AZD-9668 (alvelestat) is an oral neutrophil elastase inhibitor being developed as an innovative new therapy for the treatment of alpha-1 antitrypsin deficiency (AATD).

AATD is a genetic disorder that causes a deficiency of alpha-1 antitrypsin. There are approximately 50,000 and 60,000 severe patients in North America and Europe respectively, who are either ZZ or Null.  It can cause pulmonary emphysema, a life-threatening lung disease, resulting in severe shortness of breath and wheeze.  The lung damage in AATD results from the loss of the normally protective effect of alpha-1 antitrypsin against damaging enzymes released during inflammation, specifically neutrophil elastase, that lead to the irreversible destruction of the lungs’ supportive elastic tissues.  The aim is to use AZD-9668 (alvelestat) to inhibit neutrophil elastase activity and prevent further damage to patients’ lungs.

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REFERENCES

  1. Silverman & Sandhaus (2009) Alpha1-Antitrypsin Deficiency. NEJM 360: 2749-2757
  2. Blanco et al (2017) Alpha-1 Antitrypsin Pi*Z Gene Frequency And Pi*ZZ Genotype Numbers Worldwide: An Update. Int J COPD 12: 561-569
  3. Blanco et al (2017) Alpha-1 Antitrypsin Pi*SZ Genotype: Estimated Prevalence And Number Of SZ Subjects Worldwide Int J COPD 12: 1683-1694
  4. Rodriguez-Frias et al (2012) Rare Alpha-1-antitrypsin Variants: Are They Really So Rare? Ther Adv Respir Dis 6: 79-84
  5. NORD – Alpha-1 Antitrypsin Deficiency
  6. Vogelmeier C et al. A Randomised, Placebo-controlled, Dose-finding Study Of AZD9668, An Oral Inhibitor Of Neutrophil Elastase, In Patients With Chronic Obstructive Pulmonary Disease Treated With Tiotropium. COPD. 2012 Apr;9(2):111-120
  7. Stockley R et al. Phase II Study Of A Neutrophil Elastase Inhibitor (AZD9668) In Patients With Bronchiectasis. Respir Med. 2013 Apr;107(4):524-533
  8. Elborn JS et al. Efficacy, Safety And Effect On Biomarkers Of AZD9668 In Cystic Fibrosis. Eur Respir J. 2012 Oct;40(4):969-976
  9. Nordenmark LH et al. Feasibility of Computed Tomography in a Multicenter COPD Trial: A Study of the Effect of AZD9668 on Structural Airway Changes. Adv Ther. 2015 Jun;32(6):548-566

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