INHALED TREPROSTINIL IN PULMONARY HYPERTENSION DUE TO INTERSTITIAL LUNG DISEASE (PH-ILD)
THE INCREASE STUDY
Peter Smith, PharmD Senior Director Product Development, United Therapeutics Corporation
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SAFE HARBOR STATEMENT
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.
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 www.unither.com.
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WHO Classification of Pulmonary Hypertension 1-3
WHO GROUP 3 PH
PULMONARY HYPERTENSION (PH)
GROUP 1Pulmonary Arterial
Hypertension (PAH)
GROUP 2PH Due to
Left Heart Disease
GROUP 3PH Due to
Lung Disease
GROUP 4PH Due to Chronic
Thromboembolism
GROUP 5PH Due to
Unclear Multifactorial Mechanisms
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INTERSTITIAL LUNG DISEASE (ILD)1-3
Chronic Obstructive Pulmonary Disease (COPD)
Interstitial Lung Disease (ILD)
GROUP 3PH Due to Lung Disease
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Idiopathic Interstitial Pneumonias
NSIP COP
RB-ILD AIP
IPF DIP LIP
PPF
UIP
GROUP 3PH Due to Lung Disease
Pneumoconiosis CPFEChronic Hypersensitivity
Pneumonitis
Pulmonary Eosinophilia
Pulmonary Histiocytosis
Pulmonary Histiocytosis
Environmental and Occupational Diseases Multisystem Diseases Other: Rare Lung Diseases &
Emphysema-Related Diseases
Connective Tissue Disease
Occupational Lung Disease
Sarcoidosis Tuberose Sclerosis
Wegener’s Granulomatosis
INTERSTITIAL LUNG DISEASE (ILD)1-3
Chronic Obstructive Pulmonary Disease (COPD)
Interstitial Lung Disease (ILD)
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SCOPE OF THE PROBLEM4
Patients in US ~230,000
PREVALENCE OF ILD
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SCOPE OF THE PROBLEM4
PREVALENCE OF PH-ILD
Patients in US ~230,000
Patients in US ~30,000
PREVALENCE OF ILD
Variable reports of PH in ILD prevalence
15%
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NO APPROVED THERAPIES FOR WHO GROUP 3 5-13
BOSENTAN / TRACLEER MACITENTAN / OPSUMIT
AMBRISENTAN/ LETAIRIS RIOCIGUAT / ADEMPAS
SILDENAFIL / REVATIO
STEP-IPF study did not achieve 20% change in 6MWD, but did suggest increased quality of life and decreased shortness of breath
BUILD-1,-2,-3: Failed to improve 6MWD and the time to occurrence of lung fibrosis worseningB-PHIT: No improvement in hemodynam-ics, functional class, or symptoms
MUSIC study found no significant differ-ence in PFTs, time to disease worsening, or death
ARTEMIS-IPF was stopped early due to increased rate of disease progression and respiratory hospitalizations. Use Contrain-dicated
RISE-IIP study terminated due to risk of death and other serious adverse events as compared to placebo. Use Contraindicated in Europe
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INCREASE STUDY
WHY INCREASE?
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THE iTRE STUDY RESULTS11
Data are from a retrospective analysis and should be interpreted with the appropriate caution.
p = 0.041
WHO-FUNCTIONAL CLASS I & II 22
41%
Follow-up
18%
Baseline
IV
IIIIII
IVIIII
I+I+
VS
p = 0.022
6-MIN WALK DISTANCE (6MWD) 11
Baseline
243 ± 106 m
+65 m308 ± 109m
Follow-up
Distance0
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VENTILATION (V)/PERFUSION (Q) MISMATCH WITH SYSTEMIC VASODILATORS14-16
INHALED THERAPIES MAY PRESERVE V/Q AND PREVENT UNDESIRABLE EFFECTS ON PERFUSION
Ventilation (V) / Perfusion (Q) Gradient
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INCREASE STUDY DESIGN OVERVIEW
16 WEEKdouble blind study
N=314WHO Group 3 PH associated with ILD including CPFE
RANDOMIZE 1:1
~115 STUDY SITES IN US
NCT02630316
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UTHR Science Day 2018 / INCREASE Study / Peter Smith
INCREASE STUDY DESIGN OVERVIEW
INHALED TREPROSTINIL
PLACEBO
16 WEEKdouble blind study
N=314WHO Group 3 PH associated with ILD including CPFE
RANDOMIZE 1:1
~115 STUDY SITES IN US
NCT02630316
PRIMARY ENDPOINT
6MWD at peak exposure
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UTHR Science Day 2018 / INCREASE Study / Peter Smith
INCREASE STUDY DESIGN OVERVIEW
INHALED TREPROSTINIL
PLACEBO
NCT02630316 16 WEEKdouble blind study
2 YEARSNCT02633293 Open LabelExtension
N=314WHO Group 3 PH associated with ILD including CPFE
RANDOMIZE 1:1
~115 STUDY SITES IN US
PRIMARY ENDPOINT
6MWD at peak exposure
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REFERENCES
AIP: Acute interstitial pneumonitis; COP: Cryptogenic organizing pneumonia; CPFE: Combined pulmonary fibrosis and emphysemaDIP: 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;
1. Simonneau G, et al. J Am Coll Cardiol. 2013;62(25):D34-41.2. Bourke SJ. Postgrad Med J. 2006;82:494-499.3. “Interstitial Lung Disease” www.erswhitebook.com – accessed December 2015.4. United Therapeutics internal market research.5. The Idiopathic Pulmonary Fibrosis Clinical Research Network, et al. N Engl J Med.
2010;363(7):620-628.6. King TE Jr, et al. Am J Respir Crit Care Med. 2008;177(1):75-81.7. Seibold JR, et al. Arthritis Rheum. 2010;62(7):2101-2108.8. King TE Jr, et al. Am J Respir Crit Care Med. 2011;184(1):92-99.9. Corte TJ, et al. Am J Respir Crit Care Med. 2014;190(2):208-217.
10. Raghu G, et al. Eur Respir J. 2013;42(6):1622-1632.11. Faria-Urbina, M., Oliveira, R.K.F., Agarwal, M., Waxman A.B., et al. Lung (2018) 196:139.
https://doi.org/10.1007/s00408-017-0081-7.12. Raghu et al. Ann Inter Med. 2013; 158(9):641-9.13. Nathan et al. Eur Resp Journal. 2017, 50 (suppl 61). DOI: 10.1183/1393003.congress-2017.
OA198514. Rubin LJ. New Engl J Med. 1997;336(2):111-117.15. Rubin LJ. Chest. 1993;104:236-250.16. Seeger W, et al. J Am Coll Cardiol. 2013;62(25 Suppl):D109-116.
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