Ecallantide

Compound Name:EcallantideMolecular Target:Plasma kallikreinMolecular Structure:Recombinant (60 amino acid) variant of human aprotinin, selected from a phage display libraryLicensed Indication:Acute attacks of hereditary angioedema affecting any body part in patients 16 years of age and olderManufacturer and/or Distributor:Dyax CorporationInitial FDA Approval2009SummaryEcallantide (Kalbitor) is a 60 amino-acid recombinant protein synthesized in the Pichia pastoris strain of yeast. It binds specifically to plasma kallikrein, inhibiting its activity. As a result, kallikrein is unable to cleave high-molecular-weight kininogen to release bradykinin, one of the key effector molecules leading to symptoms in hereditary angioedema. Ecallantide is administered subcutaneously. It must be administered in a healthcare setting due to an anaphylaxis rate of 3.9% of treated patients.̈ In 2009, ecallantide was approved by the FDA for the treatment of acute attacks of hereditary angioedema in patients 16 years of age and older. It has been shown to be effective in improving symptoms of an acute attack within 4 hours of administration and decreasing the need for additional medical intervention 24 hours after administration. More recently, ecallantide has also been shown to be effective in ACE inhibitor-induced angioedema. In 2014, the FDA approved an expansion of the indication of ecallantide to include patients 12 years of age and older. Plasma-derived C1INH, recombinant C1INH, and ecallantide are the only agents license for the treatment of pediatric patients. Ecallantide is also effective in the prevention of blood loss from cardiothoracic surgery. In addition to anaphylaxis, adverse reactions to ecallantide include headache, nausea, fatigue, diarrhea, upper respiratory tract infection, injection site reactions, nasopharyngitis, vomiting, pruritus, abdominal pain, and pyrexia.References

Package Insert: http://www.kalbitor.com/hcp/rems/pdf/KalbitorFullPrescribingInformation.pdf

1. Cicardi M, Levy RJ, McNeil DL, Li HH, Sheffer AL, Campion M, et al. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):523-531. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20818887

2. Levy RJ, Lumry WR, McNeil DL, Li HH, Campion M, Horn PT, et al. EDEMA4: a phase 3, double-blind study of subcutaneous ecallantide treatment for acute attacks of hereditary angioedema. Ann Allergy Asthma Immunol. 2010 Jun;104(6):523-529. 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20568386

3. Schneider L, Lumry W, Vegh A, Williams AH, Schmalbach T. Critical role of kallikrein in hereditary angioedema pathogenesis: a clinical trial of ecallantide, a novel kallikrein inhibitor. J Allergy Clin Immunol. 2007 Aug;120(2):416-422. 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17559913

4. Zuraw B, Yasothan U, Kirkpatrick P. Ecallantide. Nat Rev Drug Discov. 2010 Mar;9(3):189-190. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20190785

5. Sheffer AL, Campion M, Levy RJ, Li HH, Horn PT, Pullman WE. Ecallantide (DX-88) for acute hereditary angioedema attacks: integrated analysis of 2 double-blind, phase 3 studies. J Allergy Clin Immunol. 2011 Jul;128(1):153-159 e154. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21481442

6. Lewis LM, Graffeo C, Crosley P, Klausner HK, Clark CL, Frank A, et al. Ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial. Ann Emerg Med. 2014 Aug 30. pii: S0196-0644(14)00621-0. http://www.ncbi.nlm.nih.gov/pubmed/25182544

7. Stahl MC, Harris CK, Matto S, Bernstein JA. Idiopathic nonhistaminergic angioedema successfully treated with ecallantide, icatibant, and C1 esterase inhibitor replacement. J Allergy Clin Immunol Pract. J Allergy Clin Immunol Pract. 2014 Nov-Dec;2(6):818-9.
 http://www.ncbi.nlm.nih.gov/25439384

8. Culley CM, DiBridge JN, Wilson GL Jr. Off-Label Use of Agents for Management of Serious or Life- threatening Angiotensin Converting Enzyme Inhibitor-Induced Angioedema. Ann Pharmacother. 2016 Jan;50(1):47-59.
 http://www.ncbi.nlm.nih.gov/pubmed/26416949

9. Zanichelli A, Wu MA, Andreoli A, Mansi M, Cicardi M. The safety of treatments for angioedema with hereditary C1 inhibitor deficiency. Expert Opin Drug Saf. 2015 Nov;14(11):1725-36. http://www.ncbi.nlm.nih.gov/pubmed/26429506

10. Lehmann A (August 2008). "Ecallantide (DX-88), a plasma kallikrein inhibitor for the treatment of hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic surgery". Expert Opin Biol Ther. 8 (8): 1187–99. doi:10.1517/14712598.8.8.1187. PMID 18613770.

11. Allergy. 2017 Feb;72(2):300-313. doi: 10.1111/all.13001. Epub 2016 Sep 8. International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency. Farkas H1, Martinez-Saguer I2, Bork K3, Bowen T4, Craig T5, Frank M6, Germenis AE7, Grumach AS8, Luczay A9, Varga L1, Zanichelli A10; HAWK.

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