Geron (GERN) imetelstat can potentially bring about a paradigm shift in non-solid cancer therapeutics. Imet inhibits telomerase, an enzyme that enables malignant cells to replicate with its DNA intact by protecting the ends of chromosomes. Most types of tumors use the telomerase pathway to replicate, and therefore, this approach has the potential to bring about great therapeutic benefit.
Currently, Geron, with its partner Janssen (JNJ), has two trials ongoing for imetelstat - IMbark, a Phase 2 trial in myelofibrosis (MF) and IMerge, a Phase 2/3 trial in myelodysplastic syndromes (MDS). Geron is awaiting Janssen’s decision to continue with part 2 of the IMerge trial based on “Feedback from ongoing FDA interactions, data from the expanded Part 1, and other imetelstat program information, including the protocol-specified primary analysis for IMbark, are expected to inform Janssen’s decision of whether to move forward to Part 2 of IMerge.” A subset of 13 patients of the 32 total enrolled patients who had not received prior treatment with either a hypomethylating agent (HMA) or lenalidomide and did not have a del(5q) chromosomal abnormality showed an increased durability and rate of transfusion independence compared to the overall trial population (≥8-week RBC-TI: 53.8% vs 34.4%). An additional 20 patients who are non-del5q and naïve to HMA and lenalidomide treatment are being enrolled to verify this data. The press release quoted does not discuss data from the other 19 patients.
The other trial, IMbark, is a Phase 2 trial in patients with Intermediate-2 or High Risk MF who have relapsed after or are refractory to prior treatment with a JAK inhibitor. This trial continues as planned, and to date, median overall survival has not yet been reached in either the 4.7 mg/kg or 9.4 mg/kg dosing arm. Janssen will provide details of whether it continues or not upon the earlier of either a pre-specified number of deaths occurring in the trial or the end of the third quarter of 2018. Basically, both trials currently hang in the balance, but the IMbark trial looks more likely to continue with Janssen - that is our opinion. If Janssen continues, the opt-in/out considerations will set in for Geron, and we have two scenarios here.
