New analysis confirms OFEV^® (nintedanib) slows disease progression in IPF and reduces risk of acute exacerbations

Ridgefield, Conn., February 25, 2016 – Pooled analysis from the TOMORROW and INPULSIS^® trials, recently published in Respiratory Medicine, confirmed that OFEV reduces the risk of acute exacerbations by approximately 50% in people with idiopathic pulmonary fibrosis (IPF), a rare and serious lung disease. An acute exacerbation, a sudden worsening in respiratory function without warning or known cause, is a leading cause of hospitalization for people with IPF. Around half of all people hospitalized because of an acute IPF exacerbation die during hospitalization.

The findings also showed that OFEV slowed disease progression by approximately 50% across the range of patient types in the clinical trial program*** and reduced the risk of death.

The pooled analysis is based on data from the Phase II TOMORROW trial and the two Phase III INPULSIS^® trials that included a total of 1,231 people with IPF (723 treated with OFEV, 508 treated with placebo). A separate meta analysis was conducted to summarize the data from all three trials examining OFEV efficacy and safety. Data from these three clinical trials formed the basis for the approval of OFEV in the United States, Europe, Japan and other countries worldwide.

The one-year combined data showed that:

• Fewer people overall experienced an acute exacerbation. The proportion of people with at least one acute exacerbation was 4.6% in the OFEV group and 8.7% in the placebo group. OFEV reduced the risk of an acute IPF exacerbation as reported by treating physicians by 47%, compared to placebo.
• Other study endpoints, such as forced vital capacity (FVC), were assessed in the analysis and were consistent with individual study results.

"Reducing the risk of exacerbations is an important treatment goal in the management of IPF because of their unpredictability and devastating impact on the course of the disease. Acute exacerbations often lead to death within a few months,” said Luca Richeldi, Professor of Respiratory Medicine at the University of Southampton, United Kingdom.

Over the one-year period of the studies, OFEV also showed a favorable trend in all survival endpoints:

• Compared to placebo, patients taking OFEV had a 30% reduction in the risk of dying from any cause (p=0.0954).
• Patients taking OFEV also had a 43% reduced risk of dying while on treatment (on-treatment mortality) (p=0.0274).
• A 38% reduction in the risk of death because of an exacerbation or other respiratory cause versus placebo (p=0.0779).

The analysis also confirmed that OFEV slowed disease progression by approximately 50%, as measured by annual rate of decline in FVC. The overall adjusted annual rate of decline in FVC was −112.4 mL/year with OFEV and −223.3 mL/year with placebo (difference: 110.9 mL/year). The safety and tolerability profile of OFEV in the pooled analysis was consistent with results of the individual TOMORROW and the INPULSIS^® trials.

“The analysis was consistent with individual study results showing that OFEV significantly reduces disease progression. It also shows a reduction in the risk of acute exacerbations and a trend to reduced mortality,” said Danny McBryan, M.D., vice president, Clinical Development and Medical Affairs, Respiratory, Boehringer Ingelheim Pharmaceuticals, Inc. “As a company dedicated to respiratory care, we remain focused on continually uncovering new insights into IPF and OFEV to help support physicians as they have more informed treatment discussions with their patients.”

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 OFEV^® (nintedanib) capsules
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 (NCT00514683) and the Phase III INPULSIS^™ trials (INPULSIS^™-1 and INPULSIS^™-2; NCT01335464 and NCT01335477). 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 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
• are a smoker. You should stop smoking prior to taking OFEV and avoid smoking during treatment.
• have 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 and your doctor should decide if you will take OFEV or breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements such as St. John’s wort.  Keep a list of the medicines you take and show it to your doctor and pharmacist when you get a new medicine.

What are the possible side effects of OFEV?

OFEV may cause serious side effects, including:

• Liver problems. Call your doctor right away if you have unexplained symptoms such as 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 or feeling tired. Your doctor will do blood tests regularly to check how well your liver function is working during your treatment with OFEV.
• Diarrhea, nausea, and vomiting. Tell your doctor if you have these symptoms or if they do not go away or become worse and if you are taking over-the-counter laxatives, stool softeners, and other medicines or dietary supplements that can cause diarrhea.  While you are taking OFEV, your doctor may recommend that you drink fluids or take medicine to treat these side effects. 
• Heart attack. Tell your doctor right away if you have symptoms of a heart problem which may include chest pain or pressure, pain in your arms, back, neck or jaw, or shortness of breath.
• Stroke. Tell your doctor right away if you have symptoms of a stroke which 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. Tell your doctor 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/medwatch or call 1-800-FDA-1088.

Click here for full Prescribing Information, including Patient Information.

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

Boehringer Ingelheim is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, the company operates globally with 146 affiliates and more than 47,000 employees. Since its founding in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel treatments for human and veterinary medicine.

Boehringer Ingelheim is committed to improving lives and providing valuable services and support to patients and families. Our employees create and engage in programs that strengthen our communities. To learn more about how we make more health for more people, visit our Corporate Social Responsibility Report.

In 2014, Boehringer Ingelheim achieved net sales of about $16.96 billion dollars (13.3 billion euros). R&D expenditure corresponds to 19.9 percent of its net sales.

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

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