INHALED TREPROSTINIL IN PULMONARY HYPERTENSION DUE TO INTERSTITIAL LUNG DISEASE (PH-ILD)

Transcription

1 THE INCREASE STUDY INHALED TREPROSTINIL IN PULMONARY HYPERTENSION DUE TO INTERSTITIAL LUNG DISEASE (PH-ILD) Peter Smith, PharmD Senior Director Product Development, United Therapeutics Corporation

2 2 SAFE HARBOR STATEMENT Remarks today concerning United Therapeutics may include forward-looking statements which represent United Therapeutics expectations or beliefs regarding future events. We caution that such statements involve risks and uncertainties that may cause actual results to differ materially from those in the forward-looking statements. Consequently, all such forward-looking statements are qualified by the cautionary language and risk factors set forth in United Therapeutics periodic and other reports filed with the SEC. There can be no assurance that the actual results, events or developments referenced in such forward-looking statements will occur or be realized. United Therapeutics assumes no obligation to update these forward-looking statements to reflect actual results, changes in assumptions or changes in factors affecting such forward-looking statements. This presentation and any related discussions or statements are intended to educate investors about our company. Sometimes that process includes reporting on the progress and results of clinical trials or other developments with respect to our products. This presentation and any related discussions or statements are not intended to promote our products, to suggest that our products are safe and effective for any use other than what is consistent with their FDA-approved labeling, or to provide all available information regarding the products, their risks, or related clinical trial results. Anyone seeking information regarding the use of one of our products should consult the full prescribing information for the product available on our website at Adempas is a registered trademark of Bayer HealthCare Pharmaceuticals. Letairis is a registered trademark of Gilead Sciences, Inc. Opsumit is a trademark of Actelion Pharmaceuticals Ltd. Revatio is a registered trademark of Pfizer Inc. Tracleer is a registered trademark of Actelion Pharmaceuticals Ltd. Tyvaso is a registered trademark of United Therapeutics Corporation.

3 3 WHO GROUP 3 PH WHO Classification of Pulmonary Hypertension 1-3 PULMONARY HYPERTENSION (PH) GROUP 1 Pulmonary Arterial Hypertension (PAH) GROUP 2 PH Due to Left Heart Disease GROUP 3 PH Due to Lung Disease GROUP 4 PH Due to Chronic Thromboembolism GROUP 5 PH Due to Unclear Multifactorial Mechanisms

4 4 INTERSTITIAL LUNG DISEASE (ILD) 1-3 GROUP 3 PH Due to Lung Disease Interstitial Lung Disease (ILD) Chronic Obstructive Pulmonary Disease (COPD)

5 5 INTERSTITIAL LUNG DISEASE (ILD) 1-3 GROUP 3 PH Due to Lung Disease Interstitial Lung Disease (ILD) Chronic Obstructive Pulmonary Disease (COPD) Idiopathic Interstitial Pneumonias Environmental and Occupational Diseases Multisystem Diseases Other: Rare Lung Diseases & Emphysema-Related Diseases IPF DIP LIP NSIP COP PPF RB-ILD AIP UIP Pneumoconiosis Chronic Hypersensitivity Pneumonitis Connective Tissue Disease Sarcoidosis Wegener s Granulomatosis Occupational Lung Disease Tuberose Sclerosis CPFE Pulmonary Histiocytosis Pulmonary Eosinophilia Pulmonary Histiocytosis

6 6 SCOPE OF THE PROBLEM 4 PREVALENCE OF ILD Patients in US ~230,000

7 7 SCOPE OF THE PROBLEM 4 PREVALENCE OF ILD PREVALENCE OF PH-ILD 15% Variable reports of PH in ILD prevalence Patients in US ~230,000 Patients in US ~30,000

8 8 NO APPROVED THERAPIES FOR WHO GROUP SILDENAFIL / REVATIO STEP-IPF study did not achieve 20% change in 6MWD, but did suggest increased quality of life and decreased shortness of breath BOSENTAN / TRACLEER BUILD-1,-2,-3: Failed to improve 6MWD and the time to occurrence of lung fibrosis worsening B-PHIT: No improvement in hemodynamics, functional class, or symptoms MACITENTAN / OPSUMIT MUSIC study found no significant difference in PFTs, time to disease worsening, or death AMBRISENTAN/ LETAIRIS ARTEMIS-IPF was stopped early due to increased rate of disease progression and respiratory hospitalizations. Use Contraindicated RIOCIGUAT / ADEMPAS RISE-IIP study terminated due to risk of death and other serious adverse events as compared to placebo. Use Contraindicated in Europe

9 9 INCREASE STUDY WHY INCREASE?

10 10 THE itre STUDY RESULTS 11 6-MIN WALK DISTANCE (6MWD) 11 p = WHO-FUNCTIONAL CLASS I & II 22 p = Baseline Follow-up 0 Distance 243 ± 106 m +65 m 308 ± 109m IV I+ II 18% III Baseline VS III IV 41% Follow-up I+ II Data are from a retrospective analysis and should be interpreted with the appropriate caution.

11 11 VENTILATION (V)/PERFUSION (Q) MISMATCH WITH SYSTEMIC VASODILATORS Ventilation (V) / Perfusion (Q) Gradient INHALED THERAPIES MAY PRESERVE V/Q AND PREVENT UNDESIRABLE EFFECTS ON PERFUSION

12 12 INCREASE STUDY DESIGN OVERVIEW NCT WEEK double blind study N=314 WHO Group 3 PH associated with ILD including CPFE RANDOMIZE 1:1 ~115 STUDY SITES IN US

13 13 INCREASE STUDY DESIGN OVERVIEW INHALED TREPROSTINIL NCT WEEK double blind study N=314 WHO Group 3 PH associated with ILD including CPFE PRIMARY ENDPOINT RANDOMIZE 1:1 6MWD at peak exposure ~115 STUDY SITES IN US PLACEBO

14 14 INCREASE STUDY DESIGN OVERVIEW INHALED TREPROSTINIL NCT WEEK double blind study N=314 WHO Group 3 PH associated with ILD including CPFE PRIMARY ENDPOINT RANDOMIZE 1:1 6MWD at peak exposure NCT Open Label Extension 2 YEARS ~115 STUDY SITES IN US PLACEBO

15 15 REFERENCES 1. Simonneau G, et al. J Am Coll Cardiol. 2013;62(25):D Bourke SJ. Postgrad Med J. 2006;82: Interstitial Lung Disease accessed December United Therapeutics internal market research. 5. The Idiopathic Pulmonary Fibrosis Clinical Research Network, et al. N Engl J Med. 2010;363(7): King TE Jr, et al. Am J Respir Crit Care Med. 2008;177(1): Seibold JR, et al. Arthritis Rheum. 2010;62(7): King TE Jr, et al. Am J Respir Crit Care Med. 2011;184(1): Corte TJ, et al. Am J Respir Crit Care Med. 2014;190(2): Raghu G, et al. Eur Respir J. 2013;42(6): Faria-Urbina, M., Oliveira, R.K.F., Agarwal, M., Waxman A.B., et al. Lung (2018) 196: Raghu et al. Ann Inter Med. 2013; 158(9): Nathan et al. Eur Resp Journal. 2017, 50 (suppl 61). DOI: / congress OA Rubin LJ. New Engl J Med. 1997;336(2): Rubin LJ. Chest. 1993;104: Seeger W, et al. J Am Coll Cardiol. 2013;62(25 Suppl):D AIP: Acute interstitial pneumonitis; COP: Cryptogenic organizing pneumonia; CPFE: Combined pulmonary fibrosis and emphysema DIP: Desquamative interstitial pneumonia; IPF: Idiopathic Pulmonary Fibrosis; LIP: Lymphoid interstitial pneumonia; NSIP: Nonspecific interstitial pneumonia; PPF: Pleuroparenchymal fibroelastosis; RB-ILD: Respiratory bronchiolitis-associated interstitial lung disease; UIP: Unclassifiable interstitial pneumonia;

16 THANK YOU