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A deluge of data
RIDGEFIELD, Conn.—The last few months have been busy ones for Boehringer Ingelheim, as it has had results and analyses to share for several of its ongoing clinical trials. The bulk of the news has come from the company’s efforts in pulmonary diseases and conditions—including asthma, idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (CODP)—but the pharma giant has also had progress to tout in its cancer-fighting efforts as well.
At this year’s CHEST meeting, the company presented a pair of post-hoc pooled analyses of the Phase 3 INPULSIS trials that offered additional support for the efficacy of Ofev (nintedanib) in a variety of people with IPF, regardless of disease severity at the beginning of the trials. INPULSIS-1 and -2 are two identical Phase 3 trials focused on the safety and efficacy of Ofev in treating IPF. The drug received U.S. Food and Drug Administration approval for the treatment of IPF on Oct. 15, 2014, and is the only kinase inhibitor approved for treating IPF.
“Understanding how treatment will affect disease progression for patients who begin drug therapy at different severity levels is critical to helping pulmonologists make treatment decisions,” said Luca Richeldi, professor of respiratory medicine at the University of Southampton in the United Kingdom. “Both of these analyses demonstrated a consistent clinical effect with Ofev in patients irrespective of the severity of IPF at treatment initiation.”
The pooled analysis looked at Ofev’s efficacy in terms of disease progression in patients grouped by their GAP (gender, age, physiology) stage; at baseline, 500 patients were at GAP stage I, and 560 were at GAP stage II/III. Patients saw similar reductions in disease progression with Ofev compared to placebo regardless of GAP stage. Treatment effect remained constant for the two GAP groups when progression was measured as an absolute forced vital capacity decline ≥10 percent predicted or death over 52 weeks.
Another post-hoc pooled analysis of the trials examined the effect of treatment on disease progression based on patients’ baseline composite physiologic index (CPI), which reflects disease severity through spirometric volumes and measures of gas transfer without radiologic scoring. The analyses looked at patients with regards to baseline CPI of ≤45 versus >45, and ≤55 versus >55, with a higher CPI score associated with a worse prognosis. At baseline, 462 patients had CPI ≤45 and 598 had CPI >45; 829 patients had CPI ≤55 and 231 had CPI >55.
With the baseline CPI threshold of 45, treatment effects were comparable based on the time to absolute decline in FVC ≥5 percent predicted or death over 52 weeks or the time to absolute decline in FVC ≥10 percent predicted or death over 52 weeks. No significant differences in treatment effect were seen when a baseline CPI threshold of 55 was used to define subgroups for time to absolute decline in FVC ≥5 percent or death and for time to absolute decline in FVC ≥10 percent or death.
In September, the company shared study results from its Phase 3 CanoTinA-asthma trial demonstrating that adding tiotropium Respimat, an inhaled long-acting anticholinergic bronchodilator, to maintenance asthma therapy in children ages 6 to 11 significantly improved lung function. The trial consisted of children who were already using an inhaled corticosteroid (ICS) or an ICS together with other maintenance therapy.
A pooled analysis from four studies—VivaTinA-asthma, RubaTinA-asthma, PensieTinA-asthma and CanoTinA-asthma—demonstrated that adding tiotropium Respimat to maintenance therapy for children aged 6-17 years has a comparable safety profile to placebo. In children ages 1 to 5, adding the therapeutic to maintenance therapy saw a safety profile consistent with that seen in older children and adults.
At the same time, Boehringer Ingelheim shared two sets of news for patients with COPD. The company released the first results from its Phase 3b/4 PHYSACTO trial, which showed that Stiolto Respimat, together with exercise training, helped COPD patients walk for longer periods of time compared to those on placebo. In fact, participants in that trial arm saw their exercise capacity increase by 45.8 percent compared to those on placebo. Even without exercise training, participants in the tiotropium+olodaterol Respimat arm saw significant improvement in their exercise capacity, to the tune of a 29.2-percent increase in shuttle walk duration compared to placebo.
In a post-hoc subanalysis of its WISDOM study, Boehringer Ingelheim found that only four out of 100 people with COPD and a history of frequent exacerbations and raised eosinophil levels are likely to see further benefit from adding ICS to Spiriva (tiotropium) and a long-acting beta2-agonist (LABA) in terms of reducing their exacerbation risk.
COPD exacerbations are a significant contributor to the disease’s impact. The Global Initiative for Chronic Obstructive Lung Disease (GOLD), a collaboration between the World Health Organization and the National Institutes of Health, recommends the use of ICS-containing therapy only in COPD patients with severe to very severe lung function impairment and/or who are at high risk of exacerbations or who have had a hospitalization (which comprised the WISDOM patient population). ICS are commonly used outside of GOLD treatment recommendations together with bronchodilators, such as tiotropium and LABAs, to treat COPD.
“New results from the WISDOM study indicate that using ICS as part of a triple therapy regimen in COPD maintenance treatment reduces the likelihood of an exacerbation for a smaller number of people than previously thought. It challenges our current understanding of the appropriate use of ICS in COPD maintenance therapy,” said Prof. Peter Calverley, professor of pulmonary medicine at the University of Liverpool and a study investigator. “These study results add important information to a debate that has potentially wide-ranging implications for the future treatment of people with COPD.”
Boehringer Ingelheim’s cancer efforts have included a focus on team-ups for clinical development or trials. Among other announcements, the company shared news in October that it would be joining The Leukemia & Lymphoma Society (LLS) in a first-of-its-kind collaborative trial program to advance treatments for acute myeloid leukemia (AML) patients: the Beat AML Master Trial. This undertaking will assess investigational medicines from a number of biopharmaceutical companies and enroll newly diagnosed patients, which will be assigned to treatment arms based on their genomic analysis. Of those treatment arms, one will include BI 836858, Boehringer Ingelheim’s investigational anti-CD33 monoclonal antibody.
The Beat AML Master Trial is hoping to adjust the current standard for how this cancer type is treated, specifically by taking a precision medicine approach. Genomic technology will be used to find and match patients’ specific AML mutations with the investigational drug(s) best suited to target those mutations.
This initiative will launch at five leading cancer centers: The Ohio State University, Memorial-Sloan Kettering Cancer Center, Oregon Health and Science University, Dana-Farber Cancer Institute and Massachusetts General. It is anticipated that the first patients will be enrolled this month, with six additional sites prepared to start enrolling patients in April 2017. The eventual goal is to expand this effort to between 15 and 20 sites, with up to 10 treatment arms and 500 patients. Other collaborators in the Beat AML Master Trial include Foundation Medicine, INC Research, Protocol First, MyClin, Alexion, Celgene and Gilead.
“This is a unique opportunity to put the interests of a particularly underserved patient population front and center by bringing multiple biopharmaceutical companies with investigational medicines targeting AML together,” Dr. Martina Flammer, vice president of Clinical Development & Medical Affairs Specialty Care at Boehringer Ingelheim, remarked. “Boehringer Ingelheim is proud to join other leading experts and medical centers to take part in this pioneering initiative.”
Boehringer Ingelheim kicked off another cancer-focused partnership around the same time, this one a strategic collaboration with the Sarah Cannon Research Institute, the research arm of Sarah Cannon, the global cancer institute of HCA. The goal is to bring innovative cancer treatments to patients with unmet medical needs, specifically novel immune-oncology therapies. Through this joint clinical development program, the two organizations will study BI 754091 (anti-PD-1) and BI 754111 (anti-LAG 3), monoclonal antibodies from Boehringer Ingelheim indicated for the combination treatment of multiple cancers, including non-small cell lung cancer. Depending on preliminary findings, the collaboration could expand to include other areas or targets of interest.