Pliant Therapeutics accelerates development of bexotegrast for IPF

Oral treatment, which appears to help lung function, is moving into Phase 2b/3

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by Steve Bryson, PhD |

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Pliant Therapeutics’ Phase 2b BEACON-IPF trial testing bexotegrast, an investigational oral treatment, in people with idiopathic pulmonary fibrosis (IPF) is now a pivotal, adaptive Phase 2b/3 trial.

Accepted by European Union and global health authorities, the implementation of the adaptive design is expected to markedly shorten the therapy’s late-stage development compared with a traditional Phase 3 trial. An adaptive study design allows modifications to the trial and/or statistical procedures to be made after its start, while a pivotal trial is a study that’s specifically designed to demonstrate the safety and efficacy of a new therapy to support its marketing approval.

“The implementation of BEACON-IPF as an accelerated pivotal, adaptive Phase 2b/3 trial design is another example of our efficient approach to drug development,” Bernard Coulie, MD, PhD, president and CEO of Pliant, said in a company press release. “With this trial design, we could shorten the time to Phase 3 data meaningfully.”

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In 2023, Pliant launched the BEACON-IPF (NCT06097260) study as a Phase 2b trial with the goal of recruiting about 270 IPF patients, ages 40 and older, at clinical sites across the globe. Recruitment has begun at some sites, while in others it is expected to open soon.

Eligible participants will be randomly assigned to receive 160 or 320 mg of bexotegrast or a placebo, every day for 52 weeks, or about one year. The study’s primary goal is to assess changes in lung function through alterations in forced vital capacity (FVC) — the total amount of air exhaled after a deep breath.

Secondary outcomes include assessing the time to disease progression, defined as an absolute decrease in FVC of 10% or more, a lung-related hospitalization, or death by any cause occurring over the course of one year. In addition to safety and tolerability, a change in absolute FVC, and in the scores of the patient-reported Living with Pulmonary Fibrosis questionnaire at 52 weeks will also be evaluated.

With the new adaptive design, recruitment in the Phase 3 component of BEACON-IPF will begin after Phase 2b enrollment is complete. This adaptation will increase the statistical power of the Phase 2b trial by expanding the study population by 90 patients.

Now, both Phase 2b and Phase 3 components of BEACON-IPF can be used to support the therapy’s marketing authorization with minimal impact on timelines, according to Pliant.

Pulmonary fibrosis is a disease of the respiratory system marked by scarring, or fibrosis, in the lungs, which makes it harder for patients to breathe. In IPF, the specific underlying cause of the fibrosis is unknown.

Bexotegrast in clinical trials

Bexotegrast, formerly known as PLN-74809, is an orally available small molecule that suppresses the action of two proteins, called alpha v beta 6 and alpha v beta 1. Both proteins are found at high levels in the lungs of people with IPF and are thought to contribute to fibrosis. Blocking these proteins is expected to slow or halt fibrosis.

Early Phase 1 clinical trials showed the therapy was generally well-tolerated and led to promising anti-fibrotic effects in healthy volunteers.

Bexotegrast’s efficacy was also supported by positive findings from INTEGRIS-IPF (NCT04396756), a Phase 2a study that evaluated the effects of bexotegrast when given at doses ranging from 40 to 320 mg versus a placebo in 119 IPF patients, over the course of 48 weeks.

After three months of treatment, patients given the 320 mg dose of bexotegrast were already showing improvements in lung function and slower progression compared with the placebo group. Levels of disease-related biomarkers were also reduced. Six-month data continued to support the benefits of the high dose, which was well tolerated for up to nine months.

Pliant is also testing bexotegrast in a chronic liver disease called primary sclerosing cholangitis (PSC). This condition is characterized by inflammation and fibrosis of the bile ducts — the tubes that carry bile, a digestive fluid, from the liver to the intestines. Three-month interim data from a Phase 2a trial showed the therapy eased itching, improved liver function, and lessened fibrosis.

For both IPF and PSC, bexotegrast received fast-track designation and orphan drug status in the U.S., as well as orphan drug status in Europe. These designations aim to accelerate and support the development and regulatory review of therapies for serious diseases for which there is a high unmet need.