Final trial data show pulmonary sarcoidosis drug helps patients
Despite failing to meet main goal, infusion therapy improved outcomes
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Treatment with the investigational drug efzofitimod — given by infusion once every four weeks — significantly improved general health and lung-related quality of life in adults with pulmonary sarcoidosis while also significantly easing fatigue and numerically reducing the use of oral corticosteroids.
Lung function was also preserved among patients receiving efzofitimod, which was generally well tolerated.
That’s according to the final data from a global late-stage clinical trial that tested the therapy candidate against a placebo for nearly one year in more than 250 people with pulmonary sarcoidosis, a rare inflammatory disease affecting the lungs. Developer Atyr Pharma says these data, from a Phase 3 study dubbed EFZO-FIT (NCT05415137), show that while the trial failed to meet its main goal, the therapy still demonstrated significant benefits on patient-reported measures.
The California-based biotech company reported last year that efzofitimod did not significantly lessen patients’ need for corticosteroids — a cornerstone treatment — compared with the placebo.
These final data were detailed in a study titled “Efzofitimod versus placebo in patients with pulmonary sarcoidosis (EFZO-FIT): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial,” published in the journal The Lancet Respiratory Medicine.
“Publication of the EFZO-FIT results strengthens the evidence supporting efzofitimod,” Sanjay S. Shukla, MD, president and CEO of Atyr, said in a company press release announcing the publication.
“The improvements across multiple [patient-reported outcomes], together with preserved lung function and a favorable safety profile, reinforce our confidence in efzofitimod’s potential and provide a strong foundation for its continued development in pulmonary sarcoidosis,” Shukla said.
Atyr is planning to launch another global Phase 3 trial to test efzofitimod in pulmonary sarcoidosis patients with moderate to severe disease and restrictive lung disease, which impairs the lungs’ ability to fully expand. The main goal of that study, which is anticipated to recruit more than 350 patients, will be to assess if the therapy is superior to a placebo in improving lung function.
Pulmonary sarcoidosis is marked by clusters of immune cells, called granulomas, that build up in the lungs, typically causing inflammation and scarring, known as fibrosis. That accumulation can lead to coughing, shortness of breath, and reduced lung function.
For most patients, treatment starts with corticosteroids, which help control inflammation by broadly suppressing immune activity. But long-term use of these drugs can cause serious side effects.
As such, “there is an urgent need for safe, effective and tolerable treatments for [pulmonary] sarcoidosis that have a positive impact on patient quality of life,” said Daniel Culver, MD, chair of the division of pulmonary medicine at the Cleveland Clinic and the study’s first author.
Despite less steroid use, trial did not meet main endpoint
Given by infusion directly into the bloodstream, efzofitimod was designed to reduce inflammation without broadly suppressing the immune system.
It works by selectively regulating the activity of NRP2, a receptor protein found on the surface of certain immune cells involved in inflammation and granuloma formation. It’s expected to reduce lung inflammation and fibrosis and improve lung function in people with pulmonary sarcoidosis.
EFZO-FIT tested two doses of efzofitimod — 3 and 5 mg/kg — against a placebo, given approximately monthly for 48 weeks, or just short of one year, in people ages 18 to 75 with pulmonary sarcoidosis. Starting two weeks after the first infusion, all participants underwent a 12-week plan to gradually reduce their oral corticosteroid doses.
Data from 264 participants were used in the final analyses.
The trial’s main goal was to determine whether efzofitimod could reduce mean daily oral corticosteroid use compared with the placebo. Among the overall patient population, the mean dose dropped from 10.7 mg at the study’s start to 2.9 mg after 48 weeks, the data showed.
Despite this substantial drop, however, neither efzofitimod dose led to a significantly greater reduction than the placebo — meaning the trial failed to meet its main goal.
The large drop in corticosteroid use observed also in the placebo group “might in part be due to the rigid [corticosteroid] reduction protocol,” the researchers wrote. It also “suggests that some patients might be over-treated in current practice and highlights the need for more precise tools to assess treatment effectiveness.”
Potential benefits still seen with higher efzofitimod dose
Still, other measures pointed to potential benefits with the higher efzofitimod dose.
Compared with the placebo, 5 mg/kg efzofitimod was associated with significantly greater improvements in lung-related quality of life, assessed using scores on the King’s Sarcoidosis Questionnaire (KSQ)-Lung. Significant improvements were also observed in general health, as measured by the KSQ-General Health score, after 48 weeks. The high-dose group also showed significantly greater reductions in fatigue, measured by the Fatigue Assessment Scale.
“Improvements occurred early and were sustained” for all measures, the researchers wrote.
Additionally, participants treated with the high dose were significantly more likely to stop taking corticosteroids completely while also reporting KSQ-Lung score improvements (30% vs. 14%), per the data.
Lung function, measured by forced vital capacity, was generally stable, without significant differences between groups.
Improvements [with efzofitimod] occurred early and were sustained [for all measures].
The researchers noted that efzofitimod was generally well tolerated, with most adverse events being mild or moderate in severity. Headache, sinusitis, and wheezing were more common in efzofitimod-treated participants.
Two patients receiving the lower dose died during the study, one from respiratory failure and another from complications of a pre-existing hernia. Neither death was considered related to treatment.
“The findings … represent an important advancement in our understanding of how patients can be appropriately managed with [corticosteroids] and is likely to lead to a paradigm shift in the way that we treat sarcoidosis patients and evaluate new therapies for this patient population in the future,” Culver said.
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