Efficacy and safety of Ofev® (nintedanib) reinforced in new presentations at ATS 2018

Ridgefield, Conn., May 21, 2018 – Boehringer Ingelheim Pharmaceuticals, Inc. today announced new presentations at the American Thoracic Society’s 2018 annual conference that reinforce the efficacy, safety and tolerability profile of Ofev® (nintedanib) in patients with idiopathic pulmonary fibrosis (IPF).

“The data presented at the conference support the established efficacy of Ofev, while also reaffirming the safety profile observed in the clinical trials and following approval,” said Christopher Corsico, M.D., Chief Medical Officer, Boehringer Ingelheim.

New IPF mortality analysis
Pooled data from the two Phase III INPULSIS® trials and the Phase II TOMORROW study compared the observed number of deaths in patients treated with Ofev or placebo with the predicted rate of death based on GAP stage over one year. GAP stage is used to predict IPF prognosis and is based on gender, age and lung function (as measured by forced vital capacity [FVC] decline predicted and DLco % predicted). Higher stages of GAP are associated with an increasing risk of death.

Across the population (n=1,228), there were fewer deaths observed in each treatment group than predicted based on GAP stage at baseline (Ofev: 42 vs. 89.9; placebo: 41 vs. 64.2). In the Ofev group, the number of observed deaths was 46.7% of the number predicted based on GAP stage, while in the placebo group the number of observed deaths was 63.9% of the number predicted. Based on these differences, the analysis suggests that Ofev may be associated with a 26.8% relative reduction in the risk of death compared with placebo over one year.

“IPF is a progressive and fatal disease, and treatment with nintedanib can slow disease progression by reducing the rate of lung function decline,” said Christopher J. Ryerson, M.D., Assistant Professor at the University of British Columbia Centre for Heart Lung Innovation, Vancouver, Canada. “Although the individual trials were not powered to measure mortality, our pooled analysis suggests that nintedanib may offer a survival benefit for IPF patients.”

Lung function decline and quality of life
In a separate analysis of data from the INPULSIS trials, a greater decline in lung function was associated with worsening patient-reported health-related quality of life (HRQL) measuring respiratory function, shortness of breath, cough and sputum assessment and other quality of life measures. Pooled data from patients treated with Ofev or placebo showed that patients with a decline in FVC >10% predicted, regardless of treatment, experienced declines across different HRQL.

“The symptoms of IPF can have a serious impact on a patient’s quality of life, resulting in a loss of independence and involvement in daily activities,” said Michael Kreuter, M.D., Professor at the Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Care Medicine, University of Heidelberg, and a Member of the German Center for Lung Research, Germany. “Our analysis observed association between the extent of lung function decline and quality of life. Stabilizing lung function, therefore, may allow patients to retain some of their daily level of functioning, which might improve quality of life.”

Pooled safety data from six trials
Data from the largest set of Ofev-treated patients with IPF analyzed to-date further confirmed its safety and tolerability profile. The analysis included patients from six clinical trials (n=1,126), including TOMORROW, the two INPULSIS trials, and their open-label extension studies.

The average exposure to Ofev was 27.7 months with a maximum exposure of 93.1 months, for a total of nearly 2,600 patient-years. The rate of adverse events leading to permanent dose reduction (from 150 mg twice daily to 100 mg twice daily) or discontinuation from the studies were 12.8 and 23.8 events per 100 patient exposure-years, respectively. Diarrhea remained the most common AE, and led to dose reduction or discontinuation in 17.2% and 8.8% of patients, respectively. In the pooled data, the rate of diarrhea was lower than observed in the Phase III INPULSIS trials.

The corresponding abstracts can be found within the ATS online program, here: http://www.abstractsonline.com/pp8/#!/4499

About idiopathic pulmonary fibrosis (IPF)
IPF is a rare and serious lung disease that causes permanent scarring of the lungs. It affects as many as 132,000 Americans, typically men over the age of 65. Early diagnosis and proper care are critical to helping people treat their condition.

About the INPULSIS® trials
INPULSIS®-1 and -2 are two global Phase III trials which evaluated the efficacy and safety of nintedanib in the treatment of idiopathic pulmonary fibrosis (IPF). The INPULSIS® trials were identical in design, e.g., with matching dosing, inclusion criteria and endpoints. INPULSIS® recruited a range of patient types – similar to those seen in clinical practice including patients with early disease (FVC > 90% pred), no honeycombing on HRCT and/or concomitant emphysema. Patients who completed the 52-week treatment period and a 4-week follow-up period in the INPULSIS® trials were offered open-label treatment with Ofev as part of an extension trial to assess the long-term safety and tolerability of Ofev.

About the TOMORROW trial
The Phase II TOMORROW trial was a 12-month, randomised, double-blind, placebo-controlled trial conducted at 92 sites in 25 countries. The trial evaluated the safety and efficacy of oral Ofev at four dosage levels in 432 patients diagnosed with IPF, consistent with the criteria published by the American Thoracic Society (ATS) and European Respiratory Society (ERS). The primary endpoint for the TOMORROW trial was annual rate of decline in forced vital capacity (FVC).

About Ofev® (nintedanib)
The U.S. Food and Drug Administration (FDA) approved Ofev for the treatment of idiopathic pulmonary fibrosis (IPF) on October 15, 2014. Ofev is one of the first FDA-approved drug treatments for IPF and the only kinase inhibitor approved to treat this disease.

The approval was based on findings from a robust clinical trial program involving more than 1,200 patients with IPF worldwide, and included the Phase II TOMORROW™ trial and the Phase III INPULSIS® trials (INPULSIS®-1 and INPULSIS®-2. All these studies were randomized, double-blind, placebo-controlled trials comparing Ofev 150 mg twice daily to placebo for 52 weeks. Both INPULSIS® trials were identically designed while the TOMORROW™ study design was similar.

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.

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 creates value through innovation for three business areas including human pharmaceuticals, animal health and biopharmaceutical contract manufacturing.

Boehringer Ingelheim is committed to improving lives and providing valuable services and support to patients and their families. Our employees create and engage in programs that strengthen our communities. Please visit www.boehringer-ingelheim.us/csr to learn more about how we make more health through our Corporate Social Responsibility initiatives.

In 2017, Boehringer Ingelheim achieved net sales of about $20.4 billion (18.1 billion euros). R&D expenditure corresponds to approximately $3.4 billion (three billion euros), or 17.0 percent of its net sales.

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

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