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38702711000001108

New Medicines

Adynovi (EU); Adynovate (US) Haemophilia A - treatment and prophylaxis of bleeding in patients 12 years and above

Information

Adynovi (EU); Adynovate (US)
New formulation
Shire
Shire

Development and Regulatory status

Launched
Launched
Launched
July 2020
Jan 22MHRA approve new 3000iu strength version of Adynovi with same indication as existing Adynovi products [19].
Jul 20Available in UK. List prices: 250iu, 1=£212.50; 500iu, 1=£425; 1000iu, 1=£850; 2000iu, 1=£1700 [18].
Mar 20Adynovi is not yet available in the UK. Takeda has submitted a tender bid to NHS England for rurioctocog, and awaits the results summer 2020 [17].
Jan 19No update on plans for UK launch are available [16].
Mar 18Rurioctocog alfa pegol was launched in the US in Nov 15 [15].
Jan 18Approved in EU
Nov 17EU positive opinion for treatment and prophylaxis of bleeding in patients 12 years and above with haemophilia A (congenital factor VIII deficiency) [13].
Mar 16Filed in EU [12].
Dec 15Baxalta plan to file for marketing authorisation in Europe and aims to file for a paediatric indication in the US in early 2016 [11].
Nov 15Approved in US for treatment and prevention of bleeding episodes in adults and adolescents with Haemophilia A [10].
Jul 15Remains PIII for use during surgery, PK guided, in paediatrics and continuation use [9].
Dec 14Baxter submitted a biologics license application for US FDA approval Of BAX 855, extended half-life recombinant FVIII for Hemophilia A - the application is based on the ADVATE study (n=138) [4].
Dec 14Baxter plans to file in Europe in 2016 after an on-going paediatric study is complete [5].
Aug 14Baxter plans to file in the US by end 2014 and later, after completion of the paediatric study, in the EU [3].
Nov 13Company expects to file for approval late in 2014 [2]

Category

Full-length recombinant factor VIII conjugated to polyethylene glycol
Haemophilia A is caused by factor VIII deficiency and occurs in 1 in 5,000 to 1 in 10,000 male live births. Between 50% and 70% of people with haemophilia A have severe disease (<1% factor VIII activity). There were 5,424 patients with haemophilia A in the UK in 2011 (prevalence 8.7 per 100,000 population), 1,057 were aged 0-13 years.
Haemophilia A - treatment and prophylaxis of bleeding in patients 12 years and above
Intravenous

Trial or other data

Dec 15ADYNOVATE meets endpoints in PIII trial (n=73) of Haemophilia A in pts under 12 yrs of age. The prospective, uncontrolled, open-label, multi-centre PIII study was designed to assess the safety and immunogenicity of ADYNOVATE. Previously-treated patients aged <12 with severe haemophilia A received prophylactic ADYNOVATE treatment (median 1.9 infusions per week) and were followed for six months. The treatment´s haemostatic efficacy in prophylaxis and treatment of bleeding was assessed. ADYNOVATE met its primary endpoint as no pts developed inhibitory antibodies to ADYNOVATE. No treatment-related serious adverse events were reported. 72.7 % of pts had no joint bleeds and 37.9% experienced no bleeds. The median annualized bleeding rate (ABR) among pts treated with ADYNOVATE was 2.0 (range 0-49.8; mean ABR 3.0), which was comparable to rates seen in the adult study [11].
Jul 15Results of BAX 855 trials published in blood journal [8].
Jul 15Baxalta announces positive data. Patients in the twice-weekly arm of the trial demonstrated a 95% reduction in median annualised bleed rate compared with the on-demand arm (1.9 vs. 41.5, respectively). BAX 855 was also effective in treating all bleeding episodes, 95.9% of which were controlled with one or two infusions at a median dose of 29.0 IU/kg per infusion [7].
Aug 14In top-line results from a global 6 month PIII study (n=138) BAX 855 met its primary endpoint in the control and prevention of bleeding, routine prophylaxis and perioperative management for patients ≥ 12 years. Patients on twice-weekly prophylaxis arm had a 95% reduction in median annualized bleed rates (ABR) vs those in the on-demand arm (1.9 vs. 41.5, respectively). BAX 855 was also effective in treating bleeding episodes, 96% of which were controlled with one or two infusions. The half-life of BAX 855 was 1.4 - 1.5 times that of ADVATE. No patients developed inhibitors to BAX 855 and no treatment-related serious AEs, including hypersensitivity, were reported [3].
Nov 13NCT01736475 (PROLONG-ATE) is a PII/III, multi-center, open label study of efficacy, safety, and pharmacokinetics of PEGylated recombinant Factor VIII (BAX 855) administered for prophylaxis and treatment of bleeding in 146 previously treated patients (aged 12-65 years) with severe Haemophilia A. Patients will receive treatment twice weekly (45 IU/kg) and followed for 6 months. The primary outcome is annualized bleeding rate. The study started Jun 13 and is due to complete Sep 14. Baxter is also initiating a continuation study (NCT01945593) [1].
Nov 13NCT01913405 is a PIII, multi-centre, open label study of efficacy and safety of PEGylated rFVIII (BAX 855) in 30 previously treated patients with severe Haemophilia A undergoing surgical or other invasive procedures. The primary outcome is Global Hemostatic Efficacy Assessment score (GHEA). the pre-operative loading dose and any intra-operative and post-operative dosing will be based on individual PK results as well as target trough level for type of surgery. The study started Sep 13 and is due to complete Dec 16 [1]

Evidence based evaluations