Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.8 (FAST)
 758 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Icatibant [HOE 140, JE 049] is a potent, specific and selective peptidomimetic bradykinin B2-receptor antagonist. It has a modified peptide structure, and is the first bradykinin receptor antagonist to act on the guinea-pig trachea without demonstrating agonist effects. Icatibant was originated by Hoechst Marion Roussel (now sanofi-aventis). Jerini AG is seeking a worldwide partner for the development and marketing of icatibant for the treatment of refractory ascites in liver cirrhosis and seeking a partner in Asia, North America, South America and Australia for angioedema. In August 2004, Aventis merged with Sanofi-Synthelabo to form sanofi-aventis. Icatibant has shown an excellent safety profile in phase I studies. In December 2003, Jerini demonstrated positive results in the phase IIa study. Results obtained were statistically significant and clinically relevant. At the BIO 2004 International Annual Convention (BIO-2004) [San Francisco, CA, USA; 6-9 June 2004], Jerini reported plans to initiate phase IIb trials in this indication in the second half of 2004. It was announced in September 2004 by Jerini that a pivotal registration study, known as FAST 1 (For Angioedema Subcutaneous Treatment), had been initiated in the US and Canada. The protocol of a European study, known as FAST 2, was submitted to the authorities in September 2004. Jerini is currently conducting pivotal/registration trials for angioedema in the US, Canada and Europe. During the 3rd Annual BioPartnering North America Conference (BPN-2005), Jerini announced that it expects to complete registration trials in the second half of 2005/first half of 2006, with a launch of icatibant for HAE in 2007. The US FDA granted fast-track status to icatibant in July 2004 for the treatment of HAE. Effective December 2003, icatibant gained orphan drug status in the US for the same indication. Previously, in January 2003, the European Agency for the Evaluation of Medicinal Products granted icatibant orphan drug status in Europe for the treatment of angioedema.
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PMID:Icatibant: HOE 140, JE 049, JE049. 1599 85

Icatibant is a selective antagonist of the bradykinin type 2 receptor. In the randomized, double-blind, multicentre, FAST-1 trial, the difference in the median time to the onset of symptom relief (primary endpoint) did not reach statistical significance between a single dose of subcutaneous icatibant 30 mg and placebo in adults with moderate to very severe acute abdominal or cutaneous episodes of hereditary angioedema. However, icatibant was effective with regard to several other endpoints, providing significantly greater reductions from baseline in symptom severity scores 4 and 12 hours after administration, and eliciting significantly shorter times to both first symptom improvement and overall patient improvement than placebo. In the similarly designed, active comparator-controlled, FAST-2 trial, a single dose of subcutaneous icatibant 30 mg was associated with a significantly shorter median time to onset of symptom relief (primary endpoint) than oral tranexamic acid in adults with acute abdominal or cutaneous episodes of hereditary angioedema, and was also more effective than tranexamic acid in terms of most other endpoints. Across both FAST-1 and -2, the efficacy of subcutaneous icatibant 30 mg in the treatment of laryngeal episodes of hereditary angioedema was generally consistent with that seen for abdominal and cutaneous episodes, with a median time to first symptom improvement of 0.6-1.0 hours. Subcutaneous icatibant was generally well tolerated in adult patients with hereditary angioedema in the FAST trials, with the most common adverse events being injection-site reactions that were generally of mild severity, transient in nature and resolved spontaneously without treatment.
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PMID:Icatibant. 2003 Apr 26

Bradykinin is the key mediator of symptoms of hereditary angioedema (HAE), a rare genetic disorder characterized by recurrent episodes of edema of the skin, mucosa and muscle. Icatibant, a bradykinin B(2) receptor antagonist, is an effective and generally well-tolerated treatment option for acute attacks of type I and II HAE. A Phase III randomized, double-blind, placebo-controlled study, FAST-3 (NCT00912093), was designed to further evaluate the efficacy and safety of icatibant in patients presenting with moderate to very severe cutaneous and/or abdominal or mild-to-moderate laryngeal symptoms. Severe laryngeal attacks were treated with open-label icatibant. The controlled phase of FAST-3, completed in October 2010 with results published in December 2011, demonstrated that compared with placebo, icatibant evoked clinically meaningful and statistically significant efficacy across multiple end points in the treatment of type I and II HAE attacks. In addition, icatibant was generally well tolerated and no drug-related serious adverse events were experienced.
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PMID:Clinical efficacy of icatibant in the treatment of acute hereditary angioedema during the FAST-3 trial. 2316 82