New data presented at the American Thoracic Society Conference showed nintedanib slows loss of pulmonary function in people living with systemic sclerosis associated ILD*

Burlington, Ontario, May 27, 2019 – Results from a pivotal Phase III SENSCIS® trial met its primary endpoint: reduction in the annual rate of decline in forced vital capacity (FVC¹) in patients with systemic sclerosis associated interstitial lung disease (SSc-ILD). Interstitial lung disease (ILD) is a key driver of mortality in people living with systemic sclerosis (SSc) – also known as scleroderma – and the absence of treatment options constitutes a high unmet need.^{2, 3}

Results show that nintedanib slows the loss of pulmonary function in patients with SSc-ILD compared to placebo. Patients taking nintedanib showed a 44% reduction in the rate of decline of their lung function, measured in FVC assessed over 52 weeks.¹ These new data were published in the New England Journal of Medicine (NEJM) and presented simultaneously to the medical community at the American Thoracic Society (ATS) International Conference on May 20^th in Dallas.

“There are currently no approved treatments for SSc-ILD, but the SENSCIS data represents a tipping point,” said Dr. Martin Kolb, Director, Division of Respirology, Department of Medicine at McMaster University. “A 44% reduction in lung function decline indicates nintedanib could be life-changing for Canadians living with SSc-ILD, which could significantly improve quality of life.”

SENSCIS® is the largest randomised controlled trial to be conducted in patients with SSc-ILD.^{1, 2, 3} Results also showed that nintedanib had a safety and tolerability profile similar to that observed in patients with idiopathic pulmonary fibrosis (IPF), with the most common adverse event being diarrhea.¹ Nintedanib is already approved in more than 70 countries for the treatment of IPF. 

Systemic sclerosis, also known as scleroderma, is a rare incurable autoimmune disease affecting connective tissue.^{3, 4, 5, 6} It can cause scarring (fibrosis) of the skin as well as major organs such as the heart, lungs, digestive tract and kidneys and can have life-threatening complications.^{2, 3} Approximately 25 per cent of patients develop significant pulmonary involvement within three years of diagnosis.⁷ When SSc affects the lungs it can cause interstitial lung disease (ILD), known as SSc-ILD.^{2, 3} It is a key driver of mortality among people with SSc, accounting for approximately one third of deaths.⁸

SENSCIS®, a Phase III double-blind, randomised, placebo-controlled trial, involved 576 patients across more than 32 countries. The primary endpoint was the annual rate of decline in FVC in mL over 52 weeks.¹ At the end of the 52-week trial, patients receiving nintedanib had an adjusted annual rate of decline in FVC (mL/year) of -52.4 with nintedanib, versus -93.3 with placebo (absolute difference 41.0mL/year [95% CI 2.9, 79.0]; p=0.04). This corresponds to a relative difference of 44% reduction in lung function decline,¹ similar to the results from the Phase III INPULSIS® trials in IPF.⁹ FVC is an established measurement of lung function. As ILD progresses, lung function may gradually and irreversibly deteriorate.¹⁰

“The positive results from the pivotal SENSCIS trial are so encouraging for patients with SSc-ILD,” said Uli Brödl, MD, Vice President Medical and Regulatory Affairs, Boehringer Ingelheim (Canada) Ltd. “Fibrotic lung diseases, including SSc-ILD, are diseases with high unmet needs given the poor prognosis and lack of treatments available. We are committed to researching and developing new therapies for patients suffering from fibrotic lung diseases.”

The SENSCIS® Trial
SENSCIS® was the largest randomised controlled trial to be conducted in patients with SSc-ILD, involving 576 patients across more than 32 countries including Canada, the United States, China, Japan, Germany, France and the United Kingdom. The primary endpoint was the annual rate of decline in lung function as measured in FVC (mL/year) assessed over 52 weeks.¹ The trial also collected data on other manifestations of the disease with key secondary endpoints identified as skin thickness as measured by absolute changes from baseline in modified Rodnan skin score (mRSS) and health-related quality of life measured by the total score on the St George’s Respiratory Questionnaire (SGRQ) at week 52.¹ Enrolment criteria included a diagnosis of SSc with onset of first non-Raynaud symptoms within 7 years, ILD confirmed by high resolution computed tomographic that showed fibrosis affecting at least 10% of the lungs, at least 40% predicted FVC, and a diffusion capacity of the lung for carbon monoxide (DLco) as 30–89% predicted.¹ Patients were randomised to receive nintedanib 150 mg twice daily or placebo. Patients on stable therapy with mycophenolate or methotrexate and/or taking prednisone up to 10 mg/day were allowed to participate.¹

These trial results formed the basis of the application for market authorization of nintedanib in SSc-ILD that was filed with the FDA, EMA and Health Canada by Boehringer Ingelheim in the first quarter of 2019.

Both the FDA and Health Canada recently granted priority review designation for the supplemental application for nintedanib in SSc-ILD. The regulatory applications are part of the company’s ongoing commitment to improving the lives of people living with pulmonary fibrosis, in particular those affected by rare diseases with a high level of unmet need.

Nintedanib 
Nintedanib is already approved in more than 70 countries for the treatment of patients living with idiopathic pulmonary fibrosis (IPF) – a chronic and ultimately fatal disease characterised by a decline in lung function. Over 70,000 people with IPF have been treated with nintedanib.

About systemic sclerosis 
Systemic sclerosis is a rare disease with an estimated 44 of 100,000 Canadians affected.⁶ Because scleroderma affects the connective tissue, symptoms can occur in any area of the body including the skin, muscles, blood vessels and internal organs, making it difficult to diagnose.^{3, 4, 11} In Canada, the disease impacts almost six times as many women as men, and the peak age of onset typically occurs between 40 and 50 years.⁶

Boehringer Ingelheim (Canada) Ltd. 
Improving the health of humans and animals is the goal of Boehringer Ingelheim, a research-driven pharmaceutical company. In doing so, the focus is on diseases for which no satisfactory treatment option exists to date. The company therefore concentrates on developing innovative therapies that can extend patients’ lives. In animal health, Boehringer Ingelheim stands for advanced prevention. 

Family-owned since it was established in 1885, Boehringer Ingelheim is one of the top 20 companies in the pharmaceutical industry. Some 50,000 employees create value through innovation daily for the three business areas of human pharmaceuticals, animal health and biopharmaceuticals. In 2018, Boehringer Ingelheim achieved net sales of around 17.5 billion euros. R&D expenditure of almost 3.2 billion euros, corresponded to 18.1 per cent of net sales. 

As a family-owned company, Boehringer Ingelheim plans in generations and focuses on long-term success. The company therefore aims at organic growth from its own resources with simultaneous openness to partnerships and strategic alliances in research. In everything it does, Boehringer Ingelheim naturally adopts responsibility towards mankind and the environment. 

The Canadian headquarters of Boehringer Ingelheim was established in 1972 in Montreal, Quebec and is now located in Burlington, Ontario. Boehringer Ingelheim employs approximately 600 people across Canada.

More information about Boehringer Ingelheim can be found at www.boehringer-ingelheim.ca or in our annual report: http://annualreport.boehringer-ingelheim.com.

* FVC is Forced Vital Capacity, an established measure of lung function

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References

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3. Denton CP, Khanna D. Systemic sclerosis. www.thelancet.com Published online April 13, 2017 http://dx.doi.org/10.1016/S0140-6736(17)30933-9. Last accessed March 2019.
4. Cottin V, et al. Interstitial lung disease associated with systemic sclerosis (SSc-ILD). Respir. Res. 2019; 20(1): 13.
5. Kowal-Bielecka O, et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017; 76(8): 1327–39.
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9. OFEV® Summary of Product Characteristics-October 2018. Boehringer Ingelheim International GmbH.
10. Ley B, et al. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183: 431–440.
11. Scleroderma Foundation. What is scleroderma? Available at: http://www.scleroderma.org/site/PageNavigator/patients_whatis.html#.V%20hgSaPlVik. Last accessed March 2019.