The idiopathic pulmonary fibrosis (IPF) treatment candidate BBT-877 is safe and well-tolerated in healthy volunteers, and markedly reduced the plasma levels of a lipid molecule involved in inflammation and fibrosis, according to results of a Phase 1 clinical trial.
The research, “BBT-877, a potent Autotaxin Inhibitor in Clinical Development to Treat Idiopathic Pulmonary Fibrosis,” was presented at the European Respiratory Society International Congress 2019, held in Madrid, Spain, Sept. 28–Oct. 2.
BBT-877 is an oral small molecule inhibitor of autotaxin (ATX). This enzyme is found at increased levels in the lungs of IPF patients, and plays a role in the production of lysophosphatidic acid (LPA), a lipid (fat) involved in fibrosis, or scarring. As such, by inhibiting ATX, BBT-877 may slow IPF progression.
The Phase 1 study (NCT03830125), sponsored by Bridge Biotherapeutics, the developer of BBT-877, assessed the pharmacokinetics (the absorption, distribution, metabolism, and excretion in the body), the pharmacodynamics (how the body responds to a therapy), and safety of BBT-877 in 80 healthy volunteers.
After a single-ascending dose (SAD) part testing five different oral doses (50 to 800 mg), the multiple-ascending dose (MAD) portion assessed 200 to 800 mg given once per day in three groups, and 100 to 200 mg twice daily in two groups over two weeks.
In both parts of the trial, the plasma level of BBT-877, its maximum concentration, and a plot of its concentration versus time after dosage — called “area under the curve” — all increased in a dose-proportional manner.
Higher doses also correlated with greater systemic exposure to BBT-877. The potential therapy’s half-life (the time until its concentration is reduced by half) was approximately 12 hours across all dose levels.
The data further showed that BBT-877 suppresses LPA production, also with greater effects at higher doses. Plasma LPA levels were reduced by at least 80% for 24 hours with 400 mg or higher doses of BBT-877 in the SAD portion. In the MAD part, both 100 mg twice daily and 200 mg twice daily dosages led to a maximum of 90% of LPA suppression at a steady state.
The effective dose of BBT-877 in patients is predicted within the 100-200 mg twice daily range.
As in previously reported results of the SAD portion, all BBT-877 doses were well-tolerated, and with no serious adverse side effects. Safety assessments did not lead to clinically-related findings in electrocardiogram, vital signs, biochemical and blood cells’ tests, and urine analysis.
Last January, the U.S. Food and Drug Administration granted orphan drug designation to the experimental therapy based on data obtained from a mouse study suggesting that BBT-877 may ease lung fibrosis.
“In addition to the non-clinical data proving the strong, competitive efficacy of BBT-877 in mouse models, this encouraging first-in-human study results demonstrated that BBT-877 is a well-tolerated drug candidate with excellent pharmacokinetic and pharmacodynamic profiles,” Gwang-hee Lee, PhD, Bridge’s vice president, head of translational research at Bridge, said in a press release.
In July, Boehringer Ingelheim obtained a license from Bridge Biotherapeutics to develop BBT-877 beyond Phase 1, adding to the company’s portfolio of treatment candidates for fibrosing interstitial lung diseases.
“We look forward to [providing] patients with IPF with new treatment option as early as possible by continuing to advance this encouraging development program with Boehringer Ingelheim,” Lee said.
Kay Tetzlaff, MD, Boehringer Ingelheim’s vice president and medical head of therapeutic area inflammation, added: “We are delighted about the promising results demonstrated in Phase 1 clinical studies conducted by our partner Bridge Biotherapeutics for BBT-887.”
Bridge Biotherapeutics also has been conducting a toxicology study for long-term dosages, expected to be completed in early 2020. An international Phase 2 study of BBT-877 is planned to start by mid-2020.