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Date: 2018-01-08

Type of information: Granting of a Market Authorisation in the EU

Product name: Adynovate®/Adynovi® (EU) - BAX 855

Compound: rurioctocog alfa pegol

Therapeutic area: Hematological diseases - Genetic diseases - Rare diseases

Action mechanism:

  • blood coagulation factor/protein. Adynovate®/BAX 855  is a full-length FVIII molecule pegylated recombinant factor VIII. BAX 855 is based on Advate® and leverages proprietary PEGylation technology designed to extend the duration of activity of proteins in the body. The drug has been developed through a collaboration with Nektar Therapeutics.

Company: Baxalta (USA - IL) now Shire (UK - USA)

Disease: hemophilia A

Latest news:

  • • On January 8, 2018, the European Commission (EC) has granted Marketing Authorization for Adynovi®, an extended half-life recombinant factor VIII (rFVIII) treatment, for on-demand and prophylactic use in patients 12 years and older living with hemophilia A. The Marketing Authorization is based on outcomes from three Phase 3 clinical trials of patients with hemophilia A. These include a prospective, global, multi-center, open label, non-randomized study of patients 12 to 65 years of age; a prospective, uncontrolled, open label, multi-center study of patients 12 years of age and younger; and a study of perioperative control of hemostasis with interim study results from 15 patients with severe hemophilia A undergoing surgical procedures.
  • • On November 9, 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Adynovi®. This extended half-life recombinant Factor VIII (rFVIII) treatment is intended for the treatment and prophylaxis of bleeding in patients 12 years and above with haemophilia A. Adynovi® will be available as a powder and solvent for solution for injection (250 IU, 500 IU, 1000 IU and 2000 IU). The benefits with Adynovi® are its ability to prevent and control bleeding when used on demand and during surgical procedures, as seen in clinical trials in adult and paediatric patients with haemophilia A. The most common side effects are headache, diarrhoea, nausea and rash. It is proposed that Adynovi be prescribed by physicians experienced in the treatment of haemophilia.
  • The CHMP submission was based on outcomes from three Phase 3 clinical trials of patients with hemophilia A. These include a prospective, global, multi-centre, open label, non-randomized study of patients 12 to 65 years of age; a prospective, uncontrolled, open label, multi-centre study of patients 12 years of age and younger; and a study of perioperative control of hemostasis with interim study results from 15 patients with severe hemophilia A undergoing surgical procedures.
  • • On December 27, 2016, Shire announced that the FDA has approved Adynovate® [Antihemophilic Factor (Recombinant), PEGylated], an extended circulating half-life recombinant Factor VIII (rFVIII) treatment for hemophilia A, in pediatric patients under 12 years of age. The FDA also approved Adynovate® for use in surgical settings for both adult and pediatric patients. Adynovate® is built on the full-length Advate® [Antihemophilic Factor (Recombinant)] molecule, a market leading treatment for hemophilia A with more than 13 years of real-world patient experience.
  • The approval of Adynovate® to treat children under the age of 12 was based on data from a prospective, uncontrolled, open-label, multi-center Phase 3 trial designed to assess the immunogenicity along with the safety and efficacy of Adynovate®. Results from the study showed that Adynovate® met its primary endpoint with no previously treated children having developed inhibitory antibodies to Adynovate®. In addition, no treatment-related serious adverse events were reported. More than 70 percent (73 percent) of children had zero joint bleeds (n=48/66) while on prophylactic treatment with Adynovate® and nearly 40 percent (38 percent) experienced zero bleeds (n= 25/66). The median overall annualized bleeding rate (ABR) among pediatric patients treated with Adynovate® was 2.0 (mean ABR 3.04; range 2.21–4.19), which was similar to the rates seen in the adult study. Approval to use Adynovate® in surgical settings for both adult and pediatric patients was based on interim results of an ongoing Phase 3 study of perioperative control of hemostasis among 15 patients with severe hemophilia A undergoing surgical procedures.
  • Adynovate® was first approved by the FDA in November 2015. Through a collaboration with Nektar Therapeutics, Adynovate® leverages proprietary PEGylation technology designed to extend the amount of FVIII available for use in the body. The technology was selected because it maintains the integrity of the parent molecule (ADVATE) while reducing the time at which the body clears Adynovate®, resulting in an extended circulating half-life.
  • • On March 2, 2016, Baxalta announced that it has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for approval of Adynovi®, an extended circulating half-life recombinant Factor VIII (rFVIII) treatment, for pediatric, adolescent and adult patients with hemophilia A and for use during surgery.
  • Adynovi® was studied in patients, 12 to 65 years of age, in a prospective, global, multi-center, open label, non-randomized study; in patients 12 years of age and younger, in a prospective, uncontrolled, open-label, multi-center study; and for the perioperative control of hemostasis among 15 patients with severe hemophilia A undergoing surgical procedures. The EMA filing is based on data from these three Phase 3 clinical trials, which Baxalta shared publicly in December 2015 .
  • • On February 25, 2016, Baxalta announced that it has submitted supplemental Biologics License Applications (sBLAs) to the FDA seeking approval for the use of Adynovate® to treat children under the age of 12 with hemophilia A and for use in surgical settings. The submission of Adynovate® to treat children under the age of 12 was based on results of a Phase 3 trial designed to assess the efficacy and safety including immunogenicity of Adynovate®, which was initially reported in December 2015 . Results from the study showed Adynovate® met its primary endpoint and no patients developed inhibitory antibodies to Adynovate®. In addition, no treatment-related serious adverse events were reported. More than 70 percent (72.7 percent) of patients had no joint bleeds while on treatment with Adynovate® (n=66) and nearly 40 percent (37.9 percent) experienced zero bleeds. The median overall annualized bleeding rate (ABR) among patient participants treated with Adynovate® was 2.0 (range 0-49.8; mean ABR 3.0), which was comparable to the rates seen in the adult study.
  • The filing was also supported by the positive results of a Phase 3 study evaluating the efficacy and safety of Adynovate® for the perioperative control of hemostasis among 15 patients with severe hemophilia A undergoing surgical procedures, which was reported in December 2015 . The study data demonstrated that Adynovate® achieved hemostasis control in the perioperative period (from start of the procedure until discharge or day 14) for patients with severe hemophilia A. Baxalta continues to invest in Adynovate® to expand the product’s value for more patients worldwide. Baxalta plans to file for marketing authorization in Europe in the first quarter of 2016 and expects regulatory approval of the treatment in Japan in the first half of the year. Adynovate® is also under regulatory review in Canada and Switzerland .
  • • On November 30, 2015, Baxalta announced the launch and first shipments of Adynovate® [Antihemophilic Factor (Recombinant), PEGylated], an extended circulating half-life recombinant factor VIII (rFVIII) treatment for hemophilia A based on full-length ADVATE [Antihemophilic Factor (Recombinant)].
  • • On November 13, 2015,  Baxalta announced that the FDA has approved Adynovate® [Antihemophilic Factor (Recombinant), PEGylated], an extended circulating half-life recombinant Factor VIII (rFVIII) treatment for hemophilia A. In the pivotal phase 3 clinical trial, which served as the foundation for the approval, Adynovate® demonstrated efficacy in treating hemophilia patients through routine prophylaxis as well as for on-demand bleeding episodes. Patients, 12 to 65 years of age, in the prospective, global, multi-center, open label, non-randomized study were assigned to either twice weekly prophylaxis (40-50 IU/kg, n=120) or on-demand treatment (10-60 IU/kg, n=17) with Adynovate®. The study found that previously-treated patients in a twice-weekly prophylaxis arm had 95 percent fewer annual bleeds compared to those treated on-demand [median annual bleed rate (ABR) 1.9 vs. 41.5, respectively]. During the study, 38 percent (n=120) of prophylaxis-treated patients experienced zero bleeds. Moreover, 57 percent of patients experienced zero joint bleeds based on six months of prophylaxis with Adynovate®.
  • Nearly all (98 percent) of patients on prophylaxis with Adynovate® did not have a dose adjustment in the study. Nearly all (96 percent) bleeding episodes (n=591) were controlled with one or two infusions of Adynovate®. No patients developed inhibitors to the treatment; the most common adverse reactions (=1 percent of subjects) were headache and nausea.Adynovate® will be available in the United States in the coming weeks.
  • Currently, studies are ongoing in previously treated patients (PTPs) with severe hemophilia A undergoing surgery and in pediatric PTPs under the age of 12 with severe hemophilia A. Additionally, Baxalta will initiate a study in previously-untreated patients (PUPs) with severe hemophilia A. Baxalta has filed for regulatory approval of the treatment in Japan and following completion of the pediatric study, expects to file for marketing authorization in Europe.
  • • On April 16, 2015, Baxter International  announced that the company has submitted a new drug application (NDA) to Japan's Ministry of Health, Labour and Welfare for the approval of BAX 855, an investigational, extended half-life recombinant factor VIII (rFVIII) treatment based on Advate® [Antihemophilic Factor (Recombinant)] for patients over 12 years of age with hemophilia A. The submission follows the filing to the FDA in late 2014 and is based on positive results from a prospective, global, Phase 3 study of 137 previously treated patients (PTP). The results, presented during the European Association for Haemophilia and Allied Disorders (EAHAD) meeting in February 2015 , demonstrated that BAX 855 met its primary endpoint in the control and prevention of bleeding episodes and routine prophylaxis for patients who were 12 years or older.Patients in a twice-weekly prophylaxis arm experienced a 95 percent reduction in median annual bleed rate (ABR) as compared to those in the on-demand arm (1.9 vs. 41.5, respectively). BAX 855 was also effective in treating bleeding episodes, 96 percent of which were controlled with one or two infusions. No patients developed inhibitors to BAX 855 and no treatment-related serious adverse events, including hypersensitivity, were reported. The most common product-related adverse reaction was headache (3 patients).
  • • On December 1, 2014, Baxter announced that the company has submitted a biologics license application (BLA) to the FDA for the approval of BAX 855, an investigational, extended half-life recombinant factor VIII (rFVIII) treatment for hemophilia A based on Advate® [Antihemophilic Factor (Recombinant)]. The submission is based on positive results from a prospective, global, multi-center, open-label, two-arm Phase 3 study of 137 previously treated patients (PTP). The results demonstrated that BAX 855 met its primary endpoint in the control and prevention of bleeding episodes and routine prophylaxis for patients who were 12 years or older. Patients in a twice-weekly prophylaxis arm experienced a 95 percent reduction in median ABR as compared to those in the on-demand arm (1.9 vs. 41.5, respectively). BAX 855 was also effective in treating bleeding episodes, 96 percent of which were controlled with one or two infusions. No patients developed inhibitors to BAX 855 and no treatment-related serious adverse events, including hypersensitivity, were reported. The most common (three patients) product-related adverse reaction was headache. Upon approval, BAX 855 is expected to be produced at the company's Singapore manufacturing facility, one of several sites currently approved for Advate® production.
 

Patents:

Submission of marketing authorization application USA : 2014-12-01

Submission of marketing authorization application UE: 2016-03-02

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2015-11-13/2016-12-27

UE authorization: 2018-01-08

Favourable opinion UE: 2017-11-09

Favourable opinion USA:

Orphan status USA:

Orphan status UE:

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes