PBI-4050 slowed or stopped declines in lung function in patients with IPF.
The novel agent PBI-4050 slowed or stopped declines in lung function when administered as a single-agent or in combination with nintedanib for patients with idiopathic pulmonary fibrosis (IPF), according to phase 2 findings presented at the 2017 ATS International Conference.1
In the 12-week trial, forced vital capacity (FVC) declined by just 1.1% with single-agent PBI-4050 (95% CI, -4.0 to 1.8). When combined with nintedanib, FVC improved by 0.1% (95% CI, -1.9 to 2.0). PBI-4050 was also combined with pirfenidone but did not render a benefit. In this group, FVC declined by 2.7% (95% CI, -4.8 to -0.6).
"PBI-4050 was well tolerated and demonstrated a good safety profile in IPF subjects when given alone or in combination with nintedanib/pirfenidone," said Joseph Parker, MD, senior director, Clinical Development at ProMetic BioTherapeutics, the developer of the agent. "PBI-4050 alone and in combination with nintedanib demonstrated promise in slowing or stopping the decline in lung function."
The study randomized 40 patients with IPF to receive PBI-4050 alone (n = 9) or in combination with either nintedanib (n = 16) or pirfenidone (n = 16). Patient demographics were well balanced across groups, with a mean age of 68.6 years. Most patients were male (75%) and 73.9% were predicted to have a normal FVC. Diffusing capacity of the lungs for carbon monoxide (DLCO) was predicted to be normal for 48.9% of patients.
In the single-agent arm, FVC was reduced by 12 mL (95% CI, -102 to 77). In combination with nintedanib, FVC increased by 2 mL (95% CI, -61 to 64). Patients who received PBI-4050 plus pirfenidone had a 102 mL decline in FVC (95% CI, -172 to -32).
Pharmacokinetic (PK) profiles for PBI-4050 were similar between healthy volunteers and those with IPF as a single agent and in combination with nintedanib. However, PBI-4050's PK was significantly reduced when combined with pirfenidone, suggesting a drug-drug interaction. Given these findings, future studies will omit the pirfenidone arm.
Although data from the phase 2 study were from just 12 weeks of follow-up, Parker noted that changes in FVC in the PBI-4050 plus nintedanib arm seemed superior to nintedanib alone from other phase 3 studies.
In the phase 3 INPULSIS-1 trial,2 FVC reduced by 114.7 mL with single-agent nintedanib versus 239.9 mL with placebo (95% CI, 77.7-172.8; P <.001). In the INPULSIS-2 study, FVC declined by 113.6 mL with nintedanib versus 207.3 mL with placebo (95% CI, 44.8-142.7; P <.001). Together, these findings led to the FDA approval of nintedanib for IPF in 2014.
A phase 2/3 study to explore PBI-4050 with nintedanib is currently being planned by ProMetic BioTherapeutics. Additionally, a phase 2/3 study looking at single-agent PBI-4050 is planned for patients with IPF who are unable to tolerate or fail standard of care therapy.