INBUILD® meets primary endpoint: study evaluated Ofev® in patients across a range of progressive fibrosing interstitial lung diseases

Ridgefield, Conn., September 30, 2019 – Boehringer Ingelheim announced today that in the Phase III INBUILD® trial Ofev® (nintedanib) slowed lung function decline by 57% across the overall study population, as assessed by the annual rate of decline in forced vital capacity (FVC) over 52 weeks in patients with fibrosing interstitial lung diseases (ILDs) with signs of progression. Just published in the New England Journal of Medicine and presented at the European Respiratory Society (ERS) Congress in Madrid, Spain, the study met its primary endpoint in patients with a broad range of fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF). Nintedanib was shown to slow the rate of ILD progression independent of the fibrotic pattern seen on chest imaging. The side effect profile was consistent with previous studies of nintedanib in ILDs, with diarrhea being the most common adverse event. INBUILD is the first clinical trial in the field of ILDs to group patients based on the clinical behavior of their disease, rather than the primary clinical diagnosis.

About progressive fibrosing ILDs
ILDs encompass a large group of more than 200 disorders that may involve the threat of pulmonary fibrosis – an irreversible scarring of lung tissue that negatively impacts lung function.

Patients with ILDs can develop a progressive phenotype that causes pulmonary fibrosis, leading to lung function decline, deterioration in quality of life and early mortality similar to IPF, the most frequent form of idiopathic interstitial pneumonias. The course of the disease and the symptoms are similar in progressive fibrosis ILDs regardless of the underlying disease. Chronic hypersensitivity pneumonitis, autoimmune ILDs such as rheumatoid arthritis-associated ILD, systemic sclerosis-associated ILD (SSc-ILD), mixed connective tissue disease-associated ILD, sarcoidosis and idiopathic forms of interstitial pneumonias, i.e. non-specific interstitial pneumonia, and unclassified idiopathic interstitial pneumonia are among these diseases.

Key findings
In the INBUILD trial, nintedanib slowed lung function decline by 57% across the overall study population, with an adjusted annual rate of decline over 52 weeks in FVC of -80.8 mL/year compared to -187.8 mL/year for placebo (difference, 107.0 mL/year [95% CI, 65.4 to 148.5]; p<0.001).

The main secondary endpoints were the absolute change from baseline in King’s Brief Interstitial Lung Disease (K-BILD) health status questionnaire total score at week 52, time to acute exacerbation of ILD or death over 52 weeks, and time to death over 52 weeks. In the overall population, the change from baseline in health status at week 52 in the nintedanib and placebo groups, respectively, were 0.55 and -0.79. The proportion of patients with acute exacerbation of ILD or death over 52 weeks were 7.8% in the nintedanib group and 9.7% in the placebo group in the overall population. The proportion of patients who died over 52 weeks were 4.8% in the nintedanib group and 5.1% in the placebo group. An acute exacerbation is a sudden clinically significant deterioration in respiratory function, in many cases with unknown cause, which negatively impacts the disease course and often leads to death.

The most common adverse event was diarrhea, reported in 66.9% and 23.9% of patients treated with nintedanib and placebo, respectively, with a safety profile consistent to what has been seen in nintedanib previously. Nausea, vomiting, abdominal pain, decreased appetite and weight decrease were more frequent in the nintedanib group than the placebo group. Treatment with nintedanib was associated with elevations in liver enzymes, which normalized or showed a trend toward normalization on dose reduction, treatment interruption or discontinuation, or spontaneously.

Implications for the ILD community
“Progressive fibrosis of the lung can have a devastating impact on patients with a range of conditions. Yet, except for IPF and the new approved therapy for use in SSc-ILD in the U.S., there are currently no medications approved for the treatment of progressive fibrosing ILDs,” explained Kevin Flaherty, M.D., professor of medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan in Ann Arbor, Michigan, and lead investigator of the INBUILD trial. “The results of INBUILD showed for the first time that nintedanib slowed the decline of lung function in patients with a range of fibrosing lung diseases who demonstrate a progressive phenotype across a spectrum of ILD diagnoses.”

“We are very proud to be presenting the results of this first ever clinical trial studying patients with different forms of progressive fibrosing ILDs, which are the basis of the regulatory applications that were recently submitted with the FDA and EMA,” commented Mehdi Shahidi, M.D., chief medical officer, Boehringer Ingelheim. “We are absolutely committed to improving the lives of people living with pulmonary fibrosis, in particular those affected by rare diseases with a high level of unmet need.”

About the study
The INBUILD trial was a randomized, double-blind, placebo-controlled, parallel group trial conducted at 153 sites in 15 countries that evaluated the efficacy and safety tolerability of nintedanib (150 mg, 2 x daily) over 52 weeks in patients with progressive fibrosing ILD.

Eligible patients were aged ≥ 18 years with a physician-diagnosed ILD other than IPF and features of fibrosing lung disease of >10% extent in high-resolution computed tomography (HRCT). Patients were required to meet criteria for ILD progression within 24 months before screening, based on decline in FVC, increased fibrotic changes on imaging, or worsening of symptoms, despite treatment with drugs commonly used in clinical practice to treat ILD. A total of 663 patients, of whom 412 (62.1%) had a usual interstitial pneumonia (UIP) fibrotic pattern on HRCT, were randomized 1:1 to receive oral nintedanib 150 mg twice daily or placebo.

About Ofev
Ofev is already approved in the U.S. and more than 70 countries for the treatment of patients living with idiopathic pulmonary fibrosis (IPF) – a chronic and ultimately fatal disease characterised by a decline in lung function. It is estimated that over 80,000 people with IPF have been treated with Ofev worldwide.

In September 2019, Ofev was approved in the U.S. as the first and only therapy to slow the rate of decline in pulmonary function in patients with systemic sclerosis-associated ILD. Submissions have been made to other major regulatory bodies across the globe.

What is Ofev?

• Ofev is a prescription medicine used:
  • to treat people with a lung disease called idiopathic pulmonary fibrosis (IPF).
    ​
    or
  • to slow the rate of decline in lung function in people with systemic sclerosis-associated interstitial lung disease (SSc-ILD) (also known as scleroderma-associated ILD).
     
• 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 highly effective birth control during and for at least 3 months after your last dose. Talk with your doctor about what birth control method is right for you during this time. Women using hormonal birth control should add a barrier method of birth control (such as male condoms or spermicide). If you become pregnant or think you are 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 about all of your medical conditions, including 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.

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, and 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, feeling tired, or loss of appetite. Your doctor will do blood tests to check how well your liver is working before starting and 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 one 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, 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.

Please see full Prescribing Information, including Patient Information.

About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, Conn., is the largest U.S. subsidiary of Boehringer Ingelheim Corporation.

Boehringer Ingelheim is one of the world’s top 20 pharmaceutical companies. Headquartered in Ingelheim, Germany, the company operates globally with approximately 50,000 employees. Since its founding in 1885, the company has remained family-owned, and today our goal is to improve the lives of humans and animals through its three business areas: human pharmaceuticals, animal health and biopharmaceutical contract manufacturing.

Boehringer Ingelheim concentrates on developing innovative therapies that can improve and extend patients’ lives. As a research-driven pharmaceutical company, it plans in generations for long-term success. Its research efforts are focused on diseases with high, unmet medical need. In animal health, the company stands for advanced prevention.

In 2018, Boehringer Ingelheim achieved net sales of around $20.7 billion (17.5 billion euros). R&D expenditure of almost $3.7 billion (3.2 billion euros) corresponded to 18.1 per cent of net sales.

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