Atyr, FDA align on efzofitimod trial analysis for pulmonary sarcoidosis
EFZO-FIT's main goal is to assess changes in mean daily oral corticosteroid dose
Atyr Pharma and the U.S. Food and Drug Administration (FDA) have aligned on the specific main outcome analysis of the ongoing Phase 3 clinical trial that’s testing the company’s investigational therapy efzofitimod in people with pulmonary sarcoidosis.
Based on FDA feedback during a recent type C meeting, the trial’s main goal of oral corticosteroid reduction will be measured as the absolute change in dosage from the study’s start to after the one-year treatment period, according to an Atyr press release that announced the update.
The study, called EFZO-FIT (NCT05415137), will continue without modifications following a fourth pre-planned independent data and safety monitoring board (DSMB) review. The previous DSMB review occurred at year’s end. DSMBs are made up of independent specialists who routinely analyze clinical trial data to ensure data integrity and patient safety. EFZO-FIT’s top-line data are expected by September.
“Leading into this pivotal readout, we are very pleased with the execution of the study to date and the continued favorable safety profile demonstrated for efzofitimod, including our most recent positive DSMB review, which recommended the study continue as designed,” Sanjay S. Shukla, MD, president and CEO of Atyr, said in the release.
“As we look to position efzofitimod as a potential chronic, maintenance therapy for patients with pulmonary sarcoidosis that can reduce or eliminate the use of oral corticosteroids, we are pleased to see no safety concerns arise as the study progresses,” Shukla said in a separate company press release.
In sarcoidosis, granulomas, or clumps of inflammatory cells, build up in various organs and tissues. In about 90% of cases, these granulomas form in the lungs, leading to inflammation and scarring (fibrosis) of lung tissue, which makes breathing difficult. Current treatment options include corticosteroids, which have anti-inflammatory and immunosuppressive properties. Their long-term use can cause serious side effects, however.
Efzofitimod’s effect on symptoms
Formerly ATYR1923, efzofitimod is a first-in-class immunomodulator that’s designed to selectively regulate the activity of neuropilin-2 (NRP2), a receptor protein on the surface of certain immune cells that drive inflammation and granuloma formation.
Administered directly into the bloodstream, efzofitimod should restore immune system balance and reduce inflammation without compromising healthy immune responses. In this way, the candidate therapy aims to reduce fibrosis and improve lung function in pulmonary sarcoidosis and other interstitial lung diseases (ILDs), a group of diseases marked by scarring.
Preclinical data supporting efzofitimod’s mechanism of action and therapeutic benefits were recently published in Science Translational Medicine in a study titled “A human histidyl-tRNA synthetase splice variant therapeutic targets NRP2 to resolve lung inflammation and fibrosis.”
Exposure to efzofitimod blocked the production of pro-inflammatory molecules and suppressed inflammatory pathways in lab-grown human macrophages, a type of immune cell that contributes to granulomas.
In animal models of lung injury and ILD, efzofitimod reduced lung inflammation, immune cell infiltration, and fibrosis. In people with sarcoidosis, efzofitimod reduced inflammatory pathways in circulating immune cells and stabilized inflammatory biomarkers in the blood after steroid tapering.
“We are pleased to publish this extensive manuscript detailing the preclinical data supporting the development of efzofitimod, which includes all of the data generated for this novel drug candidate from concept to clinic,” Leslie A. Nangle, PhD, Atyr’s vice president of research, said in a separate company press release. “This peer-reviewed publication in a highly regarded journal … validates the immunomodulatory activity and … mechanism of efzofitimod in reducing inflammation and fibrosis.”
A previous Phase 1b/2a trial (NCT03824392) showed efzofitimod eased symptoms, improved lung function, and lowered the need for corticosteroids. According to a follow-up analysis, the two highest doses of efzofitimod tested (3 and 5 mg/kg) reduced relapse rates or the need to increase the corticosteroid dose.
The ongoing EFZO-FIT trial, which completed enrollment in mid-2024, is evaluating the safety and efficacy of the higher efzofitimod doses against a placebo in 268 adults with pulmonary sarcoidosis. The participants are receiving efzofitimod or the placebo for up to 48 weeks and all can continue their corticosteroid treatment, but will undergo a forced dose reduction during the trial.
The study’s main goal is to assess changes in mean daily oral corticosteroid dose. Secondary goals include changes in sarcoidosis symptoms and lung function.
“Efzofitimod is poised to potentially become a safe and effective alternative to the current standard of care and improve patients’ lives,” Shukla said.
Patients who complete the study and wish to continue efzofitimod treatment may enroll in an individual patient expanded access program. These types of programs let patients access experimental treatments outside of clinical trials when no other options are available.
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