The aptamer rondoraptivon pegol improves von Willebrand factor (VWF) and factor VIII (FVIII) levels, high-molecular-weight (HMW) multimer patterns, and thrombocytopenia in type 2B von Willebrand disease (VWD), according to the results of a study published in Blood Advances. The findings suggest that rondoraptivon pegol may serve as a future prophylactic or treatment for patients with VWD.
Rondoraptivon pegol is a pegylated aptamer that enhances VWF/FVIII levels by decreasing their clearance. Researchers conducted a prospective phase 2 trial to evaluate the potential benefit of rondoraptivon pegol in patients with type 2B VWD (ClinicalTrials.gov Identifier: NCT04677803).
The study included 5 patients with type 2B VWD (3 men and 2 women), with a median age of 61 years. The patients were administered rondoraptivon pegol subcutaneously (3 mg) on days 1, 4, and 7 then weekly (6 to 9 mg) until day 28 of the study. VWD biomarkers were measured at baseline and weekly until day 56.
On day 35 (1 week after the final subcutaneous injection), the researchers found that rondoraptivon pegol had resulted in a 3-fold increase in median platelet counts (60×109/L vs 179×109/L; P <.001).
They also observed a 3-fold increase in median circulating VWF antigen (64% vs 143%; P <.001) and a 2-fold increase in FVIII activity levels (67% vs 134%; P =.002).
In thrombocytopenic patients (n=4), the researchers found that median plasma levels of VWF:GPIbM increased from 18% to a peak level of 72% (P <.001), VWF ristocetin cofactor increased from 17% to 48% (P <.001) and VWF collagen-binding activity increased from 50% to 100% (P =.002). They also demonstrated that HMW multimers patterns improved in all thrombocytopenic patients, with some attaining normalization of both intermediate and HMW multimers.
During washout of the drug, the team found that the biomarker improvements reversed, demonstrating causality. The researchers reported excellent local and systemic tolerability, with no serious or severe adverse events, and no adverse effects led to treatment interruption or discontinuation.
“In conclusion, rondoraptivon pegol addresses the underlying pathophysiology of thrombocytopenic type 2B VWD and significantly increases platelet counts and VWF/FVIII in such patients,” the researchers stated in their report. Limitations of the study included the small sample size and short trial duration.
Disclosure: This research was supported by Medical University of Vienna, which received financial support from Band Therapeutics Inc., a Guardian Therapeutics company. Please see the original reference for a full list of disclosures.
Ay C, Pabinger I, Kovacevic KD, et al. The VWF binding aptamer rondoraptivon pegol increases platelet counts and VWF/FVIII in type 2B von Willebrand disease. Blood Adv. 2022;6(18):5467-5476. doi:10.1182/bloodadvances.2022007805