In a 12-2 vote, members of the U.S. Food and Drug Administration’s Oncologic Drugs Advisory Committee (ODAC) voted in favor of imetelstat as a treatment for anemia in patients with lower-risk myelodysplastic syndromes (MDS).
The drug, a telomerase inhibitor, was submitted to ODAC by Geron Corporation with a proposed indication to treat transfusion-dependent anemia in adult patients with lower-risk MDS who do not or no longer respond to or are ineligible for the standard frontline therapy of erythropoiesis-stimulating agents (ESAs). This proposed indication is based primarily on findings from the phase III IMerge trial, in which 178 adult patients with transfusion-dependent anemia and lower-risk MDS who were ineligible for or unresponsive to ESAs were randomized 2:1 to receive imetelstat or placebo. The trial met its primary endpoint of eight-week red blood cell transfusion independence (RBC-TI; 39.8% imetelstat vs. 15.0% placebo; p≤0.001), and a key secondary endpoint of 24-week RBC-TI (28.0% imetelstat vs. 3.3% placebo; p≤0.001).
In assessing the drug, ODAC members evaluated key efficacy concerns, including a low incidence of complete or partial remission and a lack of evidence indicating an overall survival benefit. Additionally, members discussed safety issues accompanying imetelstat’s administration, most notably higher rates of neutropenia and thrombocytopenia, as well as a greater frequency of adverse reactions in these patients, including hepatic toxicity, fatigue, arthralgia or myalgia, and fractures.
“Even [patients with] low-risk MDS are at high risk for their disease, but they shouldn’t also be at risk from their treatments,” said ODAC chair Ravi Madan, MD, of the National Cancer Institute. “While a significant minority of patients clearly benefited from imetelstat, the majority of patients do not derive benefit … The increased toxicity the agent has seen with infections and bleeding and platelet transfusions makes the data less clear … that the risks totally outweigh the benefits.”
However, members of the committee ultimately voted to approve the drug.
“I believe that safety [risks] can be addressed and overcome in an MDS clinic easily,” said ODAC member Jacqueline Garcia, MD, of Dana-Farber Cancer Center in Boston. “Transfusion independence is a measure of quality of life for [patients with] lower-risk MDS that is truly meaningful. I was very impressed … by how long the responses could be among the responders [to] this therapy.”
Neil Vasan, MD, PhD, of Columbia University was among the members who voted in favor of the drug. “This trial…offers a new therapy for some patients who may have no other option depending on their MDS classification,” he said.
Source: FDA, March 14, 2024.
