Efficacy of Ofev^® (nintedanib) Reinforced in Range of Patients with IPF in New Analyses Presented at CHEST

Ridgefield, Conn., October 24, 2016 – At CHEST 2016, two post-hoc pooled analyses of the Phase III INPULSIS^® trials were presented that further demonstrate the efficacy of Ofev^® (nintedanib) in a range of people with idiopathic pulmonary fibrosis (IPF), regardless of disease severity at the start of the trials. IPF is a rare and serious lung disease causing permanent scarring of the lungs, typically affecting men over the age of 65.

“Understanding how treatment will affect disease progression for patients who begin drug therapy at different severity levels is critical to helping pulmonologists make treatment decisions,” said Luca Richeldi, Professor of Respiratory Medicine at the University of Southampton, United Kingdom. “Both of these analyses demonstrated a consistent clinical effect with Ofev in patients irrespective of the severity of IPF at treatment initiation.”

Pooled analysis of the two Phase III INPULSIS^® trials investigated the efficacy of Ofev on disease progression in subgroups of patients defined by their GAP (gender, age, physiology) stage. GAP stage is a composite index developed to predict prognosis in patients with IPF. Based on the index, patients were categorized as either GAP stage I or II/III. At baseline, 500 patients (nintedanib 304; placebo 196) were at GAP stage I, and 560 patients (nintedanib 334; placebo 226) were at GAP stage II/III.

The analysis showed a similar reduction in disease progression with Ofev versus placebo regardless of GAP stage (no significant difference between GAP stage I versus GAP stage II/III). Disease progression was defined as an absolute decline in forced vital capacity (FVC) ≥5% predicted or death over 52 weeks. In addition, treatment effect remained consistent between the two GAP subgroups when progression was measured as an absolute FVC decline ≥10% predicted or death over 52 weeks.

A second post-hoc pooled analysis of the two Phase III INPULSIS^® trials investigated the effect of treatment on disease progression based on patients’ baseline composite physiologic index (CPI), a newer measure that also reflects disease severity through the use of spirometric volumes and measures of gas transfer without radiologic scoring. Subgroup analyses were conducted of patients by baseline CPI of ≤45 versus >45, and ≤55 versus >55. A higher CPI score is associated with a worse prognosis. At baseline, 462 patients (nintedanib 278; placebo 184) had CPI ≤45 and 598 (nintedanib 360; placebo 238) had CPI >45; 829 patients (nintedanib 509; placebo 320) had CPI ≤55 and 231 (nintedanib 129; placebo 102) had CPI >55.

When using the baseline CPI threshold of 45, treatment effects were comparable based on the time to absolute decline in FVC ≥5% predicted or death over 52 weeks (≤45 vs. >45) or the time to absolute decline in FVC ≥10% predicted or death over 52 weeks. Also, there were no significant differences in treatment effect when a baseline CPI threshold of 55 was used to define subgroups for time to absolute decline in FVC ≥5% or death and for time to absolute decline in FVC ≥10% or death.

The corresponding abstracts can be found within the online program, here: http://chestmeeting.chestnet.org/Program/CHEST-2016-Program

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. The INPULSIS^®-ON (Clinicaltrial.gov trial identifier: NCT01619085) trial included 734 patients and is currently ongoing.

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 for 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.

PC-OF-0141-PR