New Models of Care in Idiopathic Pulmonary Fibrosis Implementing New Pharmacologic Therapies

History of Pharmacotherapy for IPF 2012 PANTHER trial results released Prednisone, azathioprine and N-acetylcysteine combination therapy associated with an increased risk for death and hospitalization when used for IPF October 2014 2 agents receive FDA approval for the treatment of mild-to-moderate IPF Pirfenidone Nintedanib Raghu G, et al, 2012; King TE, et al, 2014; Richeldi L, et al, 2014

Pirfenidone: Benefits Efficacy ASCEND trial showed a reduced decrease in FVC compared to placebo at 52 weeks Early disease No apparent difference in efficacy in early vs advanced disease, arguing for early treatment Progressive disease ASCEND post-hoc analysis trial showed a significant reduction in further decline of FVC in patients who continued on pirfenidone after an initial decline of ≥10% in FVC Mortality Trend toward a mortality benefit at 52 weeks in the combined CAPACITY trials and the ASCEND trial King TE, et al, 2014.

Pirfenidone: AE Profile* Adverse Event % Patients Nausea 37.6 Dyspnea 30.9 Progression of IPF 29.3 Diarrhea 28.1 Rash 25.0 Dizziness 21.2 Dyspepsia 18.4 Vomiting 15.9 Weight loss 15.6 * Taken from pooled data from 5 clinical trials (ie, Compassionate-use trial, CAPACITY I and II, ASCEND + extension) of pirfenidone in IPF in a total of 1299 patients. Cotton & Mayer, 2015; Collard HR, et al, 2015.

Nintedanib: Benefits Efficacy Early disease Progressive disease Demonstrated in INPULSIS I and II phase 3 trials 150 mg bid dose produced a significant slowing in reduction in FVC Early disease Similar efficacy in treatment subgroups, independent of disease severity and type of IPF on diagnosis Progressive disease Results from the TOMORROW extension trial suggest that benefits in slowing disease progression may be maintained to week 76 Mortality Trend toward a mortality benefit at 52 weeks in pooled INPULSIS trials Richeldi L, et al, 2014; Richeldi L, et al, 2015.

Nintedanib: AE Profile* *Results From the TOMORROW Trial and Extension Adverse Event % Patients Diarrhea 64.7 Nausea 23.5 Vomiting 16.5 Decreased appetite 15.3 Cough 12.9 Nasopharyngitis Bronchitis Earache Headache Upper Abdominal Pain IPF Progression 10.6 Upper Respiratory Tract Infection Fatigue Dyspnea 9.4 Back Pain 8.2 Richeldi L, et al, 2011.

Current Standards of Management of IPF Consider therapy with an antifibrotic agent. Manage cough. Promote exercise and pulmonary rehabilitation. Recommend appropriate vaccinations. Infections are poorly tolerated in these patients. Manage comorbidities. Clinical trial considerations Lung transplant consideration

Common Comorbidities in IPF Pulmonary Extra-Pulmonary Emphysema Coronary artery disease Pulmonary hypertension Heart failure Lung cancer Gastroesophageal reflux disease Venous thromboembolism Obstructive sleep apnea Depression

Treatment Strategies for Comorbidities in IPF Accurate diagnosis Disease-targeted therapy Pulmonary rehabilitation and oxygen therapy Evaluation for lung transplant

2015 IPF Guideline Updates: Treatment 2011 guidelines did not recommend any therapy for IPF Published before the approval pharmacologic therapies specific to IPF. “2015 Update to Guidelines for the Treatment of Idiopathic Pulmonary Fibrosis” includes 2 new FDA-approved therapies Pirfenidone - conditional recommendation based on a moderate confidence in estimate of effects Nintedanib - conditional recommendation based on a moderate confidence in estimate of effects Unknown in both agents: Therapeutic benefits of patients excluded from trials Optimal duration of therapy Long-term effects Updated guidelines to be published in the American Journal of Respiratory and Critical Care Medicine in August 2015. Raghu G. ATS 2015; May 2015; Denver, CO.