FDA Awards Fast Track Designation to Tamibarotene for Increased-Risk MDS


The FDA has granted a fast track designation to tamibarotene for the treatment of higher-risk myelodysplastic syndrome.

The FDA has granted a fast track designation to tamibarotene for the treatment of higher-risk myelodysplastic syndrome (HR-MDS), according to an announcement from Syros Pharmaceuticals. The oral, first-in-class selective retinoic acid receptor alpha (RARα) agonist is currently being evaluated in combination with azacitidine for the treatment of newly diagnosed HR-MDS patients with RARA gene overexpression.

“Receipt of fast track designation for tamibarotene underscores both the potential of tamibarotene and the unmet need for HR-MDS patients, who have a poor prognosis due to the progressive nature of the disease,” Syros chief medical officer David A. Roth, MD, said in a news release. “No new therapies beyond hypomethylating agents have been approved since 2006, and approximately half of all patients diagnosed with HR-MDS…ultimately progress to AML.”

According to previous findings, approximately 30% of patients with HR-MDS are RARA positive. Tamibarotene demonstrated myeloid differentiation, improved blood counts, and reduced bone marrow blasts in this patient population in previous findings.

Syros is evaluating tamibarotene in combination with azacitidine for patients with RARA-overexpressed HR-MDS in the ongoing phase 3 SELECT-MDS-1 trial (NCT04797780). This randomized, double-blind, placebo-controlled study opened in February 2021 with a plan to enroll 190 patients. Investigators will randomly assign participants in a 2:1 fashion to azacitidine plus tamibarotene or placebo.2

In June 2022, Gustavo Rivero, MD, an associate professor of medicine-hematology & oncology with the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, spoke with OncLive® about the SELECT MDS-1 trial. He noted that most of the data in MDS was extrapolated from studies of acute myeloid leukemia (AML), but there is an unmet need because almost all patients become refractory to the standard treatments of azacitidine and decitabine.

“Tamibarotene is a RARA agonist that creates a balance between the ligand, which is retinoic acid, and RARAoverexpression by itself,” he said. “By restoring RARA, acute differentiation might occur in cells that are specifically leukemic, but in the case of MDS, it is expected to leave about the same clinical benefit.”

Syros currently has over 75 clinical sites open for recruitment in 12 countries and expects to complete patient enrollment in the fourth quarter of 2023. The company expects to present pivotal data in the third quarter of 2024.

Syros is also evaluating tamibarotene in combination with venetoclax (Venclexta) and azacitidine in newly diagnosed unfit patients with RARA-positive AML. Initial data from the randomized portion of the SELECT-AML-1 phase 2 trial (NCT04905407) are expected in the fourth quarter of 2023, with additional data presented in 2024.


  1. Syros receives fast track designation from the FDA for tamibarotene for the treatment of higher-risk myelodysplastic syndrome. News release. Syros Pharmaceuticals. January 26, 2023. Accessed January 26, 2023.
  2. Dezern AE, Marconi G, Deeren D, et al. A randomized, double-blind, placebo-controlled study of tamibarotene/azacitidine versus placebo/azacitidine in newly diagnosed adult patients selected for RARA+ HR-MDS (SELECT-MDS-1). J Clin Oncol. 2022;40:(suppl 16):TPS7075. doi:10.1200/JCO.2022.40.16_suppl.TPS7075
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