AML cells
The US Food and Drug Administration (FDA) has granted orphan drug designation to SY-1425 for the treatment of acute myeloid leukemia (AML).
SY-1425 is an oral, first-in-class, selective retinoic acid receptor alpha (RARα) agonist. It is currently under investigation in a phase 2 trial of patients with AML and myelodysplastic syndromes (MDS).
“We believe that SY-1425 may provide a meaningful benefit for subsets of AML patients whose disease is driven by abnormally high expression of the RARA or IRF8 genes,” said David A. Roth, MD, chief medical officer at Syros Pharmaceuticals, the company developing SY-1425.
“Receiving orphan drug designation is an important regulatory milestone in the development of SY-1425. We’re pleased with the continued progress of the ongoing phase 2 clinical trial, and we look forward to presenting initial clinical data in the fourth quarter of this year.”
Using its gene control platform, Syros discovered subsets of AML and MDS patients with super-enhancers associated with RARA or IRF8. These super-enhancers are believed to drive overexpression of the RARA or IRF8 genes, locking cells in an immature, undifferentiated, and proliferative state and leading to disease.
In preclinical studies, SY-1425 promoted differentiation of AML cells with high RARA or IRF8 expression and inhibited tumor growth and prolonged survival in patient-derived xenograft models of AML with high RARA expression.
In the ongoing phase 2 trial, researchers are assessing the safety and efficacy of SY-1425 as a single agent in 4 AML and MDS patient populations, as well as SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.
All patients are prospectively selected using biomarkers for high expression of RARA or IRF8. Additional details about the trial can be found at https://clinicaltrials.gov/ct2/show/NCT02807558.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
