Type of information: Granting of a Market Authorisation in Japan
Product name: Firazyr®
Compound: icatibant - synthetic decapeptide
Therapeutic area: Rare diseases - Genetic diseases
- peptide. Icatibant is a specific bradykinin B2 receptor antagonist designed to block the effects of bradykinin, the key mediator of edema formation
Company: Shire (UK)
Disease: acute attacks of hereditary angioedema (HAE) in adult and paediatric patients
- • On September 21, 2018, Shire announced that the Ministry of Health, Labour and Welfare (MHLW) in Japan has granted manufacturing and marketing authorisation for Firazyr® (icatibant injection), for the acute treatment of hereditary angioedema (HAE) attacks in adult patients with HAE. The use of Firazyr® in Japanese patients was examined in an open-label, single-arm, Phase 3 study of 8 adult patients with a confirmed diagnosis of HAE who experienced angioedema attacks. During the study, 3 patients self-administered Firazyr® and 5 patients had Firazyr® administered by a physician. The primary efficacy endpoint was time to onset of symptom relief (TOSR), defined as a 50% reduction from baseline in patient Visual Analog Scale (VAS) score. The study showed that Firazyr® was well tolerated and demonstrated symptom relief during an acute HAE attack through a single injection. Overall, median TOSR was 1.75 hours, and TOSR was similar for patients who self-administered Firazyr® or who had Firazyr® administered by a physician. Symptom relief was attained as early as 1 hour after Firazyr® injection and all patients had symptom relief within 5 hours. The most common adverse events in patients treated with Firazyr® were injection site reactions such as erythema, or swelling, which were found to be mild to moderate in severity.
- • On October 26, 2017, Shire announced that the European Commission (EC) has approved a label extension granting a new indication for Firazyr® (icatibant injection), broadening its use to adolescents and children aged 2 years and older, with hereditary angioedema (HAE) caused by C1-esterase-inhibitor (C1-INH) deficiency. Firazyr® has been approved in the European Union (EU) since 2008 for symptomatic treatment of acute attacks of HAE in adults with C1-INH deficiency. The use of Firazyr® in paediatric patients was studied in an open label, non-randomised single-arm study, involving 32 paediatric patients with HAE. The efficacy population consisted of 11 children and 11 adolescents with attacks. The primary efficacy endpoint was time to onset of symptom relief (TOSR) based on the investigator-assessed composite post-treatment symptom score, defined as earliest time post-treatment when 20% or more improvement in the composite symptom score was achieved, without worsening of any single component score. Overall, median TOSR was 1.0 hour, with no differences between children and adolescents. More than 70% of patients experienced symptom relief at 1.1 hours, and more than 90% by 2 hours post-treatment.
- The majority of paediatric patients who were treated with subcutaneous Firazyr® experienced injection site reactions such as erythema, swelling, burning sensation, skin pain and itching/pruritus; these were found to be mild to moderate in severity and consistent with reactions that have been reported in adults. The study showed Firazyr® was well tolerated and demonstrated rapid resolution of symptoms during an HAE attack through a single injection. The study that led to this approval is the first and only trial investigating a subcutaneous therapy in the HAE paediatric population. Firazyr® will be available for use in paediatric patients in Europe beginning in Q4.
- • On September 14, 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for Firazyr®. The drug is now indicated for symptomatic treatment of acute attacks of hereditary angioedema (HAE) in adults, adolescents and children aged 2 years and older, (with C1-esterase-inhibitor deficiency).
- • On June 23, 2011, Shire has announced that the Pulmonary-Allergy Drugs Advisory Committee to the FDA recommended, by a vote of twelve to one, that the efficacy and safety data provides substantial evidence to support approval of Firazyr® (icatibant) for the treatment of acute attacks of hereditary angioedema (HAE) in patients 18 years and older. In addition, by a vote of eleven to one, with one abstention, the Committee recommended self-administration of the drug by patients.
- • On March 3, 2011, Shire announced that the European Commission has approved Firazyr® (icatibant) for self-administration after training in subcutaneous injection technique by a healthcare professional. Firazyr® is the first and only treatment for acute Type I and Type II hereditary angioedema (HAE) attacks licensed for self-administration in Europe. The European Commission approval of the Firazyr® label change to include self-administration is valid in all of the 27 EU Member States plus Iceland, Liechtenstein and Norway. Firazyr® is currently approved in 37 countries worldwide, including the countries of the European Union.
- • On February 28, 2011, Shire announced it has submitted a complete response to the not approvable letter issued by the FDA to Jerini in April 2008 regarding its New Drug Application for Firazyr® (icatibant) for the treatment of acute attacks of hereditary angioedema (HAE). Shire\'s complete response includes additional data requested by the agency regarding Firazyr®\'s efficacy and safety in treating HAE attacks. Shire conducted an additional Phase III clinical study (FAST-3), and in December 2010 reported positive efficacy and safety results. The Company's complete response is based primarily on recent results from the FAST-3 study and the ongoing self-administration study, as well as the previously published FAST-1 and FAST-2 studies.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2011-08-25
UE authorization: 2008-07-15/2017-10-26
Favourable opinion UE:
Favourable opinion USA: 2011-06-23
Orphan status USA: 2003-11-25
Orphan status UE: 2003-02-17
Pediatric exclusivit _USA:
Pediatric exclusivity UE: