Past Three Decades Saw An Increasing2

Global Incidence

Deaths

DALY

Due to ILD

What is Interstitial Lung Disease?

Interstitial lung disease (ILD) is an umbrella term used for a large group of diseases that cause scarring (fibrosis) of the lungs.3




Common types of ILD includes:4

Hypersensitivity Pneumonitis

Connective Tissue–Associated ILD

Idiopathic Pulmonary Fibrosis

Idiopathic Nonspecific Interstitial Pneumonia

Sarcoidosis

Pneumoconiosis

Managing ILD5

Lack of recognition of disease at an early stage leads to delayed diagnosis in most patients.

Early diagnosis and prompt appropriate treatment lead to better outcomes for patients with ILD.

Introducing A Comprehensive ILD portfolio

In Idiopathic Pulmonary Fibrosis


Potent inhibitor of TGF-B16


Atternuation of Profibrotic Pathways

Reduced Production of Cytokines and Inflammatory Cell

Rigorously Analyzed In phase 3 Trials6

In 1247 patients with IPF in randomized, double-blind, placebo-controlled, multicenter trials

193ml More FVC vs Placedo at 52 weeks

193ml More FVC vs Placedo at 52 weeks

41% Risk Reduction in lung Function Decline vs Placedo at 52 weeks

41% Risk Reduction in lung Function Decline vs Placedo at 52 weeks

Safe and Tolerable For Long-Term treatment

Safe and Tolerable For Long-Term treatment



Benefits6

Slows Disease Progression & Preserves Lung Function
Reduced the rate of decline in FVC
Reduced deterioration of exercide capacity and dyspnoea
Reduced the risk of all-cause mortality


Dosage

Dosage Titration for patients with IPF

Treatment Days Dosage
Days 0 through 14 1 tab of 200 mg three times daily (600 mg/day)
CDays 15 through 28 2 tab of 200 mf three times daily (1200 mg/day)
Days 29 through 42 1 tab of 600 mg three times daily (1800 mg/day)
Days 43 onwards 1 tab of 200 & 600 mg each three times daily (2400 mg/ day)

Flexible dosing with dose modification may help manage potential GI events and photosensitivity reactions.

Recommended Dosage

150mg Capsule BD

Time Gap Between Two Dosages 12 hours

Maximum Daily Recommended Dosage of 300mg

key findings

SENCIS Trial9

A double randomized trial that evaluted safety and efficacy of Nintedancy 150 mg BD in 576 patients with SSc-ILD



4 out of every 10 patients had stable or improved lung function at 52 weeks with Ninedanib

Inbuild Trial10

Phase-3, randomised, double-blind, placebo-controlled, parallel-group trial on 663 patients with chronic PF-ILDs

Nintedanib Showed significant reduction in annual rate of decline in FVC compared with placebo

As an adjuvant to maintenance therapy in Non-IPD ILD



Shield against Flare-ups

Recommended in International Guidelines for IPF Exacerbation Management11

Offers Survival Benefit

Improves Lung Function

Reduces Lung Inflammation

"The majority of pateients with acute exacerbation of IPF should be treated with corticosteroids"

"ATS/ERS Guidelines for IPF Management"

Anti-Inflammatory and Immune-Suppressive Power to Fight Exacerbations12


A Reassurance for improved Survival in ILD Exacerbations12

Maintenance Dose (take together) 0.5-1.0 mg/kg Methylprednisolone

After intial treatment with CsA and Methylprednisolone Pulsed Therapy


Improved mean Survival rated in AE-ILD Patients

A Safe Immunosuppressant


Mycophenolate mofetil (MMF) use is associated with either stable or improved pulmonary physiology13

In a large diverse cohort of CTD-ILD patients over a medican 2.5 years follow-up13

MMF significantly improved FVC% and DLCO% in two other subgroups, viz. with and without UIP-pattern inujury13

Greater FVC stability
Better Safety profile
Improved overall survival rate

Proven Safety & Toxicity Profile Compared to other Immunosuppressants



Adverse Events MMF Azathioprine Cyclophosphamide
Chronic HP16 30 events 45 events Not studied
Systemic Sclerosis17
Leukopenia 6% Not studied 41%
Neutropenia 4% Not studied 7%
Thrombocytopenia 0% Not studied 6%
Anaemia 1 tab of 200 & 600 mg each three times daily (2400 mg/ day) Not studied 18%

Better proven tolerability compared to Azathioprine and Cyclophosmide18

References

1. Singh S, Bairwa M, Collins BF, et.al, Survival predictors of interstitial lung disease in India: Follow-up of Interstitial Lung Disease India registry. Lung India: Jan–Feb 2021 doi: 10.4103/lungindia.lungindia_414_20 2. Ma X, Zhu L, Kurche JS, et al Global and regional burden of interstitial lung disease and pulmonary sarcoidosis from 1990 to 2019: results from the Global Burden of Disease study 2019Thorax 2022;77:596-605. 3. https://www.lung.org/lung-health-diseases/lung-disease-lookup/interstitial-lung-disease#:~:text=Interstitial%20lung%20disease%20(ILD)%20is,and%20gets%20worse%20over%20time. 4. Singh S, Collins BF, Sharma BS Interstitial Lung Disease in India. Results of a Prospective Registry. American Journal of Respiratory and Critical Care Medicine. 2017. https://doi.org/10.1164/rccm.201607-1484OC 5. Oldham, J. M., & Noth, I. (2014). Idiopathic pulmonary fibrosis: early detection and referral. Respiratory medicine, 108(6), 819–829. https://doi.org/10.1016/j.rmed.2014.03.008 6. King, Talmadge E Jr et al. “A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis.” The New England journal of medicine vol. 370,22 (2014): 2083-92. doi:10.1056/NEJMoa1402582 7. Richeldi L, Cottin V, du Bois RM, et al. Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS(®) trials. Respir Med. 2016;113:74-79. doi:10.1016/j.rmed.2016.02.001 8. Wollin, Lutz et al. “Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis.” The Journal of pharmacology and experimental therapeutics vol. 349,2 (2014): 209-20. doi:10.1124/jpet.113.208223 9. Vasarmidi, E., Tsitoura, E., Spandidos, D. A., Tzanakis, N., & Antoniou, K. M. (2020). Pulmonary fibrosis in the aftermath of the COVID-19 era (Review). Experimental and therapeutic medicine, 20(3), 2557–2560. https://doi.org/10.3892/etm.2020.8980 10. Flaherty KR, Wells AU, Cottin V, Devaraj A, Walsh SLF, Inoue Y, et al., Nintedanib in Progressive Fibrosing Interstitial Lung Diseases, N Engl J Med. 2019 Oct 31;381(18):1718-1727 11. . G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011; 183: 788–824 12. Juarez MM, Chan AL, Norris AG, Morrissey BM, Albertson TE. Acute exacerbation of idiopathic pulmonary fibrosis-a review of current and novel pharmacotherapies. J Thorac Dis. 2015 Mar;7(3):499-519 13. Cassone, G., Sebastiani, M., Vacchi, C., Erre, G., Salvarani, C. and Manfredi, A., 2021. Ecacy and safety of mycophenolate mofetil in the treatment of rheumatic disease-related interstitial lung disease: a narrative review.Drugs in Context, 10, pp.1-17 14. Fischer, A., Brown, K., Du Bois, R., Frankel, S., Cosgrove, G., Fernandez-Perez, E., Huie, T., Krishnamoorthy, M., Meehan, R., Olson, A., Solomon, J. and Swigris, J., 2013. 15. .Brown, K., Rajan, S., Shenoy, P., Mehta, M., Lopez, M., Hegde, R. and Gogtay, J., 2021. The emerging role of mycophenolate mofetil in interstitial lung diseases.Expert Review of Respiratory Medicine, 15(12), pp.1539-1549. 16. .Adegunsoye, A., Oldham, J., Fernández Pérez, E., et al., 2017. Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis.ERJ Open Research, 3(3), pp.00016-2017 17. Tashkin, D., Roth, M., Clements, P., Furst, D., et al., 2016. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial.The Lancet Respiratory Medicine, 4(9), pp.708-719. 18. Brown, K., Rajan, S., Shenoy, P., Mehta, M., Lopez, M., Hegde, R. and Gogtay, J., 2021. The emerging role of mycophenolate mofetil in interstitial lung diseases.Expert Review of Respiratory Medicine, 15(12), pp.1539-1549