Syros Reports Phase 3 SELECT-MDS-1 Data on Tamibarotene for High-Risk Myelodysplastic Syndrome with RARA Overexpression

Syros Pharmaceuticals, a biopharmaceutical company based in Cambridge, Massachusetts, focused on pioneering new treatments for hematologic cancers, recently disclosed the outcomes of its SELECT-MDS-1 Phase 3 clinical trial. This trial was designed to evaluate the efficacy of tamibarotene, combined with azacitidine, in treating newly diagnosed patients with higher-risk myelodysplastic syndrome (HR-MDS) who exhibit overexpression of the RARA gene. Unfortunately, the trial did not achieve its primary goal of significantly improving the complete response (CR) rate.

Tamibarotene is a proprietary oral drug developed by Syros, targeting the retinoic acid receptor alpha (RARα). In the trial, the CR rate among the first 190 patients treated with tamibarotene and azacitidine was 23.8%, compared to an 18.8% CR rate in the control group receiving a placebo and azacitidine. Despite the higher response in the treatment group, the difference was not statistically significant, with a p-value of 0.2084.

The safety profile for the combination of tamibarotene and azacitidine was consistent with previous studies, indicating that the combination was generally well-tolerated among patients. Specifically, in the safety analysis involving all 245 enrolled patients, the adverse events observed were similar to those reported in earlier trials sponsored by Syros.

The failure to meet the primary endpoint triggers a default event under Syros’s loan agreement with Oxford Finance LLC, as noted in earlier financial disclosures. This outcome has significant implications for the company, leading to a reassessment of their clinical strategy.

Conley Chee, the CEO of Syros, expressed profound disappointment over the trial results, emphasizing the impact on HR-MDS patients who are in urgent need of new treatment options. He stated that the company intends to halt the study, conduct a more detailed analysis of the clinical data, and determine subsequent steps. Chee also conveyed gratitude toward the patients, caregivers, healthcare professionals, and Syros employees involved in the SELECT-MDS-1 trial for their contributions and dedication.

The SELECT-MDS-1 was an international, randomized, double-blind, placebo-controlled Phase 3 trial. Its objective was to compare the safety and efficacy of tamibarotene in combination with azacitidine versus placebo combined with azacitidine in HR-MDS patients with RARA overexpression. The primary endpoint was assessing the CR rate in the initial 190 patients enrolled in the study.

Syros remains dedicated to developing innovative treatments for patients with hematologic malignancies. The company is driven by the goal of improving outcomes for patients with blood disorders that have historically been difficult to treat with targeted therapies. Tamibarotene, an oral selective RARα agonist, is being developed for frontline patients with higher-risk myelodysplastic syndrome characterized by RARA gene overexpression.

Despite the setback in the SELECT-MDS-1 trial, Syros continues to explore avenues to advance its research and bring new therapeutic options to patients in need.