New Data Shows OFEV^® (nintedanib) Efficacy is Sustained Long-term with No New Safety Signals in Patients with IPF

Ridgefield, Conn., September 29, 2015 – An interim analysis of the INPULSIS^™-ON open-label extension trial of OFEV^® (nintedanib) shows efficacy and safety that is consistent to that in the two identically-designed Phase III INPULSIS^™ trials in patients with idiopathic pulmonary fibrosis (IPF). The results show no relevant changes in the safety and tolerability of OFEV. The results also suggest that treatment has a long-term effect (approximately two years) on slowing disease progression across both pivotal and open-label trials (as measured by annual rate of forced vital capacity [FVC] decline). These new data are important particularly because IPF is a rare and serious lung disease, and people with IPF may be on therapy for an extended period. The results were presented at the European Respiratory Society (ERS) International Congress 2015.

The INPULSIS^™-ON interim analysis showed that the decline in FVC at 48 weeks in patients continuing treatment with OFEV in the extension trial was comparable to what was observed in the 52 week INPULSIS^™ trials. These data support the beneficial effect of OFEV on slowing disease progression long-term in people with IPF.

“These data are significant because they provide additional evidence that OFEV maintains its safety profile and efficacy at slowing IPF disease progression over approximately two years, reinforcing the previously-reported one-year Phase III data,” said Eric White, M.D., Associate Professor of Medicine, Pulmonary and Critical Care, University of Michigan Health System. “Studies like INPULSIS^™-ON are important because they inform us about the longer-term safety and efficacy of OFEV. IPF is a chronic disease that oftentimes requires long-term treatment. Evidence that OFEV maintains its clinical effect in the absence of any new safety signals provides me with more information to discuss with my patients considering treatment with OFEV.”

Key results from the interim analysis of INPULSIS^™-ON
INPULSIS^™-ON (NCT01619085; abstract OA4495) is an open-label, single arm extension study. More than 90 percent of IPF patients participating in the identically-designed INPULSIS^™-1 and INPULSIS^™-2 trials and eligible for open-label treatment with OFEV in INPULSIS^™-ON opted to participate. Patients with IPF on placebo in the INPULSIS^™ trials (NCT01335464 and NCT01335477) initiated treatment with OFEV in the extension trial (n=304) and patients already treated with OFEV (n=430) in the INPULSIS^™ trials continued to receive treatment.

The effect of OFEV on the mean change from baseline in FVC at week 48 of the INPULSIS^™-ON trial was comparable to the one seen at 52 weeks in the INPULSIS^™ trial:

• INPULSIS^™-ON: -87 mL for all patients, -96.4 mL for patients continuing treatment with OFEV in the extension trial and -73.1 mL for patients initiating treatment with OFEV
• INPULSIS^™ (pooled data from INPULSIS^™-1 and -2): -88.9 mL (OFEV) vs. -203.0 mL (placebo)

The analysis demonstrates the effect of OFEV on slowing disease progression and provides insight into the long-term efficacy of OFEV.

No new safety signals were identified following long-term treatment with OFEV in INPULSIS^™-ON. Adverse events (AEs) were reported in 92.8 percent and 96.7 percent of patients continuing with OFEV and initiating OFEV, respectively. Serious adverse events (SAEs) were reported in 41.9 percent and 39.5 percent of these same patients. The most frequent AEs were gastrointestinal in nature with diarrhea affecting 64 percent of patients and leading to drug discontinuation in 5 percent (2.3 percent and 9.5 percent of patients continuing or initiating therapy, respectively).

“These long-term data provide evidence that the effect of OFEV persists for close to two years,” said Danny McBryan, M.D., vice president, Clinical Development and Medical Affairs, Respiratory, Boehringer Ingelheim Pharmaceuticals, Inc. “At Boehringer Ingelheim, we are committed to advancing the science of this devastating disease through our robust clinical trial program and ongoing research of OFEV in IPF patients. This continued research, and the inclusion of OFEV in the international IPF treatment guidelines, demonstrate the value of OFEV in providing important patient outcomes, particularly in slowing disease progression in IPF.”

Consistent effect of OFEV in analyses of treatment interactions
New pooled subgroup analyses from the Phase III INPULSIS^™ studies presented at the conference examined whether OFEV had a consistent effect on patients with IPF who were also taking commonly used medications, including anti-acids (abstract OA4502) and corticosteroids (abstract OA4498), when they were enrolled in the study.

Anti-acid medications are often given to patients with IPF to manage gastroesophageal reflux disease (GERD), which is common in patients with IPF and is considered to be a risk factor for IPF disease progression. IPF patients are also sometimes treated with corticosteroid medications (e.g., prednisone) and therefore those receiving low doses of corticosteroids were allowed in the INPULSIS^™ trials.

The abstracts presented at the congress can be downloaded here.

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.

IMPORTANT SAFETY INFORMATION

WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT OFEV (NINTEDANIB)?
OFEV can cause birth defects or death to an unborn baby. Women should not become pregnant while taking OFEV. Women who are able to become pregnant should use birth control during treatment and for at least 3 months after treatment. If you become pregnant while taking OFEV, tell your doctor right away.

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 diarrhea, nausea, or vomiting or if these symptoms do not go away or become worse. Tell your doctor 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. These symptoms 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. These symptoms 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 call1-800-FDA-1088.

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, or have any other medical conditions.

Tell your doctor if you are pregnant or plan to become pregnant. You should avoid becoming pregnant while taking OFEV. OFEV can cause harm, birth defects or death to your unborn baby. Use appropriate birth control methods while taking OFEV and for at least 3 months after your last dose. Tell your doctor if you 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 if you currently smoke. 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, 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.

Click here for full Prescribing Information, including Patient Information.

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.

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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