(Reuters Health) – An experimental treatment for idiopathic pulmonary fibrosis (IPF) can stall the degradation of forced vital capacity (FVC) both in patients who are undergoing therapy and among those who are not receiving antifibrotics, according to a phase 2 test of 147 volunteers.
“In the IPF field we’ve seen a handful of failures in the last five years, so to see a trial that so convincingly meets its pre-specified endpoint is, for me as a treating clinician, very exciting,” senior author Dr. Toby Maher of the University of Southern California (USC), Los Angeles, told Reuters Health in a telephone interview. “It gives us our confidence back that we may have a treatment we can take forward into the clinic.”
The study, whose results were unveiled Sunday at the American Thoracic Society’s 2022 International Conference and published online by the New England Journal of Medicine, assessed an oral therapy designated BI 1015550, which is being developed by Boehringer Ingelheim. The company paid for the study and its statisticians analyzed the data.
The company said it expects to begin phase 3 tests later this year.
According to the new results, after 12 weeks of the oral treatment, FVC readings increased from baseline by 5.7 ml among patients who were not getting background antifibrotic therapy and by 2.7 ml for patients who were receiving nintedanib or pirfenidone.
Meanwhile, among placebo recipients, FVC declined by 81.7 ml and 59.2 ml, respectively, according to a Bayesian analysis of the results.
“The stability we saw across both groups of patients for the full 12 weeks of the study was a very good surprise,” said Dr. Maher, director of interstitial lung disease as USC’s Keck School of Medicine.
The credible intervals among volunteers who were taking an antifibrotic during the experiment showed a 17.9 ml overlap, indicating that the benefit in that group might be due to chance.
There was no statistical overlap among the 73 patients who were not using antifibrotics, but the volunteers in that group tended to have better lung function to begin with. Their median FVCs at baseline were 80.4% of predicted value among BI 1015550 recipients and 82.1% of predicted value for placebo patients. The respective FVC baseline levels among those getting antifibrotics were 75.8% and 71.8%.
In addition, the patients who received background treatment tended to have been sicker longer – an average of 4.4 years versus 2.5 years in the group that did not receive background antifibrotics.
Although this trial was only 12 weeks long, there was no indication that the effect of the treatment was fading toward the end, Dr. Maher said, but “that’s a very important question the phase 3 trial will answer.”
The company announced February 24 that BI 1015550, a phosphodiesterase 4B inhibitor, had been designated as a breakthrough therapy by the U.S. Food and Drug Administration.
All the side effects that led to a discontinuation of the drug were seen in the people taking BI 1015550. Ten were taking other antifibrotic therapies and three were not.
“The most common adverse events were gastrointestinal disorders; such events led to treatment discontinuation in 5 patients,” the researchers said.
Diarrhea was the most significant problem, seen in 24% of BI 1015550 recipients versus 12% in the placebo group.
But there were no severe episodes, Dr. Maher said. “It’s more like a change in bowel habits. We can probably manage it with lifestyle changes, anti-diarrhea medicine or treatment holidays.”
There were two adverse events leading to death. Both were among BI 1015550 recipients. One of the two died from COVID-19-related pneumonia. The other was from suspected vasculitis and IPF exacerbation. Vasculitis is a side effect that can appear when IPF is treated with phosphodiesterase 4 inhibitors.
The study was done at 90 sites in 22 countries.
SOURCE: https://bit.ly/3NdkCRl The New England Journal of Medicine, online May 15, 2022.
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