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DOI: 10.1055/s-0029-1238919
A Pipeline of Therapies for Cystic Fibrosis
Publication History
Publication Date:
16 September 2009 (online)
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ABSTRACT
Therapeutics development for cystic fibrosis (CF) involves a coordinated effort among many groups, including individuals with CF and their caregivers, clinical research teams, and those in academia and industry who have discovered and developed the therapeutic strategies. In the United States, the Cystic Fibrosis Foundation (CFF) has devoted over $875 million to facilitate and coordinate this process since 1986, resulting in the clinical development and/or assessment of ~50 drug candidates during that time. The more than 30 compounds currently in the pipeline of Foundation-funded therapeutics are used as a platform to discuss why and how therapeutic strategies are brought into clinical development. Consideration is also given to the funding, management, and infrastructure necessary and practical to support the progression of drug candidates and the availability of therapeutics for use by individuals with CF. The importance of the clinical trial process and relevant outcome measures to assess the efficacy of drug candidates is also discussed. Finally, the potential impact of the pipeline for individuals with CF is summarized.
KEYWORDS
Cystic fibrosis - drug development - clinical trials
REFERENCES
- 1 Flume P A, Robinson K A, O'Sullivan B P Clinical Practice Guidelines for Pulmonary Therapies Committee et al. Cystic fibrosis pulmonary guidelines: airway clearance therapies. Respir Care. 2009; 54 522-537
- 2 Flume P A, O'Sullivan B P, Robinson K A Cystic Fibrosis Foundation, Pulmonary Therapies Committee et al. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2007; 176 957-969
- 3 Stallings V A, Stark L J, Robinson K A, Feranchak A P, Quinton H. Clinical Practice Guidelines on Growth and Nutrition Subcommittee . Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review. J Am Diet Assoc. 2008; 108 832-839
- 4 Cystic Fibrosis Foundation .Patient Registry Annual Data Report to the Center Directors 2007. Annual Report. Bethesda, MD; Cystic Fibrosis Foundation 2008
- 5 Welsh M J, Smith A E. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell. 1993; 73 1251-1254
- 6 MacDonald K D, McKenzie K R, Zeitlin P L. Cystic fibrosis transmembrane regulator protein mutations: “class” opportunity for novel drug innovation. Paediatr Drugs. 2007; 9 1-10
- 7 Accurso F J, Rowe S M, Durie P et al.. Interim results of phase 2A study of VX-770 to evaluate safety, pharmacokinetics, and biomarkers of CFTR activity in cystic fibrosis subjects with G551D [abstract]. Pediatr Pulmonol Suppl. 2008; 31 295
- 8 Shak S, Capon D J, Hellmiss R, Marsters S A, Baker C L. Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum. Proc Natl Acad Sci U S A. 1990; 87 9188-9192
- 9 Konstan M W, Davis P B. Pharmacological approaches for the discovery and development of new anti-inflammatory agents for the treatment of cystic fibrosis. Adv Drug Deliv Rev. 2002; 54 1409-1423
- 10 Konstan M W, Byard P J, Hoppel C L, Davis P B. Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med. 1995; 332 848-854
- 11 Kraynack N C, Chmiel J F, Xue W et al.. Effect of simvastatin on exhaled nitric oxide and inflammatory markers in sputum in patients with cystic fibrosis. Pediatr Pulmonol Suppl. 2008; 31 300
- 12 Konstan M W, Hilliard K A, Bucur C et al.. Effect of pioglitazone on sputum markers of inflammation in cystic fibrosis. Pediatr Pulmonol Suppl. 2008; 31 310
- 13 Williams B, Robinette M, Slovis B, Deretic V, Perkett E. Hydroxychloroquine: pilot study of anti-inflammatory effects in cystic fibrosis. Pediatr Pulmonol Suppl. 2008; 31 314
- 14 Oermann C M, Katz M, Wheeler C, Cumming S. A pilot study evaluating the potential use of low-dose methotrexate as an anti-inflammatory for cystic fibrosis ling disease. Pediatr Pulmonol Suppl. 2007; 30 292-293
- 15 Tirouvanziam R, Conrad C K, Bottiglieri T, Herzenberg L A, Moss R B, Herzenberg L A. High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis. Proc Natl Acad Sci U S A. 2006; 103 4628-4633
- 16 Saiman L, Marshall B C, Mayer-Hamblett N Macrolide Study Group et al. Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2003; 290 1749-1756
- 17 Papas K A, Sontag M K, Pardee C et al.. A pilot study on the safety and efficacy of a novel antioxidant rich formulation in patients with cystic fibrosis. J Cyst Fibros. 2008; 7 60-67
- 18 DiMasi J A, Hansen R W, Grabowski H G. The price of innovation: new estimates of drug development costs. J Health Econ. 2003; 22 151-185
- 19 Dimasi J A. Risks in new drug development: approval success rates for investigational drugs. Clin Pharmacol Ther. 2001; 69 297-307
- 20 Russ A P, Lampel S. The druggable genome: an update. Drug Discov Today. 2005; 10 1607-1610
- 21 Ramsey B W, Boat T F. Outcome measures for clinical trials in cystic fibrosis. Summary of a Cystic Fibrosis Foundation consensus conference. J Pediatr. 1994; 124 177-192
- 22 Katz R. Biomarkers and surrogate markers: an FDA perspective. NeuroRx. 2004; 1 189-195
- 23 Fleming T R. Surrogate endpoints and FDA's accelerated approval process. Health Aff (Millwood). 2005; 24 67-78
- 24 Mayer-Hamblett N, Ramsey B W, Kronmal R A. Advancing outcome measures for the new era of drug development in cystic fibrosis. Proc Am Thorac Soc. 2007; 4 370-377
- 25 De Gruttola V G, Clax P, DeMets D L et al.. Considerations in the evaluation of surrogate endpoints in clinical trials. summary of a National Institutes of Health workshop. Control Clin Trials. 2001; 22 485-502
Melissa A AshlockM.D.
Cystic Fibrosis Foundation Therapeutics, Inc.
6931 Arlington Rd., Ste. 200, Bethesda, MD 20814
Email: mashlock@cff.org