Imetelstat
Imetelstat
Experimental cancer drug
Imetelstat (development code GRN163L) is an experimental anticancer drug.[1] The first telomerase inhibitor to enter clinical trials,[2] As of early 2023, it was in Phase 2/3 trials for various cancer types.[which?][2]
Chemically, imetelstat is a synthetic conjugate consisting of three parts: GRN163, a thio phosphoramide oligonucleotide, and a palmitoyl lipid group.[2] GRN163 is the pharmacological component with telomerase inhibition. The palmitic acid moiety is conjugated via a phosphothioate linkage to the backbone of the antisense oligonucleotide. Telomere shortening and lower cell viability are observed after inhibition of telomerase activity in vitro. IC50 values ranged from 50 to 200nM for 10 different pancreatic cell lines. [3]
Imetelstat is being developed by Geron Corporation to treat patients with low- or intermediate-risk myelodysplastic syndromes (MDS) who are reliant on red blood cell transfusions. In 2023, Geron submitted a New Drug Application to the U.S. Food and Drug Administration (FDA) for imetelstat based on results from the phase 2/3 IMerge clinical trial (NCT02598661).[4] The IMerge trial evaluated imetelstat against placebo in 178 transfusion-dependent MDS patients who were refractory or ineligible for erythropoiesis-stimulating agents (ESAs). Results demonstrated significantly higher rates of 8-week transfusion independence with imetelstat than placebo (p<0.001), with a median duration of independence of approximately 1 year. Imetelstat also significantly increased hemoglobin levels over time compared to placebo (p<0.001). The safety profile was consistent with previous trials. If approved, imetelstat could address significant unmet needs for lower-risk MDS patients often experiencing chronic transfusion-dependent anemia.