aTyr Readies Phase 3 Study of Efzofitimod in Pulmonary Sarcoidosis
Expected to begin later this year, the primary goal of the study — dubbed EFZO-FIT — will be a reduction in therapeutic corticosteroids, which can result in serious side effects.
The move comes on the heels of positive feedback from the U.S. Food and Drug Administration (FDA), which reviewed data provided by the company, including those from a recently completed Phase 1b/2a clinical trial.
The agency advised aTyr to evaluate multiple doses of the investigational therapy in a longer study to establish the safest and most effective dose for chronic use.
“We are very pleased with the input we received from the FDA regarding the design of this important study of efzofitimod in pulmonary sarcoidosis patients,” Sanjay S. Shukla, MD, president and CEO of aTyr, said in a press release. “We aligned with the FDA on the prioritization of efficacy endpoints [outcomes], with a primary focus on steroid reduction, which is clinically meaningful to patients and providers.
“This late-stage study is a major milestone for aTyr and the sarcoidosis community, and we look forward to the expected initiation of the study in the third quarter of this year,” Shukla added.
In sarcoidosis, an overactive immune system leads to the formation of clumps of inflammatory cells, or granulomas, in various tissues. When granulomas occur in the lungs, the condition is known as pulmonary sarcoidosis.
Efzofitimod, previously called ATYR1923, is a first-in-class immunomodulator that suppresses immune responses in uncontrolled inflammatory diseases. The investigational therapy does so by selectively modulating neuropilin-2 (NRP2), which is a protein on immune cells that plays a role in granuloma formation in pulmonary sarcoidosis.
In the completed proof-of-concept Phase 1b/2a trial (NCT03824392), adults with pulmonary sarcoidosis received monthly intravenous (into-the-vein) infusions of the therapy.
Outcome data showed the highest dose (5 mg/kg) led to significant improvements in lung function, as well as reduced shortness of breath, cough, and fatigue, compared to a placebo. At all three doses tested, efzofitimod was well tolerated and safe.
The investigational pulmonary sarcoidosis treatment also lowered by 58% the use of corticosteroids, which are medicines often used to treat the disorder. According to the company, efzofitimod’s steroid-sparing effect was one of the reasons supporting the FDA’s favorable opinion.
The new one-year EFZO-FIT Phase 3 registrational study intends to enroll 264 patients with pulmonary sarcoidosis at multiple centers in North America, Europe, and Japan. A registrational trial is required by regulatory authorities as a prerequisite to obtain approval.
Participants will be assigned randomly to receive either 3.0 mg/kg or 5.0 mg/kg doses of efzofitimod, or placebo, administered intravenously once a month for a total of 12 doses.
In addition to reducing corticosteroid use, secondary objectives include changes in lung function and other sarcoidosis symptoms.
“This study is a major step forward in developing a new treatment for patients with sarcoidosis,” added Robert P. Baughman, MD, emeritus professor at the University of Cincinnati in Ohio. “Treatment options for patients with sarcoidosis are limited.”
“Prednisone toxicity [a corticosteroid] is the most common complaint of patients on therapy,” said Baughman. “The steroid-sparing primary endpoint prioritized by the FDA highlights the need for new, disease-modifying treatment options that can improve clinical outcomes while reducing steroid toxicity with the goal of truly improving quality of life for patients.”
The FDA recently granted orphan drug status to efzofitimod, a designation intended to accelerate the development of treatments for rare diseases. The FDA defines such diseases as those affecting fewer than 200,000 people in the U.S.