After the U.S. Food and Drug Administration accepted aTyr Pharma‘s investigational new drug application for ATYR1923, the company announced it will initiate a Phase 1b/2a clinical trial in patients with pulmonary sarcoidosis.
The company will collaborate with the Foundation for Sarcoidosis Research (FSR) for the development of the trial.
Sarcoidosis is characterized by the formation of granulomas — clumps of inflammatory cells — in one or more organs. The prognosis ranges from benign and self-limiting to chronic, debilitating, and life-threatening.
Current medical treatment for sarcoidosis and interstitial lung diseases generally consists of anti-inflammatory medicines, such as corticosteroids, and organ transplant if the lungs, heart or liver become severely damaged. Therefore, there is a medical necessity for a long-term treatment option.
aTyr scientists developed ATYR1923 as a potential therapeutic for patients with sarcoidosis. ATYR1923 is a fusion protein that has two parts: the immuno-modulatory domain of histidyl tRNA synthetase (HARS), part of the Resokine pathway, fused to the FC region of a human antibody. This pathway is known to regulate immune responses and includes the Neuropilin-2 (NRP-2) receptor protein. ATYR1923 is able to bind to NRP-2, enhancing the Resokine pathway, with a focus on immune responses affecting the lungs.
In a first-in-human Phase 1 clinical trial (ACTRN12617001446358), aTyr scientists investigated the safety, tolerability, immunogenicity (ability to provoke an immune response), and pharmacokinetics (how the body processes the therapy) — of ATYR1923 in 36 healthy volunteers.
Administration of ATYR1923 reduced T cell activation, decreased cytokine production from T cells, and ultimately relieved lung fibrosis. These promising results indicated that ATYR1923 was largely well-tolerated at all dosages tested with no significant adverse effects, and the observed pharmacological profile supported the potential for a once-monthly dosing regimen.
The multiple-ascending dose, placebo-controlled Phase 1b/2 trial is designed to evaluate the safety, tolerability, and immunogenicity of multiple doses of ATYR1923. In addition, the Phase 1b/2a study will help establish clinical endpoints and potential biomarkers to assess preliminary efficacy of ATYR1923 in pulmonary sarcoidosis patients.
“We accomplished our previously stated goal of initiating this proof-of-concept Phase 1b/2a study of ATYR1923 this quarter, and we look forward to data that we believe will demonstrate the first signals of clinical activity in pulmonary sarcoidosis patients,” Sanjay Shukla, M.D., M.S., President and Chief Executive Officer of aTyr, said in a press release.
In addition, aTyr announced that it is partnering with the FSR, a leading nonprofit organization devoted to improving care for sarcoidosis patients and finding a cure for sarcoidosis. FSR’s role in the collaboration will be clinical trial site initiation and patient enrollment.
aTyr anticipates that the study will have up to 12 participating sites in the United States. This clinical trial has the support of FSR’s Clinical Studies Network, led by a steering committee of principal investigators from leading clinical centers.
“We are pleased to collaborate with the team at aTyr Pharma as they work to advance clinical development of a promising new treatment for pulmonary sarcoidosis, a potentially debilitating inflammatory lung disease with no known cure,” said Ginger Spitzer, executive director of FSR. “Any step supporting the study of a new therapeutic candidate is a step toward a potential groundbreaking discovery that could improve the lives of sarcoidosis patients worldwide.”