Canadian children now have access to ADYNOVATE^®, which offers a twice-weekly prophylaxis dosing schedule and on-demand control of bleeding episodes¹

TORONTO, Nov. 26, 2018 /CNW/ - Shire Pharma Canada ULC (Shire Canada), the leading global biotechnology company focused on rare diseases, is pleased to announce that on November 21, 2018 Health Canada authorized the extended indication for ADYNOVATE^® [Antihemophilic Factor (Recombinant), PEGylated] for children under the age of 12 living with hemophilia A.¹ In Canada, hemophilia A affects fewer than 1 in 10,000 people, or about 2,500 individuals.²

With this approval, Canadians under the age of 12 living with hemophilia A will now have access to ADYNOVATE^®, the first extended half-life (EHL) PEGylated (Recombinant) factor VIII treatment available for:¹

• Control and prevention of bleeding episodes
• Prophylaxis to prevent or reduce the frequency of bleeding episodes
• Perioperative management

ADYNOVATE^® is designed to offer twice-weekly prophylaxis dosing as well as on-demand control of bleeding episodes for children with hemophilia A and for use during surgery.¹ It is built on ADVATE^® [Antihemophilic Factor (Recombinant)],¹ the world's most widely used FVIII treatment.

"It is an exciting time in hemophilia care, with many promising products in the pipeline and coming to market," said Paul Wilton, President, Canadian Hemophilia Society.

Health Canada's authorization of the extended indication for ADYNOVATE^® was based on data from a multi-centre, open-label, prospective, uncontrolled Phase 3 clinical study of patients under 12 years of age.¹

The safety and efficacy of ADYNOVATE^® was evaluated in a total of 73 pediatric previously treated patients (PTPs) with severe hemophilia A, of which 66 subjects were dosed (32 subjects aged <6 years and 34 subjects aged 6 to <12 years).¹ The prophylactic regimen was 40 to 60 IU/kg of ADYNOVATE twice a week, with a mean (SD) dose of 51.1 IU/kg (5.5).¹ The ABR was analyzed in a negative binomial model with the presence or absence of target joints and age at screening <6 years versus 6 to <12 years as covariates, and the duration of the observation period in years as an offset.¹ The point estimate for the overall mean ABR was 3.04 (95% CI 2.21 – 4.19), with a median of 2.0.¹ The point estimate for the mean ABR of spontaneous bleeds was 1.16 (95% CI 0.74 – 1.83), with a median of 0, and for joint bleeds it was 1.10 (95% CI 0.64 – 1.91), with a median of 0.¹

Of the 66 subjects treated prophylactically:¹

• 73 per cent experienced no joint bleeding episodes
• 67 per cent experienced no spontaneous bleeding episodes
• 38 per cent experienced no bleeding episodes

ADYNOVATE^® was first approved in Canada in November 2016, for use in hemophilia A patients 12 years and older for on-demand treatment, prophylaxis and perioperative management to reduce the frequency of bleeding episodes.

"As a leader in developing innovative therapies to improve care for hemophilia patients, Shire is pleased to now offer a treatment option that can help Canadians manage hemophilia A from early childhood through to adulthood," said Eric Tse, General Manager, Shire Canada. "ADYNOVATE^®'s unique PEGylation technology allows patients to achieve their treatment goals by providing bleed protection and extending time between treatments, allowing patients to spend more time leading active lives, doing what they love."

About Hemophilia A
Hemophilia A, the most common type of hemophilia, is a rare bleeding disorder that causes longer-than-normal bleeding due to lack of clotting factor VIII in the blood.³ Hemophilia primarily affects males, with an incidence of one in 5,000 male births.⁴ The severity of hemophilia A is determined by the amount of factor in the blood, with more severity associated with lower amounts of factor.⁵ More than half of patients with hemophilia A have the severe form of the condition.⁵ Approximately 25-30% of individuals with severe hemophilia A develop inhibitors.⁶ Inhibitors are a rare, but a serious medical problem that can occur when a person with hemophilia has an immune response to treatment with clotting factor concentrates.⁷

About ADYNOVATE^®
ADYNOVATE^® is built on the full-length ADVATE^® molecule,¹ a treatment for hemophilia A that has been used by patients worldwide for more than 13 years.⁸ ADYNOVATE^® provides proven prophylaxis with twice-weekly dosing for patients with hemophilia A, helping to further individualize options for this patient population.¹ The PEGylation technology was selected because it maintains the integrity of the parent molecule (ADVATE^®) and reduces the time at which the body clears ADYNOVATE^®, resulting in an extended circulating half-life.¹

ADYNOVATE^® is contraindicated in patients who have had prior anaphylactic reaction to ADYNOVATE^®, to the parent molecule (ADVATE^®[Antihemophilic Factor (Recombinant)]), mouse or hamster protein, or excipients of ADYNOVATE^® (e.g. Tris, calcium chloride, mannitol, sodium chloride, trehalose, glutathione, histidine, and/or polysorbate 80).¹

The most common adverse reactions (≥1% of subjects) reported in the clinical studies were headache, diarrhea, nausea and rash.¹

Hypersensitivity reactions have been reported with ADYNOVATE^®.¹ Allergic-type hypersensitivity reactions, including anaphylaxis, are rare complications of treatment with recombinant antihemophilic factor, including the parent molecule, ADVATE^®.¹ Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur.¹

PEG exposure levels resulting from ADYNOVATE^® therapy are very low.¹ Based upon available experimental data, there is also a lack of evidence supporting the potential for accumulation of the specific PEG (20kDA) used in the pegylation of ADYNOVATE^®.¹ The potential for PEG accumulation with ADYNOVATE^® is therefore considered to be low.¹

Formation of neutralizing antibodies (inhibitors) to factor VIII can occur following administration of factor VIII products.¹ Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests.¹ Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled with expected dose.¹ Inhibitor development has been reported in ADYNOVATE^®.¹

The safety and efficacy of ADYNOVATE^® in routine prophylaxis and the treatment of bleeding episodes have been evaluated in 66 previously treated children aged less than 12 years.¹ There were no severe bleeding episodes in the study and none of the subjects underwent surgery.¹

Pharmacokinetic studies in children (<12 years) have demonstrated higher clearance, a shorter half-life and lower incremental recovery of factor VIII compared to adults.¹

To report SUSPECTED ADVERSE REACTIONS, contact Shire at drugsafety@shire.com, or Health Canada at 1-866-234-2345 or https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/adverse-reaction-reporting.html.

Please see full Prescribing Information within the Canadian Product Monograph.

About Shire
Shire is the global biotechnology leader serving patients with rare diseases and specialized conditions. We seek to push boundaries through discovering and delivering new possibilities for patient communities who often have few or no other champions. Relentlessly on the edge of what's next, we are serial innovators with a diverse pipeline, offering fresh thinking and new hope. Serving patients and partnering with healthcare communities in over 100 countries, we strive to be part of the entire patient journey to enable earlier diagnosis, raise standards of care, accelerate access to treatment, and support patients. Our diverse portfolio of therapeutic areas includes Immunology, Hematology, Genetic Diseases, Neuroscience, Internal Medicine and Ophthalmics.

Championing patients is our call to action: it brings the opportunity and responsibility to change people's lives. www.shire.com

About Shire Pharma Canada ULC
Shire Pharma Canada ULC is a subsidiary of Shire. Our Canadian office is located in Toronto, Ontario. For more information, please visit: www.shirecanada.com.