An analysis of the Phase II TOMORROW trial and two Phase III INPULSIS trials (INPULSIS-1 and INPULSIS-2), analyzing the safety and efficacy outcomes for Ofev (nintedanib, developed by Boehringer Ingelheim), revealed that Ofev is able to slow disease progression in patients with idiopathic pulmonary fibrosis (IPF) by nearly 50 percent, as measured by the decline in forced vital capacity (FVC). Ofev was also found to reduce the risk of mortality by 30 percent, on-treatment mortality by 43 percent, and acute exacerbations by 47 percent.
The study, “Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS trials,” was published in the journal Respiratory Medicine.
Ofev (nintedanib) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of IPF in October 2014, making it one of the first IPF drug treatments, and the only kinase inhibitor, to be FDA-approved. The approval was based on the findings from the TOMORROW and INPULSIS clinical trials, which included more than 1,200 patients with IPF around the world. All studies were randomized, double-blind, placebo-controlled trials to compare Ofev 150 mg. twice a day to a placebo (723 patients were treated with Ofev and 508 with a placebo), over 52 weeks.
Overall, the meta-analysis showed that fewer patients under Ofev therapy reported an acute exacerbation — the percentage of patients with at least one acute exacerbation was 4.6 in the Ofev group and 8.7 in the placebo group. Physicians reported a reduced risk of 47 percent when compared to the placebo.
“Reducing the risk of exacerbations is an important treatment goal in the management of IPF because of their unpredictability and devastating impact on the course of the disease. Acute exacerbations often lead to death within a few months,” said the study’s lead author, Luca Richeldi, professor of respiratory medicine at the University of Southampton, England, said in a press release.
In the year-long studies, Ofev also proved favorable in all survival endpoints.
- Patients taking Ofev were 30 percent less at risk of dying from any cause when compared to the placebo;
- Patients taking Ofev were 43 percent less at risk of dying while on treatment (called on-treatment mortality), when compared to the placebo;
- Patients taking Ofev were 38 percent less at risk of dying due to an exacerbation or other respiratory cause when compared to the placebo.
The comprehensive analysis also established that Ofev did slow disease progression by about 50 percent, as measured by FVC’s annual rate of decline. Ofev’s safety and tolerability profile was also considered consistent with individual trial results.
“The analysis was consistent with individual study results showing that Ofev significantly reduces disease progression. It also shows a reduction in the risk of acute exacerbations and a trend to reduced mortality,” said Danny McBryan, vice president of Clinical Development and Medical Affairs, Respiratory, Boehringer Ingelheim Pharmaceuticals.
“As a company dedicated to respiratory care, we remain focused on continually uncovering new insights into IPF and Ofev to help support physicians as they have more informed treatment discussions with their patients,” McBryan said.
IPF is a rare and serious lung disease that causes permanent scarring of the lungs. Acute exacerbations — a sudden worsening in respiratory function without notice or apparent cause — is the leading cause of hospitalization for IPF patients. The disease is estimated to affect about 132,000 Americans, typically men, ages 65 or older. Early diagnosis and proper care are crucial for the treatment of the condition.