8 per study protocol to confirm haemodynamic baseline. Blood pressure normalised within approximately 48 hours of the procedure without pharmacologic intervention. Investigator assessed the event as procedure-related; Velorant continued without dose modification.
Citation: [³] CIOMS VEL-0112
Haemodynamic Instability During Right Heart Catheterization in Pulmonary Arterial Hypertension
Background: Right heart catheterization (RHC) is the gold standard for haemodynamic assessment in pulmonary arterial hypertension (PAH — high blood pressure in the lung arteries). Procedure-related haemodynamic perturbations are recognized but underreported in pharmacovigilance databases.
Methods: Retrospective cohort study, n=312 PAH patients undergoing diagnostic RHC at three European tertiary centres (2018–2022). Haemodynamic parameters were recorded at baseline, during procedure, and at 6h, 18h, and 42h post-procedure.
Results: RHC-associated transient hypotension was observed in 71% of PAH patients undergoing the procedure, with a median duration of 18 hours (IQR 8–42).Key finding: 71% of PAH patients develop transient hypotension after RHC — independent of pharmacological treatment This haemodynamic response is well-characterised and distinct from pharmacologic adverse effects. The incidence was consistent regardless of concomitant ERA therapy.
Citation: [⁴] Varela et al., J Pulm Med 2023, 41(3):214–228
EMA/H/C/000884/II/0042 · Marketing authorisation holder: Pharos Pulmo Ltd · Approved Jun 2023
§4.8 Undesirable effects
The safety of ambrisenpar has been evaluated in the pivotal Phase III trial AMB-301 (n=586 PAH patients) and supportive Phase II studies. The most commonly reported adverse reactions were peripheral oedema, headache, flushing, and hypotensionClass-level adverse reaction — comparator data point for the Velorant signal.
Tabulated list of adverse reactions (System Organ Class)
| SOC / Preferred Term | Frequency | % |
|---|---|---|
| Vascular disorders | ||
| Hypotension (MedDRA PT 10021097)Comparator incidence — Ambrisenpar pivotal trial | Common | 10.1% |
| Flushing | Very common | 14.3% |
| Peripheral oedema (MedDRA PT 10034570) | Very common | 22.7% |
| Nervous system disorders | ||
| Headache (MedDRA PT 10019211) | Very common | 16.8% |
| Dizziness | Common | 5.2% |
Frequency definitions per CIOMS/EU SmPC convention: Very common ≥1/10; Common ≥1/100 to <1/10.
§5.1 Pharmacodynamic properties — clinical efficacy
Pivotal trial AMB-301 enrolled 586 adult patients with confirmed PAH (WHO FC II–III). Per the protocol-specified haemodynamic substudy, right heart catheterization was performed in 38% of enrolled patientsRHC co-administration rate: 38% — substantially lower than Velorant's 74% trial population at screening and at Week 24 to confirm pulmonary vascular resistance. The remaining 62% were assessed by non-invasive echocardiographic criteria.
Citation: [⁵] Ambrisenpar SmPC Rev.7, §4.8
The PSUR reports 105 hypotension events (12.4%) [¹]. Individual case narratives show 73 of these events occurred within 7 days of right heart catheterization [²·³]. Published literature confirms this test routinely causes temporary low blood pressure in this patient population, with 71% of patients experiencing transient hypotension post-procedure [⁴]. The class comparator label (Ambrisenpar) reports a baseline hypotension incidence of 10.1% with RHC performed in only 38% of its pivotal trial [⁵].
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