Boehringer presented its new results on the effectiveness, safety and tolerability of Ofev at ATS 2018, the American Thoracic Society’s annual conference, held in San Diego, California, May 18-23.
“The data presented at the conference support the established efficacy of Ofev, while reaffirming the safety profile observed in the clinical trials and following approval,” Christopher Corsico, MD, chief medical officer at Boehringer, said in a press release.
Scientists used data from its two Phase 3 INPULSIS trials (NCT01335477 and NCT01335464) and the Phase 2 TOMORROW study (NCT00514683) to compare the number of deaths among IPF patients treated with Ofev or placebo.
They also predicted rate of death by determining the GAP stage over one year. The GAP index is used to assess IPF prognosis and is based on gender, age, and lung function (a higher GAP is associated with an increased risk of death).
From a total of 1,228 patients, results showed fewer deaths than expected based on GAP stage in both treatment groups. Patients treated with Ofev had 46.7% of the predicted number of deaths, while those receiving placebo had 63.9%. Comparing both treatments, the data indicated that Ofev may be correlated with a 26.8% relative reduction in risk of death compared to placebo over one year.
“Treatment with nintedanib [Ofev] can slow disease progression by reducing the rate of lung function decline,” said Christopher J. Ryerson, MD, professor at the University of British Columbia Centre for Heart Lung Innovation, in Canada. “Although the individual trials were not powered to measure mortality, our pooled analysis suggests that [Ofev] may offer a survival benefit for IPF patients.”
The investigators also found that, using data from the INPULSIS trials, a greater reduction in lung function was correlated with worsened patient-reported health-related quality of life (HRQoL), comprising measures such as shortness of breath, respiratory function, cough and sputum.
Results demonstrated that a decline in forced vital capacity — a measure of lung function — greater than 10 percent predicted declines across different HRQoL measures, regardless of Ofev or placebo treatment.
“The symptoms of IPF can have a serious impact on a patient’s quality of life, resulting in a loss of independence and involvement in daily activities,” said Michael Kreuter, MD, professor at University of Heidelberg, in Germany. “Stabilizing lung function, therefore, may allow patients to retain some of their daily level of functioning, which might improve quality of life.”
Results from the largest group of Ofev-treated IPF patients analyzed to-date also confirmed the drug’s safety and tolerability. This safety analysis was done on 1,126 patients from six trials, including TOMORROW, the two INPULSIS studies, and their open-label extensions.
Ofev was given over an average of 27.7 months, with a maximum of 93.1 months. The rate of adverse events causing permanent dose reduction – from 150 mg to 100 mg, both twice daily – or treatment discontinuation were, respectively, 12.8 and 23.8 events per 100 patient exposure-years (a common measure in assessments of risk).
Diarrhea was the most frequent side effect, leading to dose reduction or treatment discontinuation in 17.2% and 8.8% of patients, respectively. This rate is lower than the one observed in the INPULSIS trials, the company noted.