Syros' Tamibarotene Fails in Phase III Trial for Higher-Risk Myelodysplastic Syndrome
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Syros Pharmaceuticals' stock plummeted after its Phase III SELECT-MDS-1 trial of tamibarotene plus azacitidine failed to meet the primary endpoint in higher-risk myelodysplastic syndrome (search) (HR-MDS) patients.
The trial, involving 190 patients, showed similar complete response rates in both the treatment (23.8%) and placebo (18.8%) groups, leading to the discontinuation of the study.
This setback follows a previous Phase II trial of tamibarotene in acute myeloid leukemia (search) (AML) that was unlikely to meet its primary endpoint, further impacting investor confidence.
Syros Pharmaceuticals' stock experienced a significant drop after its Phase III SELECT-MDS-1 trial, evaluating tamibarotene in combination with azacitidine for newly diagnosed higher-risk myelodysplastic syndrome (search) (HR-MDS) patients with RARA gene (search) overexpression, failed to meet its primary endpoint. The company plans to discontinue the study and thoroughly review the results to determine the next steps.
The placebo-controlled Phase III study enrolled 190 patients. The primary endpoint, complete response rate, was 23.8% in the treatment group and 18.8% in the placebo group. Syros reported that the therapy was well-tolerated.
This news comes shortly after Syros reported that a Phase II SELECT-AML-1 trial evaluating the same combination treatment in patients with acute myeloid leukemia (search) (AML) was unlikely to meet its primary endpoint. An interim futility analysis indicated a low probability of success based on data from the first 40 randomized patients.
According to Syros, the failure of the SELECT-MDS-1 Phase III trial to meet its endpoint constitutes a default event under its secured loan facility with Oxford Finance. The company had secured a $60 million senior secured loan facility in 2022.
Tamibarotene is a specific agonist of retinoic acid receptor alpha/beta with possible binding to retinoid X receptors (RXR). The RXR receptors regulate the transcription of signalling pathways that impact numerous hallmarks of cancer by controlling both inflammation and immune responses that modulate the tumour microenvironment.