Introduction: Desmopressin (DDAVP) is a cost-effective, safe, and efficacious treatment for bleeding in persons with von Willebrand disease (VWD) and mild hemophilia A. Desmopressin can be administered by subcutaneous and intravenous injection or as an intranasal spray. Global estimates suggest at least 210,000 bleeding events in persons with VWD and 13,000 events in persons with non-severe hemophilia A could be treated with desmopressin annually.

Intranasal desmopressin allows for self-administration, increasing convenience and accessibility while decreasing treatment burden. However, for many patients worldwide, availability is limited. The discontinuation of intranasal desmopressin acetate (Stimate) production in 2020 reduced treatment options for these patients. Persistent desmopressin shortages further restrict access in most geographic locations. Since 2021, a newly formulated desmopressin nasal spray manufactured by a registered 503b outsourcing facility has been available exclusively in the U.S. This study evaluates the efficacy of the newly formulated intranasal desmopressin compared with the discontinued intranasal desmopressin and subcutaneous desmopressin.

Methods:A retrospective analysis of desmopressin responsiveness was performed in persons with type 1 VWD (N=981) and mild hemophilia A (N=160) treated at the Indiana Hemophilia and Thrombosis Center. The intranasal desmopressin dose was 150 mcg for patients <50 kg and 300 mcg for >50 kg, and the subcutaneous dose was 0.3 mcg/kg. FVIII:C, VWF:Ag, and VWF:Act (VWF:RCo or VWF:GPIbM) were measured at baseline and 90 minutes after administration. For type 1 VWD, criteria for responsiveness (≥2x baseline VWF:Act; VWF:Act and FVIII ≥0.5 IU/mL) were based on ASH ISTH NHF WFH guidelines. This study met IRB criteria for exemption from full review.

Results: Among patients with type 1 VWD, those treated with subcutaneous desmopressin (N=32) had a younger mean age (6.0 vs. 19.4 years, p<0.001), lower weight (26.7 vs. 62.7 kg, p<0.001), and lower dose (0.3 vs. 4.6 mcg/kg, p<0.001) compared to patients who received newly formulated desmopressin (N=261). Patients in the newly formulated desmopressin cohort had a higher mean weight (62.7 vs. 56.1 kg, p=0.002) but not age or dose, compared with the intranasal desmopressin group (N=688).

Type 1 VWD patients who received newly formulated desmopressin had a mean fold-increase in VWF:Ag (2.44 ± 1.41) and VWF:Act (3.02 ± 1.56) that were not significantly different from intranasal desmopressin (VWF:Ag 2.47 ± 1.24, p=0.77; VWF:Act 3.04 ± 1.39, p=0.86) or subcutaneous desmopressin (VWF:Ag 2.25 ± 0.91, p=0.32; VWF:Act 2.75 ± 1.3, p=0.24). The mean fold-increase in FVIII:C was significantly elevated with newly formulated desmopressin (2.91 ± 1.37) compared to intranasal desmopressin (2.51 ± 0.99, p<0.001) but not subcutaneous desmopressin (2.52 ± 0.91, p=0.13). The overall responsiveness was 70.1% for newly formulated desmopressin, 76.9% for intranasal desmopressin (p=0.57), and 81.3% for subcutaneous desmopressin (p=0.29).

Among the patients with mild hemophilia A, those treated with subcutaneous desmopressin (N=6) had a younger mean age (3.1 vs. 21.5 years, p<0.001), lower weight (14.3 vs. 59.2 kg, p<0.001), and lower dose (0.3 vs. 4.5 mcg/kg, p<0.001) compared to newly formulated desmopressin (N=44). No significant differences were observed between the newly formulated desmopressin and intranasal desmopressin (N=110)-treated cohorts. Mild hemophilia A patients who received the newly formulated desmopressin had a mean fold-increase in FVIII:C (2.94 ± 2.35) that was not significantly different from intranasal desmopressin (3.43 ± 2.51, p=0.3) or subcutaneous desmopressin (4.14 ± 2.28, p=0.25).

Conclusions: Using the ASH ISTH NHF WFH criteria for desmopressin responsiveness and a non-inferiority margin of 15%, newly formulated intranasal desmopressin is non-inferior to the discontinued intranasal desmopressin acetate or subcutaneous desmopressin in type 1 VWD. These findings support the use of newly formulated desmopressin to manage bleeding in type 1 VWD and mild hemophilia A. Expanded availability of newly formulated intranasal desmopressin may improve access to safe and efficacious treatment worldwide.

This content is only available as a PDF.
2025
Sign in via your Institution