INS1009—INHALED TREPROSTINIL PRODRUG
INS1009 is an investigational, sustained-release, inhaled treprostinil prodrug in development for Pulmonary Arterial Hypertension (PAH). INS1009 has the potential to address some of the current limitations of existing inhaled prostanoid therapies such as dosing frequency and a decreased amount of drug administered, which may lead to greater tolerability.
PAH is a serious, progressive rare disease which ultimately leads to heart failure.1-3 PAH has a 15% one-year mortality rate.4 In studies of patient databases, the estimated PAH prevalence rate in Europe is 15-52 cases per million Europe.5 In a study of a privately insured and a Medicare claims database, the estimated PAH prevalence rate in the US is 109 cases per million among the privately insured (age<65) population and 451 cases per million among the Medicare (age≥65) population.6
INS1009: An Investigational Inhaled Prostanoid Treatment for PAH
Insmed has applied its unique drug design expertise to develop an inhalation suspension of the product hexadecyl-treprostinil, contained within approximately 100 nanometer particles. Once deposited in the lung, lung esterases convert the prodrug into the active drug treprostinil, as shown through in vitro and in vivo animal studies.7
INS1009: A Unique Inhaled Prostanoid Treatment
The goal is to develop a treatment that enables 24-hour dosing. If achieved, it may offer patients a more convenient dosing regimen over current inhaled products which must be dosed four times or more per day.8,9
This pro-drug suspension formulation was designed to optimize treprostinil’s retention within the nanoparticles and will be investigated as a once daily nebulization.
1Humbert M, Sitbon O, Chaouat A, et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med. 2006;173(9):1023-1030.
2Yang X, Mardekian J, Sanders KN, Mychaskiw MA, Thomas JI. III Prevalence of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review of the literature. Clin Rheumatol. 2013;32(10):1519-1531.
3Kane GC, Maradit-Kremers H, Slusser JP, Scott CG, Frantz RP, McGoon MD. Integration of clinical and hemodynamic parameters in the prediction of long-term survival in patients with pulmonary arterial hypertension. CHEST. 2011;139(6):1285- 1293.
4Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long-term survival from time to diagnosis in pulmonary arterial hypertension from the REVEAL registry. CHEST. 2012;142(2):448-456.
5Peacock AJ, Murphy NF, McMurray JJV, Caballero L, Stewart S. An epidemiological study of pulmonary arterial hypertension. Eur Respir J. 2007;30(1):104-109.
6Kirson, KY, Birnbaum HG, Ivanova JI, et al. Prevalence of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in the United States. Curr Med Res Opin. 2011;27(9):1763-1768.
7Leifer F, Omiatek D, Malinin V, et al. Prolonged activity of inhaled treprostinil prodrug nanoparticles in a rat model of pulmonary arterial hypertension. Poster presented at: European Respiratory Society (ERS) International Congress. September 6-10, 2014; Munich, Germany. Poster 2356.
8Tyvaso [package insert]. Research Triangle Park, NC: United Therapeutics Corp; 2014.
9Ventavis [package insert]. South San Francisco, CA: Actelion Pharmaceuticals US, Inc; 2013.