GilotrifTM (afatinib) tablets will be available in the U.S. the week of September 2

Ridgefield, CT, August 22, 2013 – Boehringer Ingelheim Pharmaceuticals, Inc. has announced that GilotrifTM (afatinib) tablets for oral use will be commercially available in the U.S. the week of September 2.

The U.S. Food and Drug Administration (FDA) approved GILOTRIF on July 12, 2013 as a new first-line – or initial – treatment for patients with metastatic non-small cell lung cancer (NSCLC) with common epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test. Safety and efficacy of GILOTRIF have not been established in patients whose tumors have other EGFR mutations.

Supporting Patient Access to GILOTRIF
Boehringer Ingelheim has established a comprehensive patient support program that will provide a broad range of access and clinical support solutions, including financial support services. One of the goals of this program, called Solutions Plus™, is to help patients who are prescribed GILOTRIF gain access to the medicine quickly and affordably. More information can be provided by calling a Solutions Plus™ Patient Care Advocate at 1-877-814-3915 or by visiting www.bisolutionsplus.com.

Until GILOTRIF becomes commercially available, eligible patients in need of afatinib may be enrolled in the Expanded Access Program (EAP); at the time of availability, Boehringer Ingelheim will provide support to healthcare professionals and patients to ensure a smooth transition. Healthcare professionals and patients can learn more about the EAP by calling 1-855-EAP-BIPI (855-327-2474) or by visiting clinicaltrials.gov.

About metastatic NSCLC and EGFR Mutations
In some people, genetic mutations lead to the constant activation of the EGFR protein, which is associated with uncontrolled cell division and the development and progression of NSCLC. Among patients diagnosed with NSCLC (the most common form of lung cancer), it is estimated that between 10 and 15 percent of Caucasians and approximately 40 percent of Asians have EGFR mutations – which in 90 percent of cases are one of the two most common EGFR mutations (Del19 or L858R).

To determine if a patient is eligible for GILOTRIF, physicians must conduct a test for genetic mutations – also known as biomarker testing – to determine if a common EGFR mutation is present. For this reason, and in line with FDA’s current guidance, Boehringer Ingelheim collaborated with QIAGEN, a leading global provider of sample and assay technologies, on the development of a companion diagnostic for GILOTRIF. QIAGEN’s therascreen® EGFR RGQ PCR Kit was reviewed and approved by the FDA in parallel to GILOTRIF and will be used to identify patients who may be eligible for treatment. For more information about the FDA-approved therascreen® EGFR RGQ PCR Kit, please contact QIAGEN at 1-240-686-7425.

About GILOTRIF
GILOTRIF is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.

Limitation of Use: Safety and efficacy of GILOTRIF have not been established in patients whose tumors have other EGFR mutations.

GILOTRIF is an oral, once-daily kinase inhibitor that is designed to irreversibly bind and inhibit the following receptors: EGFR (ErbB1), HER2 (ErbB2) and ErbB4.

IMPORTANT SAFETY INFORMATION  

WARNINGS AND PRECAUTIONS
Diarrhea

  • Diarrhea has resulted in dehydration with or without renal impairment; some of these cases were fatal. In the pivotal study, diarrhea occurred in 96% of patients treated with GILOTRIF (n=229), of which 15% was Grade 3 in severity and occurred within the first 6 weeks. Renal impairment as a consequence of diarrhea occurred in 6.1% of patients treated with GILOTRIF, out of which 3 (1.3%) were Grade 3.
  • For patients who develop prolonged Grade 2 diarrhea lasting more than 48 hours or greater than or equal to Grade 3 diarrhea, withhold GILOTRIF until diarrhea resolves to Grade 1 or less, and resume GILOTRIF with appropriate dose reduction. 

Bullous and Exfoliative Skin Disorders

  • Grade 3 cutaneous reactions characterized by bullous, blistering, and exfoliating lesions occurred in 6 (0.15%) of the 3865 patients who received GILOTRIF across clinical trials. In the pivotal study, the overall incidence of cutaneous reactions consisting of rash, erythema, and acneiform rash was 90%, and the incidence of Grade 3 cutaneous reactions was 16%.  In addition, the incidence of Grade 1-3 palmar-plantar erythrodysesthesia syndrome was 7%. Discontinue GILOTRIF in patients who develop life-threatening bullous, blistering, or exfoliating lesions.  For patients who develop prolonged Grade 2 cutaneous adverse reactions lasting more than 7 days, intolerable Grade 2, or Grade 3 cutaneous reactions, withhold GILOTRIF until the adverse reaction resolves to Grade 1 or less, and resume GILOTRIF with appropriate dose reduction.

Interstitial Lung Disease (ILD)

  • ILD or ILD-like adverse reactions (e.g., lung infiltration, pneumonitis, acute respiratory distress syndrome, or alveolitis allergic) occurred in 1.5% of the 3865 patients who received GILOTRIF across clinical trials; of these, 0.4% were fatal. The incidence of ILD appeared to be higher in patients of Asian ethnicity (2.1%) as compared to non-Asians (1.2%).  In the pivotal study, the incidence of Grade ≥3 ILD was 1.3% and resulted in death in 1% of GILOTRIF-treated patients.
  • Withhold GILOTRIF during evaluation of patients with suspected ILD, and discontinue GILOTRIF in patients with confirmed ILD.

Hepatic Toxicity

  • In 3865 patients who received GILOTRIF across clinical trials, 10.1% had liver test abnormalities, of which 7 (0.18%) were fatal.  In the pivotal study, liver test abnormalities of any grade occurred in 17.5% of the patients treated with GILOTRIF.
  • Obtain periodic liver testing in patients during treatment with GILOTRIF. Withhold GILOTRIF in patients who develop worsening of liver function. In patients who develop severe hepatic impairment while taking GILOTRIF, treatment should be discontinued.

Keratitis

  • Keratitis, characterized as acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, and/or red eye occurred in 0.8% of patients treated with GILOTRIF among 3865 patients across clinical trials. Keratitis was reported in 5 (2.2%) patients in the pivotal study, with Grade 3 in 1 (0.4%).  Withhold GILOTRIF during evaluation of patients with suspected keratitis, and if diagnosis of ulcerative keratitis is confirmed, treatment with GILOTRIF should be interrupted or discontinued. If keratitis is diagnosed, the benefits and risks of continuing treatment should be carefully considered. GILOTRIF should be used with caution in patients with a history of keratitis, ulcerative keratitis, or severe dry eye. Contact lens use is also a risk factor for keratitis and ulceration.

Embryofetal Toxicity

  • GILOTRIF is Pregnancy Category D. Based on its mechanism of action, GILOTRIF can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
  • Advise females of reproductive potential to use highly effective contraception during treatment, and for at least 2 weeks after the last dose of GILOTRIF. Advise patients to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking GILOTRIF.

ADVERSE REACTIONS

  • The most common adverse reactions (≥20%) in the GILOTRIF-treated patients (n=229) in the pivotal study were diarrhea, rash/dermatitis acneiform, stomatitis, paronychia, dry skin, decreased appetite, pruritus.
  • Serious adverse reactions were reported in 29% of patients treated with GILOTRIF. The most frequent serious adverse reactions reported in patients treated with GILOTRIF were diarrhea (6.6%); vomiting (4.8%); and dyspnea, fatigue, and hypokalemia (1.7% each). Fatal adverse reactions in GILOTRIF-treated patients included pulmonary toxicity/ILD-like adverse reactions (1.3%), sepsis (0.43%), and pneumonia (0.43%).
  • More GILOTRIF-treated patients (2.2%; n=5) experienced ventricular dysfunction (defined as diastolic dysfunction, left ventricular dysfunction, or ventricular dilation; all < Grade 3) compared to chemotherapy-treated patients (0.9%; n=1).

DRUG INTERACTIONS
Effect of P-glycoprotein (P-gp) Inhibitors and Inducers

  • Concomitant taking of P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) with GILOTRIF can increase exposure to afatinib.
  • Concomitant taking of P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital, and St. John’s wort) with GILOTRIF can decrease exposure to afatinib.

USE IN SPECIFIC POPULATIONS
Nursing Mothers

  • It is not known whether afatinib is present in human milk.  Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from GILOTRIF, 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.

Renal Impairment

  • GILOTRIF has not been studied in patients with severely impaired renal function. Closely monitor patients with moderate (CLcr 30-59 mL/min) to severe (CLcr <30 mL/min) renal impairment and adjust GILOTRIF dose if not tolerated.

Hepatic Impairment

  • GILOTRIF has not been studied in patients with severe (Child Pugh C) hepatic impairment. Closely monitor patients with severe hepatic impairment and adjust GILOTRIF dose if not tolerated.

For full GILOTRIF prescribing information, including Patient Information, please visit www.gilotrif.com or contact Boehringer Ingelheim's Medical and Technical Information (MTI) Unit at 1-800-542-6257.

About Boehringer Ingelheim in Oncology
Building on scientific expertise and excellence in the fields of pulmonary and cardiovascular medicine, metabolic disease, neurology, virology and immunology, Boehringer Ingelheim has embarked on a major research program to discover and develop innovative cancer treatments.  Working in close collaboration with the international scientific community and a number of the world’s leading cancer centers, Boehringer Ingelheim’s commitment to oncology is underpinned by using advances in science to develop a range of targeted therapies for various solid tumors and hematological cancers. The current focus of late-stage research includes compounds in three areas: signal transduction inhibition, angiogenesis inhibition and cell-cycle kinase inhibition. The company is also evaluating a robust and growing pipeline of early-stage oncology compounds in areas including growth/survival signaling, immunotherapy and epigenetics.

For information about participating in a Boehringer Ingelheim clinical trial, please visit www.bicancertrials.com or call 1.866.725.7110. Healthcare providers interested in learning more about Boehringer Ingelheim clinical trials in oncology can visit www.inoncologyus.com for additional information. 

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 140 affiliates and more than 46,000 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 2012, Boehringer Ingelheim achieved net sales of about $19.1 billion (14.7 billion euro). R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales.

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

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