Vonvendi for von Willebrand disease

What is Vonvendi for von Willebrand disease?

Vonvendi (recombinant von Willebrand factor) is an approved protein replacement therapy that prevents and controls bleeding in patients with von Willebrand disease (VWD).

VWD is a bleeding disorder caused by a deficiency in functional von Willebrand factor (VWF). VWF is a protein that helps blood clot by sticking platelets together and by stabilizing and transporting another clotting protein called factor VIII (FVIII). Patients with VWD experience abnormally heavy bleeding for prolonged periods. Vonvendi is a VWD treatment that restores the level of functional VWF in a person’s body by delivering a lab-made version of the protein directly into the bloodstream.

Developed by Takeda Pharmaceuticals, Vonvendi recently received expanded approval from the U.S. Food and Drug Administration. In the U.S., it is now used as a prophylactic for all types of VWD in adults. Additionally, Vonvendi is used to manage bleeding episodes and prevent excessive bleeding during or after surgery in adults and children.

Therapy snapshot

Who can take Vonvendi?

Vonvendi is approved in the U.S. for the management of excessive bleeding during and after surgery and the treatment of bleeding episodes in adults and children with VWD. Additionally, it has approval in the U.S. as a routine prophylaxis to reduce the frequency of bleeding episodes in adults with VWD.

This therapy is contraindicated, or not recommended, in people who have had a life-threatening hypersensitivity reaction to Vonvendi or any of its components.

People with known risk factors for thrombosis, or the formation of blood clots inside blood vessels, should be closely monitored when receiving Vonvendi, as the treatment may increase the risk of thromboembolic events.

How is Vonvendi administered?

Vonvendi is given intravenously. Typically, its administration is done by a medical professional, but VWD patients can learn to infuse Vonvendi themselves with or without the help of a family member.

The dose and frequency of administration are specific to each patient. The treatment plan is determined by several factors, including weight, severity of VWD, location of bleeds, bleed intensity, desired FVIII concentration, and type of treatment (surgical, prophylactic, or on-demand).

Vonvendi in clinical trials

Data from six separate clinical trials supported Vonvendi’s approval for treatment and prophylactic use in VWD.

• In a Phase 1 clinical trial (NCT00816660), a single dose of Vonvendi was given to 31 patients with severe VWD. The data showed that Vonvendi was well-tolerated and safe. It also demonstrated that the therapy was able to stabilize FVIII already present in the patient’s body.
• A Phase 3 study (NCT01410227) in which Vonvendi was administered to adult patients to treat on-demand bleeding episodes. Treatment success was determined by comparing the estimated number of infusions needed to treat bleeding episodes to the actual number of administered infusions and was rated on a scale from 1 (excellent) to 4 (none). Clinicians reported that the efficacy of Vonvendi was excellent in 97% of the cases examined.
• A Phase 3 trial (NCT02283268) where researchers looked into the efficacy of Vonvendi in managing bleeds during elective surgical procedures. A total of 15 adult patients with severe VWD were analyzed; 10 had major surgeries and five had minor ones. Treatment efficacy was determined based on expected versus actual blood loss, transfusion requirements, and postoperative bleeding and oozing. Vonvendi’s efficacy was rated as excellent/good, and clotting was achieved in patients undergoing surgical procedures.
• Another Phase 3 trial (NCT02973087) tested the use of Vonvendi as a prophylactic for reducing the frequency of bleeding episodes in adult VWD patients. Results showed that Vonvendi effectively reduced spontaneous bleeding rates.
• A Phase 3b trial (NCT03879135) investigated Vonvendi for prophylactic use in adult and pediatric patients over a one-year period. The data showed that the treatment worked well in preventing and controlling bleeding events.
• Pediatric studies are still ongoing, with a Phase 3 trial (NCT02932618) testing the efficacy of Vonvendi when treating on-demand bleeds in children with severe VWD. So far, Vonvendi has been used to treat over 100 non-surgical bleeds in 18 children, with bleed control rated as excellent in 99% of the cases.

Vonvendi side effects

The most common side effects of Vonvendi include:

• Headache
• Vomiting
• Nausea
• Dizziness
• Generalized pruritus (itching)

Other possible side effects associated with Vonvendi include:

• Hypersensitivity, infusion-related reactions, and severe immune reactions can occur.
• Patients with known risk factors for developing blood clots are at a higher risk of experiencing dangerous clotting events. It is recommended that these patients be closely monitored and receive standard prophylactic care to manage this condition.
• Neutralizing antibodies, proteins that inhibit the function of recombinant VWF and FVIII, can develop, decreasing Vonvendi’s efficacy.