FDA, developer align on protocols for trial of pulmonary sarcoidosis drug
Atyr now gearing up for global study expected to enroll over 350 patients
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Over the coming months, Atyr Pharma will be working toward the launch of a global clinical trial testing its therapy candidate efzofitimod in people with moderate to severe pulmonary sarcoidosis and restrictive lung disease, which together make it difficult for the lungs to fully expand, hampering breathing.
The update comes after Atyr reached an agreement with the U.S. Food and Drug Administration (FDA) on the trial’s final design. The upcoming Phase 3 study, whose plans were initially announced in May, is expected to enroll about 372 participants at sites worldwide. Its main goal will be to determine whether efzofitimod can improve lung function compared with a placebo.
“We received feedback earlier this week from the FDA and we are very pleased to have reached alignment on the protocol for our planned Phase 3 study of efzofitimod in pulmonary sarcoidosis,” Sanjay S. Shukla, MD, Atyr’s president and CEO, said in a company press release. “This important milestone reflects the progress of our efforts to advance efzofitimod for patients with pulmonary sarcoidosis.”
The company’s soon-to-be-initiated trial-related activities will include submissions to regulatory agencies in the U.S. and Europe seeking a go-ahead to conduct the trial on both sides of the Atlantic. Atyr noted, however, that advancing efzofitimod into trial will require additional funding. The company plans to raise money through equity or debt financing, grants, collaborations, strategic partnerships, and/or licensing agreements.
Sarcoidosis is caused by an overactive immune response that leads to the formation of clusters of immune cells, called granulomas, in tissues throughout the body. When granulomas form in the lung or lungs, the condition is called pulmonary sarcoidosis.
The resulting inflammation and scarring in the lungs can interfere with their function and cause symptoms such as shortness of breath and a persistent cough.
The first-line treatment for sarcoidosis is oral corticosteroids, which suppress the immune responses that drive inflammation and granuloma formation. However, taking these drugs for long periods or at high doses can cause serious side effects — which highlights the need for safer and more effective treatments, particularly those that are disease-modifying, per the developer.
Trial will test if efzofitimod can improve lung function
Efzofitimod, given intravenously, or as an infusion into the bloodstream, is designed to reduce inflammation and granuloma formation by modulating the activity of neuropilin-2 (NRP2), a protein found on immune cells that are involved in inflammation and the formation of granulomas. In targeting that protein, the therapy candidate is expected to ease symptoms and improve lung function in people with pulmonary sarcoidosis.
In the planned Phase 3 trial, called C-006, eligible participants will be randomly assigned to receive either 5 mg/kg of efzofitimod or a placebo by infusion once every three weeks, for a total of 17 doses.
The study is expected to last 54 weeks, or slightly longer than one year. During its course, participants will be allowed to continue on stable treatment with oral corticosteroids, at a doses of up to 5 mg daily, and/or other immunosuppressive agents.
The trial’s main goal is to assess changes at week 48, or near the one-year mark, in lung function as measured by forced vital capacity (FVC), an evaluation of how much air a person can forcefully breathe out after taking a deep breath.
A key secondary goal will assess changes in the King’s Sarcoidosis Questionnaire (KSQ)-Lung score, which captures how lung symptoms affect a person’s daily life.
Eligible patients will have pulmonary sarcoidosis and lung disease
The design of the new trial builds on findings from a previous Phase 3 study, dubbed EFZO-FIT (NCT05415137), which involved 268 adults with pulmonary sarcoidosis who received efzofitimod at a dose of 3 mg/kg or 5 mg/kg, or a placebo. Treatment was given once a month, for a total of 12 infusions.
The high dose of efzofitimod was associated with several benefits, such as significant improvements in quality of life and reductions in fatigue. However, the trial failed to meet its main goal of showing a significant reduction in daily corticosteroid use compared with the placebo at 48 weeks.
Still, additional analyses pointed to potentially greater benefits in a subgroup of participants with restrictive lung disease, defined as an FVC between 50% and 80% of the predicted value. Those treated with high-dose efzofitimod showed clinically meaningful FVC improvements and trends toward greater corticosteroid reductions relative to those on the placebo.
These efzofitimod-treated patients also showed positive trends in patient-reported outcomes, including the KSQ-Lung score and fatigue.
With limited treatment options available, particularly for patients requiring chronic therapy, we believe efzofitimod has the potential to become an important new treatment option.
Based on these findings and the FDA’s feedback, Atyr decided to focus the new study on patients with restrictive lung disease. The company now will prioritize changes in FVC as its main measure of the therapy’s effectiveness.
Earlier clinical testing had also provided evidence of potential benefit among people with pulmonary sarcoidosis. In a previous Phase 1b/2a trial (NCT03824392), efzofitimod reduced symptoms, improved lung function, and reduced corticosteroid use. The two highest doses, 3 mg/kg and 5 mg/kg, were also associated with lower relapse rates after corticosteroids were tapered.
“With limited treatment options available, particularly for patients requiring chronic therapy, we believe efzofitimod has the potential to become an important new treatment option,” Shukla said.
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