FDA Sets Review Date for First-in-Class Therapy for MDS

The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of June 16, 2024, for Geron’s new drug application (NDA) for imetelstat, a first-in-class treatment to treat transfusion-dependent anemia in patients with lower risk myelodysplastic syndromes (MDS). In addition, the FDA informed the Company that it is currently planning to hold an advisory committee meeting as part of the NDA review.

Myelodysplastic syndromes are a group of cancers in which blood stem cells do not mature. This can lead to anemia, infection or bleeding. Transfusions help manage systems and can slow progression to leukemia.

Imetelstat targets telomerase to inhibit uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies. Telomerase is a naturally occurring enzyme that maintains telomeres, a protein structure at both ends of each chromosome that protects the chromosome from becoming frayed. Each time a cell divides, the telomeres become shorter; telomerase stops this from happening.

Telomerase expression has been found to be present in about 90% of biopsies taken from a broad range of human cancers, according to Geron. This drives cancer cells to continue to divide and grow. Imetelstat was designed to inhibit telomerase, selectively killing the malignant stem and progenitor cells in the bone marrow.

Geron submitted an NDA in June 2023 based on data from the phase 3 study IMerge to evaluate imetelstat versus placebo, which were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in June. The primary endpoint of transfusion independence at eight weeks was met for imetelstat-treated patients (39.8%) vs. placebo (15.0%). Key secondary endpoint of 24-week transfusion independence and Additionally, mean hemoglobin levels in imetelstat-treated patients increased over time compared with placebo. Imetelstat-treated patients also experienced a clinically meaningful mean reduction in red blood cell transfusions compared with placebo.

The safety profile observed with imetelstat in IMerge phase 3 was consistent with prior clinical experience with no new safety signals. Non-hematologic adverse events were generally low grade.

Geron has also initiated an Expanded Access Protocol (EAP), making imetelstat available to clinicians and patients prior to potential FDA approval. This program is available to patients who have relapsed or are ineligible for erythropoiesis-stimulating agents.

Faye Feller, M.D.

“We have heard physicians in both academic and community settings express the need for new treatment options for their lower risk MDS patients, and they will now have an option to access imetelstat through the EAP,” Faye Feller, M.D., executive vice president, chief medical officer of Geron, said in a press release.

The company continues research of imetelstat with IMpactMF, a phase 3 trial in patients with myelofibrosis (MF) relapsed/refractory to JAK-inhibitors. An interim analysis is expected in the first half of 2025, and final analysis is expected in the first half of 2026. The phase 2 IMpress trial is evaluating imetelstat in patients with relapsed/refractory acute myeloid leukemia or higher risk MDS.