The von Willebrand Factor (VWF)-binding aptamer rondaptivon pegol extends the half-life of substituted factor VIII (FVIII) and increases endogenous FVIII levels in patients with hemophilia A, according to research published in Blood.
Researchers conducted a phase 2 trial to evaluate the safety, pharmacokinetics, and pharmacodynamics of rondaptivon pegol in adult patients with hemophilia A (ClinicalTrials.gov Identifier: NCT04677803). The primary endpoint was safety of subcutaneous rondaptivon pegol injections and effects on FVIII levels.
Patients received an initial fixed dose of rondaptivon pegol (3 mg on days 0 and 4) followed by weekly doses (2-9 mg) until day 28.
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A total of 19 patients (median age, 42 years; range, 20-62; 78.9% men and 21.1% women) received subcutaneous injections of rondaptivon pegol. Most patients had severe (47%) or mild (42%) hemophilia A, and 11% had moderate disease.
The investigators reported rondaptivon pegol was well tolerated and showed a good safety profile, with no clinically relevant adverse events (AEs). A total of 13 treatment-related AEs occurred, with 4 possibly drug related AEs occurring in patients with severe disease and 1 possibly drug related AE occurring in a patient with nonsevere disease. All AEs were mild or moderate.
The team found that 6 doses of rondaptivon pegol increased the half-lives of 5 different FVIII products approximately 3-fold from a median of 10.4 hours to 31.1 hours (range, 20.8-56.0) in patients with severe hemophilia A.
In patients with nonsevere hemophilia A, the investigators found rondaptivon pegol increased median endogenous FVIII levels approximately 2-fold from 19% at baseline to 41% at 1 week after the last injection (P <.0001). FVIII increased from 22% to 48% in patients with mild hemophilia A and from 3% to 7.5% in those with moderate hemophilia A.
“Rondaptivon pegol could be used to enable once-weekly substitution therapy in severe hemophilia A or as prophylaxis in nonsevere hemophilia A,” the investigators concluded in their report. The primary limitation of the study was the small sample size.
Disclosure: This research was supported by Band Therapeutics, a Guardian Therapeutics company. Please see the original reference for a full list of disclosures.
Reference
Ay C, Kovacevic KD, Kraemmer D, et al. The von Willebrand factor-binding aptamer rondaptivon pegol as a treatment for severe and nonsevere hemophilia A. Blood. 2023;141(10):1147-1158. doi:10.1182/blood.2022016571
