Long-term use of Boehringer Ingelheim’s Ofev (nintedanib) prevents disease progression in patients with idiopathic pulmonary fibrosis (IPF), according to the latest results of the TOMORROW trial and its open-label extension.
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.
In the Phase 2 TOMORROW trial (NCT00514683), researchers evaluated Ofev’s safety and efficacy compared to a placebo (control) in two periods. During period 1, patients received one of four doses of the treatment or a placebo for up to 52 weeks. Patients who completed period 1 continued treatment with Ofev in period 2 — with participants unaware whether they were taking Ofev or a placebo — until the last patient had completed the 52-week, period 1.
Those who completed period 2 of the trial then had the opportunity to engage in the open-label extension trial, during which participants were aware of what they were taking, to continue or initiate Ofev treatment (NCT01170065).
Period 1 of the trial included a total of 428 patients diagnosed with IPF, of which 286 continued treatment during period 2. For the extension study, a total of 198 patients participated. Overall, the study completed a mean treatment time of 27.6 months for Ofev and 28.1 months with the placebo.
Previous results of the TOMORROW trial showed that treatment with 150 mg of Ofev (the recommended dose of Ofev in IPF) administrated twice daily was associated with a reduced respiratory function decline and lower incidence of acute exacerbations when compared to the placebo group.
Analysis of the extended data collected from the TOMORROW trial and its open-label extension demonstrated the long-term benefits of Ofev. Patients who received the drug experienced an annual rate of decline in forced vital capacity of −125.4 mL/year, compared to those in a comparator group who experienced a −189.7 mL/year rate of decline. Patients in the comparator group received placebo in period 1 of the TOMORROW trial, followed by Ofev 50 mg once daily in period 2. Additionally, they began the extension trial on the dose that they were receiving at the end of period 2, but had the option to increase their nintedanib dose to 150 mg twice daily.
Among IPF patients who received Ofev, only 12.9 percent experienced one or more acute exacerbation during the study, while in the comparator group, the incidence of exacerbations was of 25.9 percent.
Overall, treatment with Ofev was associated with a reduction of 47 percent in the risk of acute exacerbation, and a reduction of 30 percent in the risk of all-cause mortality among IPF patients. This finding is in accordance with previous analysis of pooled data from TOMORROW period 1 and the Phase 3 INPULSIS trials (NCT01335464 and NCT01335477).
The researchers concluded that “[the] results from the TOMORROW trial and its open-label extension support an effect of nintedanib [Ofev] on slowing the progression of IPF beyond 52 weeks.”
Ofev’s safety and tolerability profiles reported during TOMORROW and open-label extension trials were similar to those reported in previous studies.