The analyis, conducted by an international research team, was published in the journal BMJ Open Respiratory Research, in an article titled “Safety and survival data in patients with idiopathic pulmonary fibrosis treated with nintedanib: pooled data from six clinical trials.”
Ofev (marketed by Boehringer Ingelheim in the U.S., and as Vargatef in the E.U.) is an inhibitor of tyrosine kinases, which are important mediators of several growth factor signals known to be involved in IPF. The therapy was approved in October 2014 by the U.S. Food and Drug Administration, and in January 2015 by the European Medicines Agency for the treatment of IPF.
The decision to approve the therapy was supported by results of several controlled Phase 2 and 3 clinical trials. These included the Phase 2 TOMORROW trial (NCT00514683) and its open-label extension (NCT01170065), the two replicate Phase 3 INPULSIS trials (NCT01335464 and NCT01335477) and their open-label extension INPULSIS-ON (NCT01619085), and also an exploratory Phase 3b study (NCT01979952).
These trials demonstrated that treatment with Ofev could significantly prevent disease progression by slowing the rate of decline in forced vital capacity — a measure of lung function — in IPF patients.
Although these studies were not designed to evaluate the impact of the treatment on a patient’s survival, the data suggested that Ofev could reduce the risk of death by 30% compared with a placebo over 52 weeks of treatment.
To further explore Ofev’s effects, an international research team conducted a new analysis of the pooled data of these clinical trials. The analysis included data collected from a total of 1,126 IPF patients (mean age of 66.9 years), who were treated twice daily with 150 mg of Ofev, and 565 patients treated with a placebo.
Participants received the treatment for a mean period of 27.7 months, with some patients receiving the treatment for a maximum of 93.1 months. In comparison, patients in the placebo group received a non-active compound for shorter periods of time, with a mean exposure of 10.4 months, up to a maximum of 13.1 months.
Based on the trials’ clinical data, the researchers were able to estimate patients’ survival, which was found to be significantly extended with Ofev treatment compared with a placebo. Patients treated with Ofev had an estimate mean survival of 11.6 years, which was approximately three times longer than that predicted for patients treated with a placebo (3.7 years).
“Exploratory analyses based on extrapolation of survival data suggested that patients with IPF who are treated with nintedanib have longer life expectancy than those who do not receive treatment,” the researchers wrote.
The most common adverse events from Ofev treatment were bleeding, major adverse cardiovascular events, myocardial infarction, and increased liver enzyme levels.
Diarrhea was the most frequent side effect among patients treated with Ofev, with a higher incidence than in the pooled placebo group. Also, diarrhea was the most frequent side effect that led to permanent Ofev dose reduction or treatment discontinuation.
“Based on pooled data from six clinical trials, the adverse event profile of nintedanib was manageable for most patients,” the researchers wrote. They emphasized, however, that the medication should be taken by patients with a known risk of bleeding “only if the anticipated benefit outweighs the potential risk.”
To manage the effects of diarrhea while taking Ofev, the team recommended that patients should “ensure adequate hydration and take antidiarrheal medicine.”
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