New Analyses Further Add to the Efficacy and Safety Profile of OFEV® (nintedanib) in Idiopathic Pulmonary Fibrosis (IPF)

Ridgefield, Conn. and Washington, D.C., November 13, 2015 – Boehringer Ingelheim Pharmaceuticals, Inc. today announced the presentation of new analyses of OFEV for the treatment of idiopathic pulmonary fibrosis (IPF) at the Pulmonary Fibrosis Foundation’s PFF Summit 2015 in Washington, D.C. In 2014, OFEV became one of the first FDA-approved drug treatments for IPF, a rare and serious lung disease that causes permanent scarring of the lungs.

In a post-marketing surveillance study in the United States, treatment with OFEV in the real-world clinical setting showed a safety profile consistent with that observed in clinical trials supporting its approval by the FDA.

“The approval of OFEV was supported by evidence from three well-designed studies part of a comprehensive clinical trial program, and it is key to continually analyze the real-world experiences of people on therapy given the limited data on IPF,” said Imre Noth, M.D., Professor of Medicine and Director of the Interstitial Lung Disease Program at The University of Chicago, and lead author of the analysis. “These first results from the post-marketing surveillance study, which showed a consistent safety profile of OFEV as described in the prescribing information, are important because they provide healthcare providers with additional information when considering OFEV for their patients with IPF.” 

First data from U.S. surveillance study
Post-marketing surveillance of the safety and tolerability of OFEV in the United States has been collected in the Boehringer Ingelheim drug safety and reporting database since OFEV was first approved on October 15, 2014. Until May 31, 2015, 3,838 people were treated with OFEV for a length of time ranging from 14 to 265 days (on average 88 days).

The most frequently reported side effects were gastrointestinal in nature and included diarrhea, nausea, vomiting and decreased appetite. Diarrhea was the most frequently reported individual side effect, occurring at a similar frequency to that observed in the clinical trials supporting approval. No new safety concerns were identified. 

Researchers also presented two post-hoc analyses from an open-label, extension of the one-year Phase III INPULSIS™ studies, known as INPULSIS™-ON. People with IPF who completed the 52-week treatment period and a four-week follow-up period in the identically-designed INPULSIS™ trials were invited to receive open-label treatment with OFEV to assess its long-term safety and tolerability. INPULSIS^®-ON included 734 participants (more than 90 percent of those completing the INPULSIS™ trials), including 304 people who initiated OFEV after receiving placebo in the Phase III trials and 430 people who were on OFEV in the INPULSIS™ trials and continued to receive treatment.

New results in people with IPF with severe lung impairment (NCT01619085)
The first analysis evaluated treatment effect in people with IPF who had severe lung impairment (less than 50 percent forced vital capacity [FVC] predicted). The Phase III INPULSIS™ studies excluded people with severe lung impairment; however, they were allowed to enter the extension study even if their lung function declined to severe levels during the initial one-year treatment period. The new analysis reports that, in patients treated with OFEV, a similar decline in lung function was observed in people with severe lung impairment when compared to people with mild to moderate impairment (greater than or equal to 50 percent predicted).

New long-term efficacy data in people with IPF (NCT01619085)
The second analysis suggests OFEV had a long-term effect on slowing FVC decline, a measure of disease progression, for approximately two years, or 100 weeks. 

Overall, the most common adverse events were diarrhea, nausea, cough, common cold (nasopharyngitis), bronchitis, difficult or labored breathing (dyspnea), IPF disease progression, decreased appetite, weight decreased and vomiting. The most frequent serious adverse event reported was IPF, which includes disease worsening and acute exacerbations.

“At Boehringer Ingelheim, we are committed to improving the understanding of IPF and the role that OFEV plays in the treatment of this disease,” said Danny McBryan, M.D., vice president, Clinical Development and Medical Affairs, Respiratory, Boehringer Ingelheim Pharmaceuticals, Inc. “Collectively, these analyses support the suggestion that OFEV continues to be effective out to approximately two years and that the decline in lung function is similar in people receiving OFEV with severe or mild to moderate impairment of lung function. These results add to our understanding of OFEV by providing insight into the impact over a longer period of time and in patients that were not included in the studies supporting its approval.”

Effect of dose reductions, treatment interruptions and dose intensity on the effect of OFEV (NCT01335464 and NCT01335477)
A fourth abstract was a post-hoc analysis of combined data from the Phase III INPULSIS™ trials among people who had to reduce OFEV dosing from 150 mg twice daily to 100 mg twice daily or interrupt treatment to manage side effects, and patients who did not have their dose modified.

The analysis showed that dose reductions or interruptions did not affect the efficacy of treatment in people with IPF. Specifically, OFEV had a similar effect on FVC decline (a measure of disease progression) irrespective of having greater than or equal to one dose reduction/interruption and less than or equal to 90 percent dose intensity. Overall, the average changes in lung function (as measured by a change in FVC from baseline to 52 weeks) were similar whether or not people had at least one dose reduction/interruption (-87.5 mL and -89.6 mL, respectively), or a reduction in dose intensity (-72.0 mL for less than or equal to 90 percent and -94.2 mL for greater than 90 percent).

About OPEN DOORS™
Boehringer Ingelheim’s patient support program, OPEN DOORS™, is a comprehensive treatment and support network to assist patients taking OFEV. Accessible through www.OFEV.com or 1-866-673-6366, OPEN DOORS™ provides a broad range of support services to people prescribed OFEV, and their caregivers, including help connecting people with IPF and their caregivers with specialty nurses who can answer questions about the disease, 24 hours a day, 7 days a week.

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.

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