OFEV® (nintedanib) Now Available in the United States

RIDGEFIELD, Conn., October 20, 2014 - Boehringer Ingelheim Pharmaceuticals, Inc. has announced that OFEV® (nintedanib) capsules are now commercially available in the United States.

OFEV was approved by the U.S. Food and Drug Administration (FDA) on October 15, 2014 for the treatment of idiopathic pulmonary fibrosis (IPF). It is the only kinase inhibitor approved to treat IPF.

IPF is a rare and fatal lung disease that affects as many as 132,000 Americans. Most people with IPF only live three to five years after diagnosis. IPF typically affects men over the age of 65.

To support the launch of OFEV, Boehringer Ingelheim has established OPEN DOORS™, a comprehensive patient support program that provides a broad range of financial and nursing support services. One of the goals of this program is to help patients who are prescribed OFEV gain rapid and affordable access to the medicine.

“We are proud to be able to offer IPF patients an effective therapy for this rare and fatal disease, together with comprehensive programs and services to support patients and healthcare providers as they begin therapy with OFEV,” said Tunde Otulana, M.D., a pulmonologist and senior vice president, Clinical Development and Medical Affairs at Boehringer Ingelheim. “Bringing a new treatment such as OFEV to patients when there is such significant unmet need is the result of many years of research and demonstrates our commitment to making a difference for patients with respiratory diseases.”

Accessible through www.OFEV.com, OPEN DOORS™ services and resources include:

• Access to support from specially-trained nurses – 24 hours a day, 7 days a week
• Assistance in finding financial resources to support access to OFEV
• Access to information about IPF and assistance in identifying local resources, such as support groups

OFEV is commercially available through specialty pharmacy distributors, as well as a select network of pharmacies. The dedicated specialty pharmacy model is intended to provide one point of contact for efficient, reliable service, and consistent product supply. Pharmacies offering OFEV were selected for their experience caring for patients with severe respiratory diseases. Selected pharmacies are uniquely positioned to offer additional services including respiratory therapy and oxygen.

About OFEV® (nintedanib) capsules

Indication and Usage

OFEV is indicated for the treatment of idiopathic pulmonary fibrosis (IPF).

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Elevated Liver Enzymes
The safety and efficacy of OFEV has not been studied in patients with moderate (Child Pugh B) or severe(Child Pugh C) hepatic impairment. Treatment with OFEV is not recommended in patients with moderate or severe hepatic impairment.

In clinical trials, administration of OFEV was associated with elevations of liver enzymes (ALT, AST, ALKP, GGT) and bilirubin. Liver enzyme increases were reversible with dose modification or interruption and not associated with clinical signs or symptoms of liver injury.

Conduct liver function tests (ALT, AST, and bilirubin) prior to treatment with OFEV, monthly for 3 months, and every 3 months thereafter, and as clinically indicated. Dosage modifications, interruption, or discontinuation may be necessary for liver enzyme elevations. 

Gastrointestinal Disorders
Diarrhea
Diarrhea was the most frequent gastrointestinal event reported in 62% versus 18% of patients treated with OFEV and placebo, respectively. In most patients, the event was of mild to moderate intensity and occurred within the first 3 months of treatment. Diarrhea led to permanent dose reduction in 11% of patients treated with OFEV compared to 0 placebo-treated patients. Diarrhea led to discontinuation of OFEV in 5% of the patients compared to <1% of placebo-treated patients.

Dosage modifications or treatment interruptions may be necessary in patients with adverse reactions of diarrhea. Treat diarrhea at first signs with adequate hydration and antidiarrheal medication (e.g., loperamide), and consider treatment interruption if diarrhea continues. OFEV treatment may be resumed at the full dosage (150 mg twice daily), or at the reduced dosage (100 mg twice daily), which subsequently may be increased to the full dosage. If severe diarrhea persists despite symptomatic treatment, discontinue treatment with OFEV.

Nausea and Vomiting
Nausea was reported in 24% versus 7% and vomiting was reported in 12% versus 3% of patients treated with OFEV and placebo, respectively. In most patients, these events were of mild to moderate intensity. Nausea led to discontinuation of OFEV in 2% of patients. Vomiting led to discontinuation of OFEV in 1% of the patients.

For nausea or vomiting that persists despite appropriate supportive care including anti-emetic therapy, dose reduction or treatment interruption may be required. OFEV treatment may be resumed at the full dosage (150 mg twice daily), or at the reduced dosage (100 mg twice daily), which subsequently may be increased to the full dosage. If severe nausea or vomiting does not resolve, discontinue treatment with OFEV.

Embryofetal Toxicity
OFEV is Pregnancy category D. It can cause fetal harm when administered to a pregnant woman. If OFEV is used during pregnancy, or if the patient becomes pregnant while taking OFEV, the patient should be advised of the potential hazard to a fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with OFEV and to use adequate contraception during treatment and at least 3 months after the last dose of OFEV.

Arterial Thromboembolic Events
Arterial thromboembolic events have been reported in patients taking OFEV. In clinical trials, arterial thromboembolic events were reported in 2.5% of patients treated with OFEV and 0.8% of placebo-treated patients. Myocardial infarction was the most common adverse reaction under arterial thromboembolic events, occurring in 1.5% of OFEV-treated patients compared to 0.4% of placebo-treated patients. Use caution when treating patients at higher cardiovascular risk including known coronary artery disease. Consider treatment interruption in patients who develop signs or symptoms of acute myocardial ischemia.

Risk of Bleeding
Based on the mechanism of action (VEGFR inhibition), OFEV may increase the risk of bleeding. In clinical trials, bleeding events were reported in 10% of patients treated with OFEV and in 7% of patients treated with placebo. Use OFEV in patients with known risk of bleeding only if the anticipated benefit outweighs the potential risk.

Gastrointestinal Perforation
Based on the mechanism of action, OFEV may increase the risk of gastrointestinal perforation. In clinical trials, gastrointestinal perforation was reported in 0.3% of patients treated with OFEV, compared to 0 cases in the placebo-treated patients. Use caution when treating patients who have had recent abdominal surgery. Discontinue therapy with OFEV in patients who develop gastrointestinal perforation. Only use OFEV in patients with known risk of gastrointestinal perforation if the anticipated benefit outweighs the potential risk.

ADVERSE REACTIONS

• Adverse reactions reported in ≥5% of patients treated with OFEV and more commonly than in patients treated with placebo included diarrhea (62% vs. 18%), nausea (24% vs.7%), abdominal pain (15% vs 6%), liver enzyme elevation (14% vs 3%), vomiting (12% vs 3%), decreased appetite (11% vs 5%), weight decreased (10% vs 3%), headache (8% vs 5%), and hypertension (5% vs 4%).
• The most frequent serious adverse reactions reported in patients treated with OFEV, more than placebo, were bronchitis (1.2% vs. 0.8%) and myocardial infarction (1.5% vs. 0.4%). The most common adverse events leading to death in patients treated with OFEV, more than placebo, were pneumonia (0.7% vs. 0.6%), lung neoplasm malignant (0.3% vs. 0%), and myocardial infarction (0.3% vs. 0.2%). In the predefined category of major adverse cardiovascular events (MACE) including MI, fatal events were reported in 0.6% of OFEV-treated patients and 1.8% of placebo-treated patients.

DRUG INTERACTIONS
P-glycoprotein (P-gp) and CYP3A4 Inhibitors and Inducers
Coadministration with oral doses of a P-gp and CYP3A4 inhibitor, ketoconazole, increased exposure to nintedanib by 60%. Concomitant use of potent P-gp and CYP3A4 inhibitors (e.g., erythromycin) with OFEV may increase exposure to nintedanib. In such cases, patients should be monitored closely for tolerability of OFEV. Management of adverse reactions may require interruption, dose reduction, or discontinuation of therapy with OFEV. Coadministration with oral doses of a P-gp and CYP3A4 inducer, rifampicin, decreased exposure to nintedanib by 50%. Concomitant use of P-gp and CYP3A4 inducers (e.g., carbamazepine, phenytoin, and St. John’s wort) with OFEV should be avoided as these drugs may decrease exposure to nintedanib.

Anticoagulants
Nintedanib is a VEGFR inhibitor, and may increase the risk of bleeding. Monitor patients on full anticoagulation therapy closely for bleeding and adjust anticoagulation treatment as necessary.

USE IN SPECIFIC POPULATIONS
Nursing Mothers

• Excretion of nintedanib and/or its metabolites into human milk is probable. Because of the potential for serious adverse reactions in nursing infants from OFEV, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Hepatic Impairment

• Monitor for adverse reactions and consider dose modification or discontinuation of OFEV as needed for patients with mild hepatic impairment (Child Pugh A). Treatment of patients with moderate (Child Pugh B) and severe (Child Pugh C) hepatic impairment with OFEV is not recommended.

Smokers

• Smoking was associated with decreased exposure to OFEV, which may alter the efficacy profile of OFEV. Encourage patients to stop smoking prior to treatment with OFEV and to avoid smoking when using OFEV.

Please click here for full Prescribing Information, including Patient Information.

Leading Respiratory Forward
Through research, treatments and patient-centric support services, the Boehringer Ingelheim (BI) lung health portfolio is designed to help address the challenges people living with a lung disease face every day. Leveraging the company's cutting edge science and leadership in chronic obstructive pulmonary disease (COPD), BI is researching new treatment approaches where needs persist. It is the company's goal to make a difference in the lives of patients with COPD, asthma, lung cancer, idiopathic pulmonary fibrosis and other respiratory diseases.

About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates and more than 47,400 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

Social responsibility is a central element of Boehringer Ingelheim's culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

In 2013, Boehringer Ingelheim achieved net sales of about $18.7 billion (14.1 billion euro). R&D expenditure in the Prescription Medicines business corresponds to 19.5% of its net sales.

For more information please visit http://www.us.boehringer-ingelheim.com

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