Novel Leukemia Drug Gets FDA Orphan Drug Designation


A first-in-class selective retinoic acid receptor alpha agonist is being tested in phase 2 clinical trials for acute myeloid leukemia and myelodysplastic syndrome.

Syros Pharmaceuticals recently announced that the FDA granted orphan drug designation to SY-1425, an experimental drug for the treatment of acute myeloid leukemia (AML), according to a press release.

SY-1425 is a first-in-class selective retinoic acid receptor alpha (RARA) agonist that is being tested in phase 2 clinical trials. Syros reported that the drug is being developed for a set of patients who have AML and myelodysplastic syndrome (MDS) along with the overexpression of 2 genes.

By harnessing its gene control platform, Syros discovered subsets of patients with AML and MDS with super-enhancers linked to RARA or interferon regulatory factor 8 (IRF8), according to the release.

Syros then found biomarkers for the super-enhancers, which are thought to drive the heightened expression of the genes. Overexpression of RARA or IRF8 genes causes cells to remain immature and undifferentiated while proliferating, which can lead to diseases.

Preclinical studies showed that treatment with SY-1425 led to differentiation of AML cells with heightened expression of the genes, according to the release. The drug also inhibited tumor growth and increased survival in patient xenograft models.

The ongoing phase 2 clinical trial is exploring the safety and efficacy of SY-1425 as a monotherapy in patients with SML and MDS. SY-1425 is also being evaluated in combination with azacitidine chemotherapy in newly-diagnosed patients. All patients included in the trial were selected using biomarkers that indicate overexpression of RARA and IRF8.

Syros projects that one-third of AML and MDS patients have the biomarker for either gene or both, according to the release. The new drug may help these patients receive more targeted treatment, leading to better survival.

“Treatment of AML remains a significant unmet medical need, with many patients lacking adequate therapeutic options,” said David A. Roth, MD, chief medical officer at Syros. “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. 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.”

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