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Shire receives European approval for label extension of CINRYZE for pediatric HAE

Thursday, March 16, 2017

Shire announced that the European Commission (EC) has approved a label extension granting three new indications for CINRYZE (C1 inhibitor [human]), broadening its use to children with hereditary angiodema (HAE), a rare, genetic disorder that results in recurring attacks of edema (swelling).

The body sites most commonly affected are mainly the extremities and abdomen. CINRYZE is now indicated for routine prevention of angioedema attacks in children (ages 6 years and above) with severe and recurrent attacks of HAE who are intolerant to or insufficiently protected by oral preventions treatments, or patients who are inadequately managed with repeated acute treatment. It is the first and only HAE treatment with this indication in paediatric patients. CINRYZE is also now approved for the treatment and pre-procedure prevention of angioedema attacks in children (ages 2 years and above) with HAE.

Symptoms of HAE often present in childhood, and while attacks can occur at any age, early onset may predict a more severe disease course. Attacks often occur in children without a clear trigger, and may affect a child’s participation in school, activities, and sports, which can leave them feeling socially isolated. Less frequently, HAE can cause life-threatening attacks due to obstruction in the upper airways.

“This pediatric label expansion demonstrates our ongoing commitment to improving the lives of patients of all ages living with HAE,” said Philip J. Vickers, Ph.D., head of R&D, Shire. “We believe the future of HAE means preventing attacks before they happen, and are proud to now be able to offer the first long-term preventative treatment for pediatric patients. As we expand our HAE portfolio, we remain focused on innovative solutions that fulfil unmet needs for people worldwide living with this rare disease.”

CINRYZE has been approved since 2011 for these indications in adults and adolescents ages 12-17 years with HAE.

Henrik Balle Boysen, executive director of HAEi, stated, “Over the years we have encountered many children who suffer from frequent and severe HAE symptoms that often occur spontaneously and without warning. Despite improvements in the management of HAE in recent years, this new long-term prophylaxis indication for alleviating the frequency of HAE symptoms will be a welcome addition for families with HAE in Europe.”

CINRYZE will be available for use in pediatric patients later in 2017 throughout Member States of the European Union (EU), as well the European Economic Area (EEA) in which Shire currently has a license in the adult and adolescent population.

HAE is a rare, genetic disorder that affects an estimated one in 50,000 people worldwide and results in recurring attacks of edema (swelling).

Long-term prophylaxis refers to the routine use of medication to prevent episodes of angioedema, and may be considered for severely symptomatic patients with HAE. Management of HAE also includes on-demand treatment of swelling attacks (known as acute treatment) to minimize the consequences of the symptoms, and pre-procedure prevention, which is often used before certain surgeries and to cover other periods of high risk of attack (such as stressful times including school examinations, for example).

The efficacy of CINRYZE for the treatment and prevention of angioedema attacks in pediatric patients with HAE has been demonstrated in two open-label studies (LEVP 2006-1 and LEVP 2006-4) and two pediatric clinical studies (0624-203 and 0624-301).

Two studies demonstrated the efficacy of CINRYZE for the treatment of HAE in patients ages 6-11 years. The first study (LEVP 2006-1) included 22 pediatric patients (of a total of 101 enrolled patients) who were treated for 121 acute HAE attacks. The proportion of HAE attacks achieving unequivocal relief of the defining symptom within four hours after treatment was comparable between the 22 children (ages 2-17 years) and adults enrolled in the study, with 89% and 86% of attacks achieving relief, respectively.

The second study (0624-203) enrolled nine pediatric patients who received a single dose of CINRYZE based on their weight with children weighing between 10 and 25 kg (n=3) receiving 500 units and those weighing >25 kg receiving either 1000 units (n=3) or 1500 units (n=3). All nine (100%) subjects achieved unequivocal beginning of relief of the defining symptom within four hours following initiation of treatment with CINRYZE. The 1500-unit dose is not an approved dosage.

In addition, two studies demonstrated the efficacy of CINRYZE for the prevention of HAE in pediatric patients. The first study (LEVP 2006-4) included 23 pediatric patients (of a total of 146 enrolled patients) between the ages of 3 and 17 years. The children received 1000 units of CINRYZE every three to seven days, with the exception of a 3-year-old child who received 500 units every three to seven days. Prior to enrolment, the children reported a median of three HAE attacks each month. While receiving CINRYZE prophylaxis during the study, 87% of the children reported an average of one or fewer attack per month, which were comparable to those observed in adults in the study.

The second study (0624-301) included six pediatric subjects ages 6-11 years who were randomized to twice-weekly CINRYZE dosing for 12 weeks in two treatment sequences (500/1000 units or 1000/500 units). Both doses resulted in similar reduction of attack-frequency and showed clinical benefit regarding severity, duration, and requirement for acute treatment of attacks.

For three subjects under the age of 6 years, administration of CINRYZE (500 units or 1000 units) was associated with increases in C1 INH levels and clinical efficacy in acute treatment and prevention of attacks. Overall administration of CINRYZE was well tolerated.

Across clinical studies, there were 61 unique pediatric subjects enrolled and exposed to over 2,500 infusions of CINRYZE (2-5 years, n=3; 6-11 years, n=32; 12-17 years, n=26). Among these children, adverse reactions with CINZYRE included headache, nausea, pyrexia, and infusion site erythema. None of these adverse reactions were severe, and none led to discontinuation of medicinal product. Overall, the safety and tolerability of CINRYZE were similar in children, adolescents, and adults.

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