Despite skepticism from FDA reviewers, the Oncologic Drugs Advisory Committee on Thursday strongly supported Geron’s imetelstat for the treatment of anemia in patients with lower-risk myelodysplastic syndromes.
Pictured: Illustration of blood cells being produced in the bone marrow/iStock, Artur Plawgo
The FDA’s Oncologic Drugs Advisory Committee on Thursday voted 12–2 in favor of Geron Corporation, finding that its investigational telomerase blocker imetelstat had a favorable benefit/risk profile for the treatment of transfusion-dependent anemia in patients with lower-risk myelodysplastic syndromes.
Members of the advisory committee highlighted that imetelstat met its primary efficacy endpoint in the Phase III MDS3001 study, demonstrating a statistically significant improvement in red blood cell transfusion independence. Panelists also expressed confidence that side effects for imetelstat treatment could be managed by the patients’ healthcare providers.
Neil Vasan, assistant professor of the Division of Hematology & Oncology at Columbia University Medical Center, said during the meeting that imetelstat “offers a new therapy for some patients who may have no other option depending on their MDS classification.” Vasan voted in favor of Geron.
“I felt that the benefits of improvement in transfusion independence outweigh the risk of cytopenias in a patient population and a blood cancer oncology community that’s well-versed in these adverse events and their management,” Vasan said.
In a statement following the vote, Geron CMO Faye Feller said that the company is “pleased” with the outcome of the advisory committee meeting, which recognizes the “positive clinical benefit/risk profile of imetelstat” and its “potential to be an important new medicine for patients.”
Still, some of the FDA’s external experts were unconvinced by imetelstat’s performance, particularly its safety and adverse event profiles. In MDS3001, Geron’s candidate demonstrated a high rate of Grade 3 to 4 neutropenia and thrombocytopenia cases, and more patients treated with imetelstat needed platelet transfusions and myeloid growth factors versus placebo.
Ravi Madan, chairperson of the advisory committee and head of the prostate cancer clinical research section at the National Cancer Institute, was one of two panelists who voted against Geron. In explaining his vote, Madan noted that he “interpreted the question very strictly.”
“Even low-risk MDS patients are at high risk from their disease, but they shouldn’t also be at risk from their treatments, as well,” Madan said. “While a significant minority of patients clearly benefited from imetelstat, majority of patients did not derive benefit, and that combined with the increased toxicity of the agent … makes the data less clear to me that the risks totally outweigh the benefits.”
The FDA’s internal staffers also flagged imetelstat’s safety risks in a briefing document published ahead of the advisory committee meeting. The regulator’s reviewers also pointed out that imetelstat failed key secondary endpoints—including complete and partial remission, overall survival and patient-reported outcomes—which they observed could be suggestive of a disease-modifying effect.
Because of these factors, combined with “residual uncertainties” such as the low number of U.S. patients enrolled, the FDA’s briefing document concluded that “it is not clear that the risks of treatment with imetelstat are outweighed by the potential benefit for the intended population.”
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
