Phase III study showed Ofev® slows the loss of pulmonary function in people living with systemic sclerosis associated ILD

Ridgefield, Conn., May 20, 2019 – Boehringer Ingelheim today announced that the SENSCIS® trial met its primary endpoint: reduction in the annual rate of decline in forced vital capacity (FVC) in patients with systemic sclerosis associated interstitial lung disease (SSc-ILD). Results showed that Ofev® (nintedanib) slows the loss of pulmonary function by 44% in patients with SSc-ILD relative to placebo, as measured by FVC over 52 weeks. These new data were published today in the New England Journal of Medicine (NEJM) and presented to the medical community at the American Thoracic Society (ATS) International Conference in Dallas.

SENSCIS is the largest randomized controlled trial to be conducted in patients with SSc-ILD, a disease for which there are currently no approved treatments. Results demonstrated that nintedanib was generally well-tolerated with the most common side effect being diarrhea. The safety and tolerability profile in SSc-ILD patients was similar to that previously observed in idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib.

“These study results are welcome news for doctors and their patients because lung fibrosis, which results in shortness of breath and persistent coughing, is a devastating and often fatal consequence of systemic sclerosis,” said study investigator Kristin Highland, M.D., pulmonologist with the Cleveland Clinic.

Results from this study form the basis of the application for regulatory approval of nintedanib in SSc-ILD that was filed with the FDA and EMA by Boehringer Ingelheim in the first quarter of 2019. The FDA recently granted priority review to the supplemental application for nintedanib in SSc-ILD. The regulatory submissions 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, marketed as Ofev, is already approved in more than 70 countries for the treatment of IPF.

“The study provides positive evidence that nintedanib significantly slows the progression of lung function decline for those living with systemic sclerosis who are diagnosed with interstitial lung disease,” said Thomas Leonard, Ph.D., executive director, Clinical Development and Medical Affairs, Specialty Care, Boehringer Ingelheim. “Boehringer Ingelheim is pleased that the FDA has recognized the urgency to bring a new treatment to patients by designating the application as a priority review.”

About the results
SENSCIS, a Phase III double-blind, randomized, 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. 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, similar to the results from the Phase III INPULSIS® trials in IPF. FVC is an established measurement of lung function. As ILD progresses, lung function gradually and irreversibly deteriorates.

There was no difference between groups for secondary endpoints, skin thickness and quality of life, as measured at week 52 by the modified Rodnan Skin Score (mRSS) and the St. George’s Respiratory Questionnaire (SGRQ), respectively.

In the study, the percentage of total adverse events were similar in both groups. A higher incidence of diarrhea, the most common side effect, was reported in the nintedanib group (75.7%) versus the placebo group (31.6%).

About systemic sclerosis
Systemic sclerosis, also known as scleroderma, is a rare disease characterized by thickening and scarring of connective tissue throughout the body. It is estimated that up to 2.5 million people worldwide have systemic sclerosis, including approximately 100,000 people in the United States. The disease can cause scarring of the skin, lungs (interstitial lung disease), heart and kidneys, which can be debilitating and may become life-threatening. Approximately 25 percent of patients develop significant pulmonary involvement within three years of diagnosis. Lung involvement is the leading cause of death among people with systemic sclerosis.

What is Ofev?
Ofev is a prescription medicine used to treat people with a lung disease called idiopathic pulmonary fibrosis (IPF). It is not known if Ofev is safe and effective in children.

Important Safety Information

What is the most important information I should know about Ofev (nintedanib)?

Ofev can cause harm, birth defects or death to an unborn baby. Women should not become pregnant while taking Ofev. Women who are able to become pregnant should have a pregnancy test before starting treatment and should use birth control during and for at least 3 months after your last dose. If you become pregnant while taking Ofev, tell your doctor right away.

What should I tell my doctor before using Ofev?

Before you take Ofev, tell your doctor if you have:

• liver problems
• heart problems
• a history of blood clots
• a bleeding problem or a family history of a bleeding problem
• had recent surgery in your stomach (abdominal) area
• any other medical conditions.

Tell your doctor if you:

• are pregnant or plan to become pregnant.
• are breastfeeding or plan to breastfeed. It is not known if Ofev passes into your breast milk. You should not breastfeed while taking Ofev.
• are a smoker. You should stop smoking prior to taking Ofev and avoid smoking during treatment.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, herbal supplements such as St. John’s wort.

What are the possible side effects of Ofev?

Ofev may cause serious side effects.

TELL YOUR DOCTOR RIGHT AWAY if you are experiencing any side effects, including:

• Liver problems. Unexplained symptoms may include yellowing of your skin or the white part of your eyes (jaundice), dark or brown (tea colored) urine, pain on the upper right side of your stomach area (abdomen), bleeding or bruising more easily than normal, feeling tired, or loss of appetite. Your doctor will do blood tests regularly to check how well your liver is working during your treatment with Ofev.
• Diarrhea, nausea, and vomiting. Your doctor may recommend that you drink fluids or take medicine to treat these side effects. Tell your doctor if you have these symptoms, if they do not go away, or get worse and if you are taking over-the-counter laxatives, stool softeners, and other medicines or dietary supplements.
• Heart attack. Symptoms of a heart problem may include chest pain or pressure, pain in your arms, back, neck or jaw, or shortness of breath.
• Stroke. Symptoms of a stroke may include numbness or weakness on 1 side of your body, trouble talking, headache, or dizziness.
• Bleeding problems. Ofev may increase your chances of having bleeding problems. Tell your doctor if you have unusual bleeding, bruising, or wounds that do not heal and/or if you are taking a blood thinner, including prescription blood thinners and over-the-counter aspirin.
• Tear in your stomach or intestinal wall (perforation). Ofev may increase your chances of having a tear in your stomach or intestinal wall. Tell your doctor if you have pain or swelling in your stomach area.

The most common side effects of Ofev are diarrhea, nausea, stomach pain, vomiting, liver problems, decreased appetite, headache, weight loss, and high blood pressure.

These are not all the possible side effects of Ofev. For more information, ask your doctor or pharmacist. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/safety/medwatch or call 1-800-FDA-1088.

For full prescribing information, including patient information, please visit www.Ofev.com.

About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, Conn., is the largest U.S. subsidiary of Boehringer Ingelheim Corporation.

Boehringer Ingelheim is one of the world’s top 20 pharmaceutical companies. Headquartered in Ingelheim, Germany, the company operates globally with approximately 50,000 employees. Since its founding in 1885, the company has remained family-owned, and today our goal is to improve the lives of humans and animals through its three business areas: human pharmaceuticals, animal health and biopharmaceutical contract manufacturing.

Boehringer Ingelheim concentrates on developing innovative therapies that can improve and extend patients’ lives. As a research-driven pharmaceutical company, it plans in generations for long-term success. Its research efforts are focused on diseases with high, unmet medical need. In animal health, the company stands for advanced prevention.

In 2018, Boehringer Ingelheim achieved net sales of around $20.7 billion (17.5 billion euros). R&D expenditure of almost $3.7 billion (3.2 billion euros) corresponded to 18.1 per cent of net sales.

Boehringer Ingelheim is committed to improving lives and strengthening our communities. Please visit www.boehringer-ingelheim.us/csr to learn more about Corporate Social Responsibility initiatives.

For more information please visit www.boehringer-ingelheim.us, or follow us on Twitter @BoehringerUS.

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