FDA Green Lights Fast Track Designation to Tamibarotene for Higher-Risk MDS

The FDA has granted a fast track designation to tamibarotene (Amnolake) for the treatment of higher-risk myelodysplastic syndrome (HR-MDS), according to Syros Pharmaceuticals, Inc.¹

Tamibarotene is an oral first-in-class selective retinoic acid receptor alpha (RARα) agonist that is currently under investigation in combination with azacitidine (Vidaza) for patients with HR-MDS who have RARAgene overexpression.

The ongoing, randomized, double-blind, placebo-controlled study, phase 3 SELECT MDS-1 trial (NCT04797780) is evaluating the agent in combination with venetoclax (Venclexta) and azacitidine in this patient population.^1,2

"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," said David A. Roth, MD, chief medical officer of Syros Pharmaceuticals, Inc, in the press release.1 "No new therapies beyond hypomethylating agents have been approved since 2006, and approximately half of all patients diagnosed with HR-MDS patients ultimately progress to AML. We are grateful for the opportunity to potentially expedite the delivery of tamibarotene as a new standard of care for this population."

In the ongoing phase 3 SELECT MDS-1, a total of 190 patients aged 18 years and older with newly-diagnosed HR-MDS are expected to be enrolled across over 75 clinical sites in 12 countries. Patients are required to have a diagnosis of MDS according to the World Health Organization classification and the Revised International Prognostic Scoring System risk category as very-high, high, or intermediate risk, and an ECOG performance status of 0-2 to enroll in the trial.2

Patients who are suitable for and agree to undergo allogeneic hematopoietic stem cell transplantation (HSCT) at the time of screening and those who have been given previous treatment for their MDS with a hypomethylating agent, chemotherapy or allogeneic HSCT will be excluded from the trial

The combination tamibarotene at 6 mg orally twice a day given on days 8-28 of each treatment cycle and azacitidine at 75 mg/m2 via intravenous (IV) or subcutaneous administration of days 1-7 of each cycle will be administered in the experimental arm of the study. Then in the placebo arm, patients will be given the same treatment regimen as those in the experimental arm but using a tamibarotene matched placebo.

Investigators are evaluating the primary end point of patients with complete remission and the secondary end points of proportion of patients who achieve objective response and transfusion independence, duration of event-free survival, overall survival, complete response, overall response, time to complete remission, time to initial response, and safety, including the proportion of patients with adverse events (AEs) and serious AEs.

Patient enrollment for the SELECT-MDS-1 trial is expected to be completed by the end of 2023 and pivotal data from the trial are anticipated some time in 2024.

In addition to the SELECT-MDS-1 study, tamibarotene is also being evaluated in combination with venetoclax and azacitidine for patients with newly diagnosed unfit acute myeloid leukemia who have RARA overexpression. Initial data from the randomized portion of this phase 2 trial are expected by the end of 2023.

References:

Syros receives fast track designation from the FDA for tamibarotene for the treatment of higher-risk myelodysplastic syndrome. News release. Syros Pharmaceuticals, Inc. January 26, 2023. Accessed January 27, 2023. https://yhoo.it/3HbGtXV

Tamibarotene plus azacitidine in participants with newly diagnosed RARA-positive higher-risk myelodysplastic syndrome. ClinicalTrials.gov. Updated January 9, 2023. Accessed January 27, 2023. https://clinicaltrials.gov/ct2/show/NCT04797780