Long-term treatment with Boehringer Ingelheim‘s Ofev (nintedanib) improved the lung function and reduced the flare-ups of people with idiopathic pulmonary fibrosis, results of a Phase 2 clinical trial and its extension show.
The study, “Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: results from the TOMORROW trial and its open-label extension,” appeared in the journal Thorax.
IPF is a progressive lung disease with a median survival rate of only three years after diagnosis.
The Phase 2 TOMORROW trial (NCT00514683) evaluated Ofev’s safety and effectiveness in two periods.
Period 1 covered 52 weeks. The 428 patients in the randomized, placebo-controlled study received one of four doses of Ofev.
Two hundred eighty-six patients participated in the Period 2 study. The length of their participation varied. That’s because the trial design called for Period 2 to continue until the last patient in Period 1 had completed 52 weeks of treatment.
Patients who completed Period 2 could then participate in an open-label extension trial (NCT01170065) of Ofev. One hundred ninety-eight patients started the extension study.
Boehringer Ingelheim had shown in a preliminary analysis of the TOMORROW results that 150 mg of Ofev twice a day reduced patients’ annual decline in forced vital capacity. FVC is the amount of air a person can exhale quickly after taking a deep breath.
The latest analysis showed Ofev’s long-term benefits. Researchers said the annual rate of lung-function decline was much lower among patients who took Ofev throughout the Phase 2 trial and its extension than among those who received a placebo during Period 1 of the trial, Ofev during Period 2, and Ofev during the extension.
This was true even though the group that started with the placebo in Period 1 received only 50 mg of Ofev once a day in Period 2, versus 150 mg twice day in the group that started with Ofev in Period 1. The Period 1 placebo group had a choice of going to 150 mg twice a day during the extension, however.
Another important finding was that Ofev lowered the risk of flare-ups, or acute exacerbations, by 47 percent over the long term and the risk of patients’ death from all causes by 30 percent.
Ofev’s adverse effects have also remained consistent throughout the trials.
Researchers said one of the limitations of the long-term Phase 2 trial and extension was the shift in some patients’ treatment between a placebo and Ofev. Another limitation was different Ofev doses that prevented statistical comparisons between groups.
Still another limitation was lack of a true placebo group — since some patients were shifted from a placebo to Ofev during the trial. And an additional limitation was the much smaller number of patients available for analysis beyond Period 1. Researchers said this could have led to them underestimating the rate of FVC decline.
Despite the limitations, “these results support a benefit of [Ofev] on slowing progression of IPF beyond 52 weeks,” the researchers wrote. “No new safety signals were identified with up to 86 months of treatment,” they added.