The results of last year's Phase 3 worldwide study using an already approved drug to see if it stopped lung fibrosis produced good results. Here is the information. (The second release regarding Pirfenidone follows.)
Phase 3 INPULSIS™ Trials Published in the New England Journal of Medicine Show Investigational Nintedanib Slowed Lung Function Loss in People with Idiopathic Pulmonary Fibrosis
RIDGEFIELD, Conn., May 18, 2014 /True Blue Tribune/ – Boehringer Ingelheim announced the results of its two pivotal Phase 3 INPULSIS™ trials (INPULSIS™-1 and -2; NCT01335464 and NCT01335477), which were published online today in the New England Journal of Medicine (NEJM). The INPULSIS™ trials evaluated the efficacy and safety of nintedanib, an investigational therapy being studied in people with idiopathic pulmonary fibrosis (IPF). The INPULSIS™ data will also be presented at the 2014 American Thoracic Society (ATS) International Conference in a joint NEJM/Journal of American Medical Association (JAMA) session on May 18 and as a late-breaking oral presentation on May 20.
IPF is a rare, progressive and fatal lung disease that causes permanent scarring of the lungs, difficulty breathing and decreases the amount of oxygen the lungs can supply to the body. IPF affects as many as 132,000 Americans. There are currently no FDA-approved treatments.
INPULSIS™-1 and -2, which involved a total of 1,061 people with IPF, met the primary endpoint: reduction in the annual rate of decline in forced vital capacity (FVC) over 52 weeks. In these trials, nintedanib reduced the annual rate of FVC decline compared to placebo by 48% in INPULSIS™-1 (-114.7 vs. -239.9 mL/year, respectively [95% CI: 77.7, 172.8]) and by 55% in INPULSIS™-2 (-113.6 vs. -207.3 mL/year, respectively [95% CI: 44.8, 142.7]).
“IPF is a very serious disease with a high unmet medical need for which there are currently no FDA-approved treatments,” said study investigator, Luca Richeldi, M.D., Ph.D., Professor of Respiratory Medicine, Chair of Interstitial Lung Disease, University of Southampton, Honorary Consultant Physician, University Hospital Southampton. “We are excited by these data because the INPULSIS™ trials suggest evidence of nintedanib’s impact on lung function loss in patients with IPF.”
In both trials, the most prevalent adverse events (AE) were gastrointestinal. Diarrhea was the most frequent AE in the nintedanib groups compared to the placebo groups, and was reported in 61.5% vs. 18.6% of participants in INPULSIS™-1 and 63.2% vs.18.3% of participants in INPULSIS™-2. Most cases were mild to moderate in intensity (93.7% in INPULSIS™-1 and 95.2% in INPULSIS™-2). In both trials, about 4.5% of people who used nintedanib discontinued treatment due to diarrhea (n=28 of 638). In these clinical trials, investigators had the option of dose reduction or dose interruption to help manage diarrhea.
Nausea was the second most common adverse event among patients treated with nintedanib versus placebo, occurring in 22.7% vs. 5.9% of participants in INPULSIS™-1 and 26.1% vs. 7.3% of participants in INPULSIS™-2.
The absolute change from baseline in FVC at 52 weeks, a pre-specified secondary endpoint, for nintedanib versus placebo was 109.9 mL in INPULSIS™-1 (-95.1 mL, nintedanib vs. -205.0 mL, placebo [95% CI: 71.3, 148.6]) and 109.8 mL in INPULSIS™-2 (-95.3 mL, nintedanib vs. -205.0 mL, placebo [95% CI: 70.9, 148.6]).
The proportion of FVC responders (i.e., categorical change), a pre-specified secondary endpoint, was also measured based on the number of patients who had an absolute decline in FVC of less than 5%, as well as an absolute decline in FVC of less than 10% at 52 weeks.
Key secondary endpoints included time to first acute exacerbation over 52 weeks and change from baseline in health-related quality of life at 52 weeks, as assessed by St. George’s Respiratory Questionnaire (SGRQ).
In INPULSIS™-2, there was a significant increase in time to first acute exacerbation in the nintedanib group compared with placebo (HR 0.38 [95% CI: 0.19, 0.77]). In addition, the proportion of patients with at least one investigator-reported acute exacerbation was lower in the nintedanib group (3.6%) compared with placebo (9.6%).
In INPULSIS™1, there was no difference between the nintedanib and placebo groups in time to first acute exacerbation (HR 1.15 [95% CI: 0.54, 2.42]), and the proportion of patients with at least one investigator-reported acute exacerbation was comparable between the nintedanib and placebo groups (6.1% vs. 5.4%, respectively).
In the pre-specified pooled analysis, there was no significant difference between nintedanib and placebo in time to first investigator-reported acute exacerbation (HR 0.64 [95% CI: 0.39, 1.05]). The proportion of patients with at least one investigator reported acute exacerbation was 4.9% in the nintedanib group versus 7.6% in the placebo group. A pre-specified sensitivity analysis based on adjudicated acute exacerbations (confirmed or suspected) in the pooled data was conducted and showed a benefit of nintedanib compared with placebo (HR 0.32 [95% CI: 0.16, 0.65]).
In INPULSIS™-2, there was a significantly smaller increase in SGRQ total score with nintedanib versus placebo at week 52, which is consistent with less deterioration in health-related quality of life (2.80 versus 5.48; difference of -2.69 [95% CI: -4.95, -0.43]). In INPULSIS™-1, there was no difference between the treatment groups in adjusted mean change from baseline at week 52 in SGRQ total score (4.34, nintedanib vs. 4.39, placebo [95% CI: -2.50, 2.40]).
“The results of the Phase 3 INPULSIS™ trials help bring us closer to our goal of delivering an effective treatment option for people in the U.S. with this progressive and fatal lung disease,” said Tunde Otulana, M.D., senior vice president, Clinical Development and Medical Affairs at Boehringer Ingelheim. “Boehringer Ingelheim has a long-standing heritage in treating respiratory diseases, and we continue to conduct important research in the rapidly evolving respiratory space. These nintedanib data exemplify our commitment to researching therapies for a variety of chronic lung diseases such as IPF.”
A higher proportion of patients in the nintedanib groups versus placebo experienced elevations in liver enzymes. In INPULSIS™-1, 15 patients (4.9%) in the nintedanib group and 1 patient (0.5%) on placebo experienced ALT and/or AST elevations of =3x ULN. In INPULSIS™-2, 17 patients (5.2%) in the nintedanib group and 2 patients (0.9%) on placebo experienced ALT and/or AST elevations of =3x ULN.
Overall, the proportions of people experiencing serious adverse events was similar in the nintedanib and placebo groups (31.1% vs. 27.0% in INPULSIS™-1; 29.8% vs. 32.9% in INPULSIS™-2, respectively). A total of 65 nintedanib patients (21.0%) and 22 (10.8%) placebo patients in INPULSIS-1 and 58 nintedanib patients (17.6%) and 33 placebo patients (15.1%) in INPULSIS-2 discontinued study medication due to adverse events.
About the Phase 3 INPULSIS™ trials (INPULSIS™-1 and INPULSIS™-2)
The double-blind, randomized and placebo-controlled trials evaluated the effect of oral nintedanib, 150 mg twice daily, on annual rate of decline in forced vital capacity FVC, in people with IPF over 52 weeks. A total of 1,061 (n=638, nintedanib vs. 423, placebo) people with IPF were enrolled in the two trials, including 513 people in INPULSIS™-1 (n=309, nintedanib vs. 204, placebo) and 548 in INPULSIS™-2 (n=329, nintedanib vs. n=219, placebo). The trials had an identical design, matched dosing, inclusion criteria, and endpoints.
The double-blind, randomized and placebo-controlled trials evaluated the effect of oral nintedanib, 150 mg twice daily, on annual rate of decline in forced vital capacity FVC, in people with IPF over 52 weeks. A total of 1,061 (n=638, nintedanib vs. 423, placebo) people with IPF were enrolled in the two trials, including 513 people in INPULSIS™-1 (n=309, nintedanib vs. 204, placebo) and 548 in INPULSIS™-2 (n=329, nintedanib vs. n=219, placebo). The trials had an identical design, matched dosing, inclusion criteria, and endpoints.
The primary endpoint was the annual rate of decline in FVC (expressed in mL over 52 weeks). There were two key secondary endpoints: change from baseline in health-related quality of life, as assessed by the SGRQ total score, and time to first acute exacerbation (days). Other secondary endpoints were respiratory mortality, overall survival, on-treatment survival, and time to death or lung transplant.
Included were people over 40 years of age with a diagnosis of IPF within five years before enrollment based on the most recent American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Latin American Thoracic Association (ALAT) IPF guideline for diagnosis and management.
Diagnosis required central review and confirmation of a combination of high resolution computerized tomography pattern and surgical lung biopsy if available.
About nintedanib
Nintedanib is an investigational small molecule tyrosine kinase inhibitor (TKI) in development by Boehringer Ingelheim for idiopathic pulmonary fibrosis (IPF). It targets growth factors, which have been shown to be potentially involved in pulmonary fibrosis — the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR).
Nintedanib is an investigational small molecule tyrosine kinase inhibitor (TKI) in development by Boehringer Ingelheim for idiopathic pulmonary fibrosis (IPF). It targets growth factors, which have been shown to be potentially involved in pulmonary fibrosis — the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR).
About idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, severely debilitating and ultimately fatal lung disease for which there are no FDA-approved treatment options in the U.S. Although lung transplantation has been shown to improve survival, the procedure is uncommon because of the limited availability of lungs for transplantation or people are either too ill or don’t survive long enough to undergo the transplant. The incidence of IPF can vary considerably and there is some evidence that the population is increasing. IPF is characterized by progressive scarring of lung tissue and loss of lung function over time. Development of scarred tissue is called fibrosis. Over time, as the tissue thickens and stiffens with scarring, the lungs lose their ability to take in and transfer oxygen into the bloodstream, and vital organs do not get enough oxygen. As a result, individuals with IPF experience shortness of breath, cough and often have difficulty participating in everyday physical activities.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, severely debilitating and ultimately fatal lung disease for which there are no FDA-approved treatment options in the U.S. Although lung transplantation has been shown to improve survival, the procedure is uncommon because of the limited availability of lungs for transplantation or people are either too ill or don’t survive long enough to undergo the transplant. The incidence of IPF can vary considerably and there is some evidence that the population is increasing. IPF is characterized by progressive scarring of lung tissue and loss of lung function over time. Development of scarred tissue is called fibrosis. Over time, as the tissue thickens and stiffens with scarring, the lungs lose their ability to take in and transfer oxygen into the bloodstream, and vital organs do not get enough oxygen. As a result, individuals with IPF experience shortness of breath, cough and often have difficulty participating in everyday physical activities.
About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, Conn., is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, Conn., 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
Here is the second release regarding Pirfenidone. If you have IPF, run not walk to your pulmonologist and discuss if this is appropriate for you. Here is the information:
IDIOPATHIC PULMONARY FIBROSIS PATIENTS TO HAVE EXPANDED ACCESS TO THERAPY
CPF Responds to InterMune’s Launch of an Expanded Access Program for Pirfenidone
For the first time in history, people suffering from the deadly lung disease idiopathic pulmonary fibrosis (IPF) will have access to a therapy. The Coalition for Pulmonary Fibrosis (CPF) commends the steps taken by the company, InterMune, Inc., to provide an Expanded Access Program (EAP) for the investigational drug, pirfenidone. The CPF represents thousands of patients suffering from the disease in the US that claims as many lives each year as breast cancer yet has limited awareness and recognition.
InterMune, Inc. announced today that the company will implement an EAP for pirfenidone. The EAP will be conducted under a treatment protocol limited to enrollment of IPF patients in the US who meet specific medical criteria.
To enroll in the EAP, a patient must be assessed by a physician who specializes in treating IPF and whose hospital or clinic center is participating in the EAP. The patient must also meet specific eligibility requirements. This means that not all physicians can provide access to pirfenidone through the EAP and not all patients who seek pirfenidone will be able to get access to it through EAP.
CPF encourages its patients with IPF to inquire about the EAP by calling InterMune Medical Information at 1-888-486-6411.
"The CPF is grateful to InterMune for its long-term commitment to the search for a PF treatment, and its willingness to extend the opportunity to access pirfenidone to an additional cohort of those who meet the enrollment requirements," said Mishka Michon, CEO of the CPF.
About Pulmonary Fibrosis (PF)
Pulmonary Fibrosis (PF) is a lung disorder characterized by a progressive scarring – known as fibrosis — and deterioration of the lungs, which slowly robs its victims of their ability to breathe. Approximately 200,000 Americans suffer from PF, and there is currently no known cause or cure. An estimated 48,000 new cases are diagnosed each year. PF is difficult to diagnose and an estimated two-thirds of patients die within five years of diagnosis. Sometimes PF can be linked to a particular cause, such as certain environmental exposures, chemotherapy or radiation therapy, residual infection, or autoimmune diseases such as scleroderma or rheumatoid arthritis. However, in many instances, no known cause can be established. When this is the case, it is called idiopathic pulmonary fibrosis (IPF).
About the CPF
The CPF is a 501C(3) nonprofit organization, founded in 2001 to accelerate research efforts leading to a cure for pulmonary fibrosis (PF), while educating, supporting, and advocating for the community of patients, families, and medical professionals fighting this disease. The CPF funds promising research into new approaches to treat and cure PF; provides patients and families with comprehensive education materials, resources, and hope; serves as a voice for national advocacy of PF issues; and works to improve awareness of PF in the medical community as well as the general public. The CPF’s nonprofit partners include many of the most respected medical centers and healthcare organizations in the U.S. With more than 28,000 members nationwide, the CPF is the largest nonprofit organization in the U.S. dedicated to advocating for those with PF. For more information please visit www.coalitionforpf.org or call (888) 222-8541.
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