New analysis of INPULSIS^™ trials demonstrates efficacy of OFEV^® (nintedanib) across a range of IPF patients using broader diagnostic criteria

Ridgefield, Conn., June 27, 2016 – New analysis of the INPULSIS^™ trials show for the first time that disease progression is similar in idiopathic pulmonary fibrosis (IPF) patients identified using a broader diagnostic definition compared with the current diagnostic guidelines. The post-hoc analysis of these 1,061 patients has now been published in the American Journal of Respiratory and Critical Care Medicine.

IPF is a devastating and fatal condition. Physicians use an imaging technique called high resolution computed tomography (HRCT) to help them identify the presence of scarring (fibrosis) and specifically the presence of usual interstitial pneumonia (UIP) pattern in the lungs to ensure an accurate diagnosis of IPF. Radiological changes called “honeycombing” are a key indicator for lung fibrosis and a feature of the UIP pattern visible on HRCT. However, it can be challenging to confirm that scarring in the absence of honeycombing on HRCT that meets the strict guideline criteria for a definitive diagnosis of IPF. For a large group of patients who do not receive a confirmed diagnosis of IPF according to guidelines, including those not eligible for surgical lung biopsy, the clinical course of their condition and the effectiveness of IPF treatment remains unknown. Investigations into the behavior of the disease across diagnostic subgroups is therefore crucial.

The INPULSIS trials included patients with a classic diagnosis of IPF but also those patients with a clinical diagnosis of IPF who, in the absence of a surgical lung biopsy and honeycombing on HRCT, had a possible UIP pattern and the presence of traction bronchiectasis. Traction bronchiectasis is recognized as one of the most relevant CT signs of lung fibrosis. The analysis also shows that OFEV^® is effective in slowing disease progression in both diagnostic subgroups which confirms the efficacy of OFEV across a broad range of IPF patient types studied in Phase III and may be applicable to patients seen in clinical practice.

“In clinical practice, achieving a confident diagnosis of IPF is complex. While the accuracy of IPF diagnosis is increased by discussions among experts from multi-disciplinary services at regional centers with expertise in interstitial lung diseases, community physicians may more often make a diagnosis of IPF that does not always meet the criteria laid down by international guidelines,” said Ganesh Raghu, M.D., Professor of Medicine, University of Washington in the Division of Pulmonary and Critical Care Medicine and Director of Center for Interstitial Lung Diseases at University of Washington Medical Center, Seattle, Washington. “This analysis confirms for the first time that disease progression and effect of treatment in a subgroup of patients not fully meeting the diagnostic criteria is similar to those meeting the current criteria, as defined in the 2011 international guidelines for diagnosis of IPF. This has implications to consider accepting the modified criteria, as used in this study for making a diagnosis of IPF that includes presence of possible UIP pattern and traction bronchiectasis in lower lobes (despite the absence of definite honeycombing on HRCT and surgical lung biopsy), in an appropriate clinical setting and in future clinical trials.”

The subgroup analysis showed that:

• In patients with confirmed UIP pattern, including honeycombing and/or biopsy, the adjusted annual rate of decline in FVC was −108.7 mL/year in the nintedanib group and -225.7 mL/year in the placebo group (difference versus placebo of 117.0 mL/year).
• In patients with HRCT features of possible UIP pattern, with no honeycombing and no biopsy but the presence of traction bronchiectasis, the adjusted annual rate of decline in FVC was −122.0 mL/year in the nintedanib group and -221.0 mL/year in the placebo (difference versus placebo of 98.9 mL/year).
• The treatment-by-subgroup interaction p-value was not significant (p=0.8139), indicating that the treatment effect of nintedanib was not different between the subgroups.
• The treatment effect in both subgroups was also consistent with the treatment effect in the overall pooled population.
• Adverse events were similar between subgroups.

For more information on the current international guidelines and diagnostic criteria please visit: http://www.atsjournals.org/doi/full/10.1164/rccm.2009-040GL#.VyMb-fkrLIU

About the Study
A total of 1,061 patients were included in the post-hoc subgroup analysis by diagnostic criteria of pooled data from the phase III INPULSIS trials. All the patients in the INPULSIS trials had a diagnosis of IPF established in clinical practice ≤5 years before randomization. For the purpose of the subgroup analysis 31.9% of patients were classified as having a possible UIP pattern with traction bronchiectasis on HRCT and have not undergone a surgical lung biopsy and 68.1% patients as having either UIP pattern on HRCT and/or surgical lung biopsy confirming UIP pattern (the diagnosis of IPF according to current international guidelines).

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.

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 full Prescribing Information, including Patient Information. 

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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.

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