FDA to Review Imetelstat NDA for Transfusion-Dependent Anemia in Lower-Risk MDS

• Imetelstat (GRN163L) was previously granted fast track designation by the FDA of transfusion-dependent low or intermediate-risk myelodysplastic syndrome.¹

• The FDA has up to 74 days to provide notification of the Prescription Drug User Fee Act target action date for the NDA.

• An approval application submission to European Union is planned for the fourth quarter of 2023.

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

Data from the phase 3 IMerge study (NCT02598661) support the NDA. Primary results were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, showing statistically significant and clinically meaningful efficacy in terms of transfusion independence (TI) and duration of TI. Moreover, the safety of the treatment was consistent with prior reports.^1,2

Results come from 178 patients randomized to receive either imetelstat or placebo. The 8-week TI rate was 39.85% in the imetelstat-treated population vs 15.0% in those who received placebo. This improvement in TI rate was also demonstrated across subgroups in the study, including patients with negative ring sideroblast status (RS).

The median duration of TI was 51.6 weeks among patients treated with imetelstat compared with 13.3 weeks for patients given a placebo (P < .001). A mean higher hemoglobin was also shown in the imetelstat-treated population (P < .001), as well as fewer transfusions (P = .042).

Patients with various mutations also derived benefit from imetelstat vs placebo in terms of variant allele frequency reduction. The mutational subgroups included patients with SF3B1 mutations (P < .001), TET2 mutations (P = .032), DNMT3A mutations (P = .019) and ASXL1 mutations (P = NS).

Blood cells | Image Credit: © Катерина Євтехова - www.stock.adobe.com

Thrombocytopenia and neutropenia were the most common grade 3/4 adverse events, however events of grade 3 or higher bleeding and infections were also common. Cytopenias that occurred did not last long and were manageable. Events of cytopenia were also reversible to at least a grade 2 in more than 80% of patients.

Investigators of IMerge noted that imetelstat has disease-transforming effects. The population, patients with transfusion-dependent anemia and lower-risk MDS, has a need for new and effective therapies.

“FDA acceptance of our NDA is a significant milestone for both Geron and the MDS community, as there remain few treatment options and significant unmet needs, particularly for patients with difficult-to-treat subtypes of this cancer,” said Faye Feller, MD, executive vice president and Geron’s chief medical officer. “We believe that the IMerge phase 3 data reflect the truly unique attributes of imetelstat, and, if approved, we expect imetelstat will change the standard of care in lower-risk MDS.”

In the ongoing IMerge study, up to 280 patients with TI anemia and lower-risk MDS will be enrolled. Patients in the study will be assessed for the primary end point of percentage of patients without blood transfusions during any consecutive 8-week period. The key secondary end points of the study are the number of patients with AEs, percentage of patients with red blood cell (RBC) transfusion during any consecutive 24-week period, 8-week TI, duration of RBC TI, hematologic improvement rate, complete remission rate, overall survival, progression-free survival, time to progression, number of RBC transfusions, relative change in RBC transfusions, quality of life, and the number of patients with AEs.³

Study investigators are actively recruiting patients who are 18 years of age or older with lower-risk MDS according to the International Prognostic Scoring System, and are RBC transfusion dependent with an ECOG performance score of 0, 1, or 2.

_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://tinyurl.com/yc5a5m3j}

_{2. 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}

_{3. Study to evaluate imetelstat (GRN163L) in subjects with International Prognostic Scoring System (IPSS) low or intermediate-1 risk myelodysplastic syndrome (MDS). ClinicalTrials.gov. Update July 27. 2023. Accessed August 22, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT02598661}