Novel Factor Replacement Therapies for VWD
Recently, 2 novel factor replacement therapies were approved for treatment of patients with VWD. The first is a human recombinant product, vonicog alfa, that was approved for use in the United States; the second is a plasma-derived concentrate product approved for use outside the United States. These products may reduce exposure to FVIII, allowing clinicians to manage the primary causes of VWD and tailor treatment to the patient’s individual bleeding phenotype.
“This [could] allow for more frequent dosing of VWF if needed, without the risk of accumulation to supranormal levels of FVIII,” Dr Peyvandi and colleagues wrote.
In certain patients with VWD, desmopressin may be an appropriate treatment choice. However, desmopressin is only effective if sufficient amounts of functional cellular VWF are available. As a result, the clinical efficacy of desmopressin may be limited or nonexistent in patients with severe forms of type 1 VWD, as well as those with type 2 or type 3 VWD. Other concerns include the occurrence of adverse events, such as hyponatremia, which may also limit use.
“Hematologists may prefer VWF replacement over desmopressin in certain clinical situations (eg, childbirth, major surgery, children younger than 2 years, elderly patients with a history of heart disease, and patients with extensive comorbidities),” the reviewers wrote.
Limitations and Future Directions
Currently, factor replacement therapies are the primary treatment modality for patients with VWD who are unresponsive to desmopressin or other drug therapies. However, the current body of literature lacks prospective studies to effectively compare the various factor replacement therapies available. Additional concerns include which assays are best to monitor clinical responses in patients treated with these agents.
“There is currently no standardized approach to factor replacement therapy in VWD,” the reviewers explained. However, they noted that “the more recently available factor replacement therapies may provide flexibility to control the amount of FVIII administered along with VWF, allowing for individualization of therapy.”
1. Peyvandi F, Kouides P, Turecek PL, et al. Evolution of replacement therapy for von Willebrand disease: from plasma fraction to recombinant von Willebrand factor [published online April 3, 2019]. Blood Rev. doi:10.1016/j.blre.2019.04.001