Bexotegrast safe, well tolerated in IPF for 12 weeks

Key takeaways:

• Around 17% of patients receiving bexotegrast reported mild to moderate diarrhea.
• Baseline FVC decreased less among those receiving bexotegrast vs. placebo when measured at week 12.

Among patients with idiopathic pulmonary fibrosis, 12-week bexotegrast was deemed well tolerated and may have an antifibrotic effect, according to results published in American Journal of Respiratory and Critical Care Medicine.

“The current study did not identify any safety concerns for bexotegrast and confirms the positive safety profile identified in the 11 completed phase 1 studies,” Lisa Lancaster, MD, professor of medicine in the division of allergy, pulmonary and critical care medicine at Vanderbilt University Medical Center, and colleagues wrote.

In the multicenter, randomized, phase 2a INTEGRIS-IPF trial, Lancaster and colleagues assessed 119 patients with IPF with or without pirfenidone or nintedanib background therapy to analyze the safety profile of four doses of oral, once-daily 12-week bexotegrast (PLN-74809; Pliant Therapeutics) vs. placebo.

Assessed doses of bexotegrast included 40 mg (n = 22; mean age, 69.2 years; 81.8% men), 80 mg (n = 23; mean age, 74.2 years; 82.6% men), 160 mg (n = 22; mean age, 71.5 years; 72.7% men) and 320 mg (n = 22; mean age, 70.5 years; 95.5% men). The remaining 31 patients (mean age, 72.1 years; 87.1% men) received placebo.

Within the total cohort, most patients (approximately 80%) were on background therapy.

Researchers had 12-week data for 92% of patients, and a greater proportion of patients receiving placebo vs. bexotegrast reported discontinuation before week 12 (12.9%; n = 4 vs. 5.7%; n = 5). In the bexotegrast group, mild diarrhea was behind two of five discontinuations.

After adding all the treatment-emergent adverse events of the bexotegrast groups together, researchers observed a comparable proportion of events between patients receiving bexotegrast and patients receiving placebo (69.7% vs. 67.7%).

Patients in the bexotegrast groups and the placebo group frequently reported diarrhea (16.9%; n = 15 vs. 9.7%; n = 3), which was primarily mild to moderate in severity in the bexotegrast group, according to researchers.

Notably, simultaneous nintedanib use was a common characteristic among those who experienced diarrhea in the bexotegrast group (86.7%; n = 13) and the placebo group (33.3%; n = 1).

Researchers pulled out treatment-emergent adverse events of IPF/pulmonary fibrosis and found a greater proportion of patients receiving placebo vs. bexotegrast reporting these type of events (9.7% vs. 2.3%).

“Overall, bexotegrast was well tolerated when used in combination with IPF background therapy or used as monotherapy,” Lancaster and colleagues wrote.

In addition to safety, researchers looked at how bexotegrast impacted lung function, quantitative lung fibrosis and fibrosis-related biomarkers compared with placebo.

Regardless of background therapy, baseline FVC decreased less among those receiving bexotegrast (pooled doses) vs. placebo when measured at week 12 (–3.6 mL vs. –110.5 mL). More specifically, this change significantly differed between the placebo group and 80 mg bexotegrast group by 136.1 mL (P = .0094), as well as between the placebo group and the 320 mg group by 139.9 mL (P = .0124).

In terms of quantitative lung fibrosis extent, the mean percent change over 12 weeks depended on the bexotegrast dose. Patients receiving the two higher doses of bexotegrast had “no or limited progression,” according to researchers.

Lastly, receipt of bexotegrast compared with placebo lowered two fibrosis-related biomarkers from baseline to week 12: plasma integrin beta 6 and serum type III collagen synthesis neoepitope.

“These results support the need for further studies of bexotegrast for the treatment of IPF,” Lancaster and colleagues wrote.