Date: 2017-06-22
Type of information: Positive opinion for the granting of a Market Authorisation in the EU
Product name: Vonvendi®/Veyvondi®- BAX111
Compound: recombinant von Willebrand Factor -vonicog alfa
Therapeutic area: Hematological diseases - Genetic diseases - Rare diseases
Action mechanism:
- protein/replacement therapy. Patients with Von Willebrand disease have a deficiency or dysfunction of Von Willebrand factor, a blood protein required for proper clotting. Because of this, the blood does not clot properly, which may result in heavy menstrual periods, easy bruising, or frequent nose bleeds. Vonvendi®/Veyvondi® is a replacement therapy produced and formulated without the addition of any exogenous raw materials of human or animal origin, resulting in a product that contains only trace amounts of FVIII.
Company: Baxalta (USA - IL) now Shire (UK - USA)
Disease: Von Willebrand disease
Latest news:
- • On June 28, 2018, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the granting of marketing authorization in the European Union (EU) for Veyvondi® [vonicog alfa, recombinant von Willebrand factor] (rVWF), for the treatment of bleeding events and treatment/prevention of surgical bleeding in adults (age 18 and older) with von Willebrand disease (VWD) when desmopressin (DDAVP) treatment alone is ineffective or not indicated. Veyvondi® will be the first and only recombinant von Willebrand Factor (rVWF) treatment in the EU for von Willebrand disease (VWD) that specifically addresses the primary deficiency or dysfunction of von Willebrand Factor (VWF) while also allowing the body to restore and maintain adequate Factor VIII (FVIII) plasma levels.
- The CHMP submission was based on outcomes from three clinical trials of a total 80 patients with VWD exposed to Veyvondi®. These include a Phase 1 multicenter, controlled, randomized, single-blind, dose-escalation study of the safety, tolerability and pharmacokinectics (PK) of rVWF:rFVIII in subjects 18 to 60 years of age with severe VWD; a Phase 3 multicenter, open-label study to assess the PK, safety and efficacy of rVWF:rFVIII and rVWF in the treatment of bleeding episodes in adult subjects with severe VWD; and a Phase 3, prospective, open-label, uncontrolled, non-randomized, international multicenter study to assess the hemostatic efficacy and safety of rVWF with or without rFVIII in 15 adult subjects with severe VWD undergoing major, minor, or oral elective surgical procedures.2
- • On June 22, 2017, Shire announced that the European Medicines Agency (EMA) validated the Marketing Authorization Application (MAA) for Veyvondi® to prevent and treat bleeding episodes and peri-operative bleeding in adults (age 18 and older) diagnosed with von Willebrand disease.
- Veyvondi® was studied in patients, 18 to 64 years of age, in a multi-center, open label, non-randomized study assessing safety, efficacy and pharmacokinetics, with and without rFVIII. It was also studied in patients, 18 years and older, in a prospective, uncontrolled, international, multi-center, open label, non-randomized study assessing control of hemostasis before, during or after surgical procedures, with or without rFVIII. The most common adverse reaction observed was generalized pruritus (itching). The EMA filing is based on data from these two Phase 3 clinical trials shared publicly in December 2015 and December 2016, respectively.
- • On December 8, 2015, the FDA approved Vonvendi®, von Willebrand factor (Recombinant), for use in adults 18 years of age and older who have von Willebrand disease (VWD). Vonvendi® is the first FDA-approved recombinant von Willebrand factor, and is approved for the on-demand (as needed) treatment and control of bleeding episodes in adults diagnosed with VWD. The safety and efficacy of Vonvendi® were evaluated in two clinical trials of 69 adult participants with VWD. These trials demonstrated that Vonvendi® was safe and effective for the on-demand treatment and control of bleeding episodes from a variety of different sites in the body. No safety concerns were identified in the trials. The most common adverse reaction observed was generalized pruritus (itching). In the pivotal study, all participants (100 percent) reported successful treatment of bleeding episodes, with 96.9 percent of treated bleeds (N=192 bleeds in 22 patients) achieving an “excellent” efficacy rating and 3.1 percent achieving a “good” efficacy rating. Most bleeds (81.8 percent) were resolved with a single infusion, and the treatment showed a mean half-life of 21.9 hours (± 8.36). Vonvendi® is expected to be broadly available in the United States in late 2016. Baxalta expects to file for regulatory approvals in Europe in 2017 and in other markets around the world. The FDA granted Vonvendi® orphan product designation for these uses.
- • On December 22, 2014, Baxter International announced that the company has submitted a biologics license application (BLA) to the FDA for the approval of BAX111, the first highly-purified recombinant von Willebrand Factor (rVWF) in clinical development as a treatment for patients with von Willebrand disease. The filing was based on the completion of a Phase III, multi-center, open-label clinical trial assessing the safety, efficacy and pharmacokinetics of BAX111. The study met its primary efficacy endpoint defined by the number of patients who achieved treatment success for control of bleeding episodes. All patients treated in the full analysis set (n=22) experienced a 100% treatment success rating based on a 4-point efficacy rating scale, comparing prospectively estimated number of infusions needed to treat the bleeding episodes to the actual number of infusions administered. The median number of infusions required to treat bleeding events in the trial was 1.0 and the majority of events (81.1%) were resolved with a single infusion. A total of 125 adverse events (AE\'s) following 318 infusions occurred in 25/37 subjects. Eight AEs were considered causally related to BAX111: six non-serious related AEs (tachycardia, infusion site paresthesia, electrocardiography (ECG) T-wave inversion, dysgeusia, generalized pruritis and hot flush) occurred in four patients, and two related SAEs (chest discomfort and increased heart rate) occurred in one patient.
- Baxter expects to publish additional data from the trial in the coming months. Both the European Commission and the FDA have granted orphan-drug designation for BAX111.
Patents:
Submission of marketing authorization application USA : 2014-12-22
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2015-12-08
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2011-11-23
Orphan status UE: 2010-11-26
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
