High-dose bexotegrast continues to be safe, effective in INTEGRIS-IPF
BEACON-IPF Phase 2b trial to start later this year, enroll up to 270 patients
A high dose of bexotegrast, an oral treatment being developed by Pliant Therapeutics, continues to be well-tolerated for up to about nine months, with no serious side effects in people with idiopathic pulmonary fibrosis (IPF), according to long-term data from a Phase 2a trial.
Six-month data from the study, called INTEGRIS-IPF (NCT04396756), also revealed that the high dose of 320 mg per day of bexotegrast, in combination with standard of care, continued to help prevent lung function decline and to ease symptoms of cough.
This is in line with previous three-month data from the trial, which is testing the effects of once-daily bexotegrast at doses of 40, 80, 160, or 320 mg versus a placebo in 119 people with IPF for up to 48 weeks, or nearly one year.
“The INTEGRIS-IPF data provides us with confidence as we move into late-stage development,” Éric Lefebvre, MD, Pliant’s chief medical officer, said in a company press release. “I would like to thank the patients, caregivers, investigators and clinical trial staff for their participation in the INTEGRIS-IPF study.”
“We are excited to now turn our attention to initiating BEACON-IPF,” Lefebvre said.
BEACON-IPF Phase 2b study to enroll up to 270 people with IPF
BEACON-IPF is a one-year Phase 2b study that’s planned to start later this year. It’s expected to enroll up to 270 people with IPF who’ll receive 160 or 320 mg of bexotegrast, or a placebo.
IPF occurs when scar tissue forms in the lungs, which makes breathing harder. The reason this scarring happens is unknown. Over time, scarring (fibrosis) can worsen, making it more difficult for patients to go about daily activities like getting dressed or moving around.
Bexotegrast, formerly known as PLN-74809, is a small molecule designed to block alpha v beta 6 and alpha v beta 1, two proteins that are abundant in the lungs of people with IPF, where they contribute to fibrosis. By blocking these proteins, bexotegrast is expected to slow or halt fibrosis.
INTEGRIS-IPF has four parts, each testing different doses of bexotegrast for different lengths of time. In the last of the four parts, 21 patients were assigned to 320 mg of bexotegrast and eight were given a placebo for a minimum of 24 weeks and for up to 48 weeks.
About 80% of these patients were on standard of care with either Ofev (nintedanib) or Esbriet (pirfenidone), two approved medications for IPF.
This part of the study had two main goals, or endpoints. The first was to see if bexotegrast was safe to use. Forty-week data showed the high-dose of bexotegrast was well-tolerated, with no serious side effects reported.
Some mild or moderate side effects were reported, and four patients experienced diarrhea related to the use of bexotegrast. None of the patients stopped taking bexotegrast because of any side effects after the first 12 weeks of treatment.
The INTEGRIS-IPF data provides us with confidence as we move into late-stage development.
Half of bexotegrast-treated patients saw increase in FVC at week 24
The second endpoint was to evaluate the pharmacokinetics of bexotegrast, which refers to how the small molecule moves into, through, and out of the body. The high dose of 320 mg caused the levels of the medication to rise in the blood compared with lower doses of bexotegrast.
There were also some other goals, called exploratory efficacy endpoints. One of them was to see if bexotegrast improved forced vital capacity (FVC), a measure of lung function that usually decreases over time in people with IPF.
At week 24, half (50%) of bexotegrast-treated patients experienced an increase in FVC from the start of the study (baseline), while none in the placebo group did.
Moreover, most (89%) patients who had an increase in FVC from baseline to week 12 were able to maintain that increase up to week 24, meaning that their lung function did not decline as much as would be expected.
“These data build on our previously reported results and highlight a favorable long-term safety profile and provide further evidence of a durable improvement in FVC, the registrational endpoint in IPF,” Lefebvre said.
Mean change in Quantitative Lung Fibrosis, a measure of the extent of fibrosis based on lung CT scans, was below the minimally clinically important difference of 2% in bexotegrast-treated patients.
Conversely, in the placebo group, the mean change from baseline exceeded this threshold at weeks 12 and 24. Moreover, at week 24, bexotegrast-treated patients were more than twice as likely to show stable or improved Quantitative Lung Fibrosis compared with the placebo group.
Bexotegrast also helped ease cough severity as measured by a visual analog scale. Treated patients experienced a reduction of 2.9 and 1.9 points in cough severity at weeks 12 and 24, respectively. In turn, those in the placebo group reported an increase of 8.9 and 16.8 points.
“I am encouraged by the evidence of bexotegrast’s favorable impact on cough severity, a debilitating symptom in IPF patients,” said Lisa H. Lancaster, MD, the study’s principal investigator, and a professor of medicine at Vanderbilt University Medical Center in Nashville.
Together, these “data provide strong support to advance bexotegrast into late-stage development,” according to a presentation the company webcasted May 1 on its website.