https://orcid.org/0000-0003-3180-3570
Key Points
The factor D inhibitor vemircopan led to a clinically meaningful increase in hemoglobin in patients with PNH during this phase 2 trial
Despite this trial meeting its primary endpoint, concerns regarding intravascular hemolysis emerged, leading to early trial termination
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, complement-mediated hematologic disease. We present the results of a phase 2, open-label clinical trial of vemircopan monotherapy in patients with PNH (NCT04170023) to explore whether inhibiting the complement alternative pathway via factor D is safe and effective for patients with PNH. Adults (≥18 years) with PNH who were treatment-naive, switched from eculizumab with hemoglobin (Hgb) <10 g/dL, or rolled over from danicopan monotherapy (ACH471-103 trial; NCT03181633) were enrolled. The trial comprised a 60-day screening period, 12-week treatment period, and 148-week long-term extension. Participants received vemircopan 120 mg twice daily (bid), with potential escalation to 180 mg bid. The primary endpoint was change from baseline to week 12 in Hgb (g/dL). Safety endpoints included treatment-emergent adverse events (TEAEs) and serious AEs. Twenty-nine participants were enrolled (treatment-naive, n=12; eculizumab-switch, n=11; danicopan-rollover, n=6); all completed the 12-week treatment period, and 1 danicopan-rollover participant completed the long-term extension. Clinically meaningful improvements from baseline to week 12 in mean (SD) Hgb (change of ≥2 g/dL) were reported in the treatment-naive (3.6 [1.5]) and eculizumab-switch (3.3 [2.0]) cohorts and maintained through the end of the trial. Eighty-two breakthrough intravascular hemolysis (BT-IVH) events in 25 participants were reported. Twenty-eight participants reported TEAEs, and 14 reported serious AEs; most were unrelated to vemircopan. No deaths occurred. This trial evaluating vemircopan monotherapy in patients with PNH met its primary efficacy endpoint; however, concerns regarding BT-IVH risk and suboptimal, inconsistent control of IVH emerged, leading to early trial termination. This trial was registered with ClinicalTrials.gov (NCT04170023) and EudraCT (2019-003830-17).
