The therapy Ofev (nintedanib) was shown to slow down the progression of idiopathic pulmonary fibrosis (IPF) through 96 weeks, regardless of a patient’s lung disease severity at the beginning of the study period, a preliminary analysis of the extension INPULSIS-ON trial found.
INPULSIS-1 (NCT01335464) and INPULSIS-2 (NCT01335477) were two global Phase 3 clinical trials designed to evaluate Ofev’s effectiveness and safety in the treatment of IPF.
Patients who completed a 52-week treatment period and a four-week follow-up period in the INPULSIS trials were invited to continue to receive Ofev in an open-label extension trial — INPULSIS-ON (NCT01619085) — to assess the long-term safety and tolerability of Ofev. The extension trial included 734 patients and is still ongoing.
Ofev manufacturer Boehringer Ingelheim recently presented preliminary results from the extension study at the 2017 CHEST Annual Meeting, along with a separate analysis of data from the IPF-PRO Registry (NCT01915511), which showed trial enrollees were representative of IPF patients in a real-world setting.
The U.S. Food and Drug Administration (FDA) approved Ofev for the treatment of IPF in October 2014. It is one of the first FDA-approved treatments for IPF and the only kinase inhibitor available for the treatment of the disease.
The results presented at CHEST 2017 show that Ofev slows the annual rate of decline in lung function, as measured by forced vital capacity (FVC), over 96 weeks regardless of the severity of patients’ lung conditions at the start of the study. FVC measures the amount of air that can be forcibly exhaled after a breath.
Specifically, the adjusted annual rates of decline in lung function over 96 weeks were consistent among patients with FVC equal or inferior to both 70% and 90% predicted at baseline, and with FVC superior to both 70% and 90%.
Additionally, the adjusted annual rate of lung function decline in all participants in the INPULSIS-ON extension study at 96 weeks was comparable to the rate observed at 52 weeks in the IMPULSIS trials.
“Baseline lung function and changes in FVC over time are both important predictors of long-term outcomes in IPF, so it is critical to maintain lung function across disease severities,” said Mitchell Kaye, MD, president of the Minnesota Lung Center/Minnesota Sleep Institute, in Minneapolis, in a press release.
“These new results provide further supportive evidence for the long-term efficacy of Ofev, suggesting the value of initiating IPF treatment irrespective of a person’s disease severity at diagnosis,” he added.
A second abstract presented at CHEST 2017 presented findings from the IPF-PRO Registry, which concluded that the characteristics of patients with IPF who participated in these clinical trials were comparable to patients in the real-world, according to data from 18 pulmonary care sites.
“Boehringer Ingelheim is continually focused on better understanding IPF and identifying prescribing patterns and treatment outcomes in real-world settings,” said Thomas Leonard, PhD, executive director of clinical development and medical affairs, specialty care, at Boehringer Ingelheim.
“The knowledge we are unlocking through the ongoing IPF-PRO Registry underscores this commitment and will help us improve the care of those living with this disease,” he added.
ProMetic Life Sciences recently announced that the U.S. Food and Drug Administration (FDA) agreed with the design of the first Phase 2/3 clinical trials evaluating PBI-4050 for idiopathic pulmonary fibrosis (IPF) treatment.
PBI-4050 is an oral drug designed to treat fibrosis, a condition characterized by the replacement of normal tissue by fibrotic scar tissue.
The planned Phase 2/3 clinical trials for IPF are based on positive Phase 2 trial results of the drug’s effectiveness and tolerability as a monotherapy and in combination with Ofev (nintedanib) or Esbriet (pirfenidone).
This open-label, single-arm, Phase 2 clinical trial (NCT02538536) enrolled 40 IPF patients and assessed the effectiveness, safety, and tolerability of PBI-4050 (800 mg daily, oral administration) on lung function and disease progression.
Results reported in February showed that after 12 weeks of treatment, the forced vital capacity (FVC, a measure of lung function) remained stable in patients treated with PBI-4050 alone (nine patients), and in patients treated with PBI-4050 in combination with Ofev (15 patients). In patients treated with PBI-4050 in combination with Esbriet (16 patients), FVC declined significantly.
The plasma concentration of PBI-4050 was sub-therapeutic at 50 percent of the expected level in patients that received the PBI-4050 in combination with Esbriet, indicating negative drug-drug interaction.
“This early evidence of efficacy observed with PBI-4050 alone or in combination with nintedanib [Ofev] points toward very promising treatment options that will be further tested in two separate Phase 2/3 clinical trials. We are very pleased that the FDA concurs with our decision to exclude a combined pirfenidone [Esbriet] and PBI-4050 treatment arm in the upcoming phase 2/3 add-on study,” John Moran, chief medical officer of ProMetic said in a press release.
In the new study, planned to begin in a few months, IPF patients currently treated with Ofev will be randomly assigned to additional treatment with either PBI-4050 or a placebo.
The company is also considering conducting another Phase 2/3 placebo-controlled clinical trial with PBI-4050 in IPF patients who did not tolerate Ofev or Esbriet.
“To date, PBI-4050 has presented a remarkable safety and tolerability profile throughout all clinical trials,” said Pierre Laurin, president and CEO of ProMetic. “We are also very pleased that our Phase 2 open label study in IPF patients has served the very important strategic purpose of allowing us to optimize the design of our pivotal clinical program for this devastating medical condition.”