FDA Approves Geron Corporation’s Rytelo to Treat Adults with Lower-Risk Myelodysplastic Syndromes

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Geron Corporation announced that the FDA has approved Rytelo (imetelstat), a telomerase inhibitor for the treatment of adult patients with lower-risk myelodysplastic syndromes (MDS) who have transfusion-dependent anemia and who have not responded to or are ineligible for erythropoiesis-stimulating agents (ESA). According to the company, the approval was based on results from the IMerge Phase III clinical trial, which demonstrated significantly higher rates of red blood cell transfusion independence (RBC-TI) with Rytelo compared to a placebo, in periods of both eight weeks consecutively and a minimum of 24 weeks.

Geron stated that this approval has the potential to help patients reduce the need for red blood cell transfusions and alleviation of symptomatic anemia.¹

“With the approval and availability of Rytelo, we believe eligible patients with lower-risk MDS can potentially experience meaningful clinical benefit, particularly the potential for greater than 24 weeks of freedom from the burden of red blood cell transfusions and symptomatic anemia,” said John A. Scarlett, MD, chairman, CEO, Geron Corporation, in a press release. “The approval of Rytelo as the first telomerase inhibitor is a testament to the power of our science and the passion of our people to innovate in the field of blood cancer. As we celebrate today’s momentous milestone, I would like to thank the patients and families, advocates, clinicians, study coordinators and site personnel, scientists, and Geron employees and collaborators past and present whose participation was integral to this achievement and to supporting our transformation into a commercial company.”

The double-blind, placebo-controlled IMerge trial was conducted across 118 sites, including university hospitals, cancer centers, and outpatient clinics in 17 countries. Additionally, a total of 178 patients were randomly assigned to one of two cohort, with 118 patients treated with Rytelo and 60 administered a placebo. The primary endpoint of the study was RBC-TI throughout eight weeks. For those enrolled in the Rytelo arm of the study, treatment consisted of a 7.5 mg dose, administered as a 2-h intravenous infusion every four weeks until disease progression, unacceptable toxic effects, or withdrawal of consent.²

Results show that 39.8% of patients treated with Rytelo achieved RBC-TI, while only 15% of those in the placebo arm experienced the same result. Additionally, 28% of Rytelo patients maintained their RBC-TI for 24 weeks, compared to only 3.3% in the placebo group. Notably, RBC-TI lasted approximately one year for eight-week responders and 1.5 years for 24-week responders. Further, the treatment reportedly increased hemoglobin levels across key MDS subgroups.

In terms of safety, the most common adverse events (AEs) were thrombocytopenia and neutropenia, both of which were grade 3/4, typically manageable, and resolved within 80% of participants in under four weeks. Other common AEs included laboratory abnormalities, fatigue, arthralgia/myalgia, and headache.¹

“For patients with lower-risk 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,” said Rami Komrokji, MD, vice chair, malignant hematology department, Moffitt Cancer Center, IMerge clinical trial investigator, in the press release. “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. The treatment goal for patients with LR-MDS and anemia is transfusion-independence and before today, this wasn’t possible for many patients.”

References

1. Geron Announces FDA Approval of RYTELO™ (imetelstat), a First-in-Class Telomerase Inhibitor, for the Treatment of Adult Patients with Lower-Risk MDS with Transfusion-Dependent Anemia. Geron. June 6, 2024. Accessed June 7, 2024. https://ir.geron.com/investors/press-releases/press-release-details/2024/Geron-Announces-FDA-Approval-of-RYTELO-imetelstat-a-First-in-Class-Telomerase-Inhibitor-for-the-Treatment-of-Adult-Patients-with-Lower-Risk-MDS-with-Transfusion-Dependent-Anemia/default.aspx

2. Platzbecker, U. et al. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. Volume 403, Issue 10423, P249-260. Jan 20, 2024.