Telomerase Inhibitor Approved for MDS-Related Anemia

— Imetelstat indicated for lower-risk myelodysplastic syndromes with transfusion-dependent anemia

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FDA APPROVED imetelstat (Rytelo) over a photo of a bag of blood in blue rubber gloved hands.

The FDA for adults with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia who failed or cannot take standard treatment, the agency announced late on Thursday.

An oligonucleotide telomerase inhibitor, imetelstat is specifically indicated for use in MDS patients requiring at least four red blood cell units over 8 weeks and who have not responded to, have lost response to, or are ineligible for erythropoiesis-stimulating agents.

Primary support for the approval came from the IMerge trial. The phase III multicenter study of 178 patients with MDS met its primary and key secondary endpoints by demonstrating significantly higher rates of red blood cell transfusion independence with imetelstat versus placebo for at least 8 consecutive weeks (40% vs 15%, P<0.001) and for at least 24 weeks (28% vs 3%, P<0.001).

Treatment with imetelstat also increased hemoglobin levels and reduced overall transfusion burden compared with placebo.

In March, the FDA's Oncologic Drugs Advisory Committee (ODAC) overwhelmingly backed the drug, despite reservations from agency staffers related to the study's 8-week primary endpoint (rather than a longer duration), potential safety risks including cytopenias, and other concerns.

"For patients with lower-risk (LR) MDS and anemia who are transfusion dependent, we have very few options today and often cycle through available therapies, making the approval of Rytelo potentially practice changing for us," IMerge investigator Rami Komrokji, MD, of the Moffitt Cancer Center in Tampa, Florida, said in from drugmaker Geron.

"What is exciting about Rytelo is the totality of the clinical benefit across LR-MDS patients irrespective of ring sideroblast status or high transfusion burden, including sustained and durable transfusion independence and increases in hemoglobin levels, all within a well-characterized safety profile of generally manageable cytopenias," said Komrokji. "The treatment goal for patients with LR-MDS and anemia is transfusion-independence and before today, this wasn't possible for many patients."

Common grade 3/4 adverse events (AEs) in patients taking imetelstat were neutropenia (68% vs 3% with placebo) and thrombocytopenia (62% vs 8%).

But at the ODAC meeting in March, panelist Neil Vasan, MD, PhD, of Columbia University Medical Center in New York City, noted that "the benefit in improvement in transfusion independence outweighed the risk of cytopenias in a patient population and a blood cancer oncology community that is well versed in these adverse events and their management."

AEs of any grade that occurred in at least 10% of patients on imetelstat in IMerge (and with a difference greater than 5% versus placebo) included decreases in platelets, white blood cells, and neutrophils; increases in aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase; as well as fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID infections, and headache.

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    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.