FDA Accepts New Drug Application for Imetelstat in Lower-Risk MDS

The FDA set a Prescription Drug User Fee Act date of June 16, 2024 for imetelstat in the management of lower-risk MDS.

The FDA has accepted a new drug application (NDA) for imetelstat as a treatment for patients with transfusion-dependent anemia in lower-risk myelodysplastic syndromes (MDS), according to a press release from Geron Corporation.¹

The regulatory agency set a Prescription Drug User Fee Act date of June 16, 2024 for the NDA.²

Supporting data for the NDA came from the phase 3 portion of the phase 2/3 IMerge trial (NCT02598661), in which imetelstat produced a significant improvement in 8-week transfusion independence compared with placebo (P <.001). Investigators also reported a significant increase in mean hemoglobin levels in patients receiving the experimental agent compared with those receiving placebo (P <.001). Data also highlighted clinically meaningful and statistically significant benefits with imetelstat across patient subgroups regardless of ring sideroblast status, baseline transfusion burden, and International Prognostic Scoring System (IPSS) risk disease.

The safety profile of imetelstat in the IMerge trial was comparable with prior reports of the agent. According to findings presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, common any-grade adverse effects in patients treated with imetelstat included thrombocytopenia (75%), neutropenia (74%), anemia (20%), COVID-19 (19%), and asthenia (19%).³

“The FDA’s acceptance of our [NDA] is an important landmark along our steadfast journey to bring telomerase inhibition with imetelstat to the market,” John A. Scarlett, MD, chairman and chief executive officer at Geron, said in the press release.¹ “We look forward to continuing our collaboration with the FDA toward the goal of bringing imetelstat to the many patients for whom we believe this treatment could make a significant difference.”

Investigators of the double-blind, placebo-controlled phase 2/3 IMerge trial assessed imetelstat in 178 patients with IPSS low or intermediate-1 risk transfusion dependent MDS that is relapsed or refractory following treatment with erythropoiesis stimulating agents. Patients were randomly assigned 2:1 to receive 7.5 mg/kg of imetelstat intravenously every 4 weeks or matched placebo.

The trial’s primary end point was the rate of red blood cell transfusion independence sustained for at least 8 weeks, which investigators defined as the proportion of patients without any red blood cell transfusion for a minimum of 8 consecutive weeks. Secondary end points included rate of red blood cell transfusion independence sustained for at least 24 weeks, duration of transfusion independence, and rate of hematologic improvement erythroid.

Patients 18 years and older who were transfusion dependent, defined as requiring at least 4 red blood cell units transfused over 8 weeks within 16 weeks prior to study entry, were eligible for enrollment on the trial. Patients also needed to have an ECOG performance status of 0 to 2 to enroll on the trial.

Developers submitted the NDA for imetelstat in lower-risk MDS in June 2023.⁴

References

1. Geron announces FDA acceptance of new drug application for imetelstat for the treatment of lower risk MDS. News release. Geron Corporation. August 21, 2023. Accessed August 22, 2023. https://shorturl.at/DOYZ6
2. Geron announces PDUFA date for imetelstat NDA in lower risk MDS. News release. Geron Corporation. August 22, 2023. Accessed August 22, 2023. https://shorturl.at/GMSU6
3. Zeidan AM, Platzbecker U, Santini V, et al. IMerge: results from a phase 3, randomized, double-blind, placebo-controlled study of imetelstat in patients (pts) with heavily transfusion dependent (TD) non-del(5q) lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA). J Clin Oncol. 2023;41(suppl 16):7004. doi:10.1200/JCO.2023.41.16_suppl.7004
4. Geron announces submission of new drug application to FDA for first-in-class telomerase inhibitor imetelstat. News release. Geron Corporation. June 20, 2023. Accessed August 22, 2023. https://bit.ly/3CFbD8l