First Study Initiated to Evaluate the Effect of Ofev^® Treatment on Biomarkers that may Predict IPF Progression

Ridgefield, Conn., July 27, 2016 – Boehringer Ingelheim Pharmaceuticals, Inc. today announced the initiation of a new clinical study, INMARK^™, investigating the effect of Ofev^® (nintedanib) on specific blood biomarkers that may identify greater scarring (fibrosis) and loss of lung function in patients with idiopathic pulmonary fibrosis (IPF).

Biomarkers are substances that can be objectively measured to help predict disease prognosis. INMARK^™ will measure biomarkers that reflect substances associated with extracellular matrix (ECM) turnover, which is part of healthy tissue maintenance. However, uncontrolled or excessive turnover is a key driver for the structural change seen in IPF lungs, leading to progressive scarring and loss of lung function. By examining values and changes from baseline, it may be possible to determine those with most active fibrosis as well as describe the potential response to Ofev treatment. Furthermore, correlating biomarker concentrations with final pulmonary function tests may identify early predictors for pulmonary progression.

IPF is a debilitating and serious lung disease that causes permanent scarring of the lung tissue and loss of lung function over time. Early initiation of treatment may be crucial to help slow disease progression. Advancements have been made in the treatment of IPF with the availability of drugs such as Ofev, which has been shown to slow disease progression by reducing the decline of lung function across three clinical trials.

“Despite advances in IPF, physicians are still uncertain when to start treatment because there are differences in disease progression across IPF patients. Biomarkers may inform us on how the disease will progress in Ofev-treated patients and identify earlier response prior to showing definitive pulmonary function changes,” said Imre Noth, M.D., Professor of Medicine and Director of the Interstitial Lung Disease Program at the University of Chicago. “The INMARK^™ study may provide important insights for physicians on the impact of Ofev treatment on specific IPF biomarkers in patients with preserved lung function.”

“We are proud to initiate INMARK^™ as it is the first study to investigate the effects of an IPF treatment on biomarkers that may be predictive of IPF progression,” said Martina Flammer, M.D., vice president, Clinical Development & Medical Affairs Specialty Care, Boehringer Ingelheim Pharmaceuticals, Inc. “In a disease that displays variable rates of progression, identification of biomarkers that could allow physicians to identify and monitor individual disease progression and treatment successes in patients with IPF is essential. We hope that the identification of these biomarkers, particularly early in the disease, has the potential to improve treatment and enable better delivery of patient care.”

INMARK^™ is one of a number of new trials recently initiated by Boehringer Ingelheim to provide the scientific community with important information on the safety of Ofev in combination with other drugs and across different patient populations. This is part of Boehringer Ingelheim’s continued commitment to tackling the global burden of progressive fibrotic lung diseases.

About INMARK^™
INMARK^™ study will investigate the effect of OFEV on the rate of change of ECM turnover biomarkers compared to placebo in patients with IPF. Two thirds of patients will be treated with placebo for the first 12 weeks of the trial; one third of the patients will receive treatment with nintedanib (150 mg twice daily). Following the 12 week placebo controlled period, all patients in the trial will continue further treatment with nintedanib for 40 weeks. This will allow active treatment for patients previously on placebo. The study aims to include 350 patients across Australia, Asia, Europe and North America.

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)
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 or feeling tired. 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/medwatch or call 1-800-FDA-1088.

Click here full Prescribing Information, including Patient Information.

About 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 145 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 their 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 2015, Boehringer Ingelheim achieved net sales of about $15.8 billion (14.8 billion euros). R&D expenditure corresponds to 20.3 percent of its net sales.

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