Atyr plans new global clinical trial of efzofitimod in pulmonary sarcoidosis
Company recently discussed potential path to drug's approval with the FDA
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Atyr Pharma plans to launch a new global clinical trial to test its investigational therapy, efzofitimod, in people with pulmonary sarcoidosis and a restrictive profile, in which the lungs cannot fully expand.
The decision follows a type C meeting with the U.S. Food and Drug Administration (FDA) to discuss results from the previous Phase 3 EFZO-FIT clinical trial (NCT05415137) and the potential path for efzofitimod’s approval.
EFZO-FIT failed to meet its main goal of showing efzofitimod significantly reduced the need for standard corticosteroids compared with a placebo in pulmonary sarcoidosis patients. However, the experimental therapy was associated with benefits, including a higher likelihood of discontinuing corticosteroids, improvements in quality of life, and reduced fatigue.
“We are pleased with the feedback we received from the FDA on the path forward for efzofitimod in pulmonary sarcoidosis and the productive discussion we had regarding the most clinically relevant [outcomes] for this disease,” Sanjay S. Shukla, MD, Atyr Pharma’s president and CEO, said in a company press release. “To align with this feedback, we will prioritize FVC [forced vital capacity] as the primary [outcome] in our next study.”
Based on the FDA’s feedback, the new global Phase 3 clinical trial, dubbed C-006, will focus on changes in lung function, specifically FVC (forced vital capacity), which measures the maximum volume of air forcefully exhaled after a deep breath. Changes in the King’s Sarcoidosis Questionnaire (KSQ)-Lung score, a standardized measure of how lung symptoms affect patients’ daily lives, will be a key secondary outcome.
The FDA’s feedback and planned design for the upcoming Phase 3 trial were discussed last week in a company webcast. Atyr expects to file for the trial’s clearance in June.
Efzofitimod aims to reduce inflammation, formation of granulomas
Pulmonary sarcoidosis is caused by an overactive immune response that leads to the formation of small clusters of immune cells, called granulomas, in the lungs. This leads to inflammation and scarring (fibrosis), which can cause symptoms such as shortness of breath and a persistent cough.
Oral corticosteroids, which suppress inflammation and immune responses, are the first-line treatment for pulmonary sarcoidosis. However, their long-term use, or use at high doses, can cause serious side effects.
Efzofitimod is designed to help reduce inflammation and granuloma formation, potentially improving lung function and easing symptoms in people with pulmonary sarcoidosis.
Administered directly into the bloodstream, the treatment works by modulating the activity of NRP2, a receptor protein found on the surface of certain immune cells that drive inflammation and granuloma formation.
Previous trials showed treatment led to improvements
In a previous Phase 1b/2a trial (NCT03824392), efzofitimod reduced symptoms, improved lung function, and reduced the need for corticosteroids in patients with pulmonary sarcoidosis. The two highest doses, 3 mg/kg and 5 mg/kg, reduced relapse rates after corticosteroid taper.
In the global EFZO-FIT study, 268 adults with pulmonary sarcoidosis received efzofitimod at a dose of 3 mg/kg or 5 mg/kg, or a placebo, every four weeks. While top-line results showed that the mean daily corticosteroid dose was lower in the efzofitimod group than in the placebo group, the difference was not statistically significant, meaning it could be due to chance.
Still, additional analyses demonstrated that efzofitimod led to clinically meaningful improvements in FVC relative to the placebo among the 44 participants with restrictive lung disease, defined as an FVC between 50% and 80% of the predicted value. These patients also experienced positive trends in patient-reported outcomes, including the KSQ-Lung score.
“We believe that focusing on these two key [outcomes] that are viewed as direct measures of function and feel by the FDA and doing so in a defined patient population where we have a demonstrated benefit for efzofitimod is the appropriate strategy for the next step in evaluating efzofitimod as a potential new treatment for patients with pulmonary sarcoidosis,” Shukla said.
The new Phase 3 trial is expected to enroll up to 372 people with moderate-to-severe pulmonary sarcoidosis and a restrictive profile. Eligible participants may continue on stable treatment with oral corticosteroids (up to 5 mg daily) and/or immunosuppressive agents.
Participants will be randomly assigned to receive either 5 mg/kg efzofitimod or a placebo, every three weeks instead of the previously tested once-a-month regimen, for 48 weeks (nearly one year). The FDA agreed with the most frequent treatment regimen and associated risk mitigation strategies proposed by Atyr to assess potential safety issues.
“Considering the consistent safety profile we have seen for efzofitimod in trials to date, we believe this strategy to increase drug exposure, coupled with additional risk mitigation strategies and safety surveillance, may enhance the effects of efzofitimod without incurring additional safety concerns,” Shukla said.
