Imetelstat Study Blip Beats Geron’s Shares Down

Shares in Geron dropped by nearly 20% to $2.30 on NASDAQ on Sept. 12 following interim clinical data for its lead product, the anticancer imetelstat, from trials conducted by its partner Janssen.

While the studies – IMbark and IMerge – are both still ongoing investors were spooked by the news that Janssen was going to drop the lower dose arm in one of them, IMbark, in myelofibrosis. Imetelstat is Geron Corp.’s only real pipeline asset.

Janssen R&D LLC is conducting the two late-stage trials of the telomerase inhibitor following a licensing deal signed back in November 2014. The deal was a boon for the Menlo Park, California-based Geron, coming just weeks after the FDA lifted a clinical hold on the company’s Phase II program for the product. The hold was put in place earlier that year following concerns over the potential for liver injury in March that year. (Also see "FDA slaps hold on imetelstat studies; Geron whipped" - Scrip, 13 Mar, 2014.) But better news came in November when an investigator-sponsored study showed imetelstat produced four complete remissions and one partial remission in myelofibrosis patients. (Also see "Geron soars on Mayo Clinic results for imetelstat" - Scrip, 8 Nov, 2013.)

Telomerase has long been a target in cancer drug development but has produced little fruit so far. In South Korea a vaccine based on telomerase peptides was launched by Samsung in 2015 for advanced/metastatic pancreatic cancer and some other vaccine-type products are in early stage development.

The first-in-class imetelstat is a specially designed and modified short oligonucleotide, which targets and binds directly with high affinity to the active site of telomerase. It appears to be the most advanced telomerase inhibitor currently in development and there is little else still active in the pipeline, although the discontinued products seem to have been aimed more at solid rather than blood cancers.

Studies

The IMBark study was originally designed as a Phase II trial to evaluate two doses of imetelstat (4.7 mg/kg or 9.4 mg/kg every three weeks) in about 200 patients with intermediate-2 or high-risk myelofibrosis who have relapsed after or are refractory to prior treatment with a JAK inhibitor.

The co-primary efficacy endpoints for the trial are spleen response rate and symptom response rate at 24 weeks. So far, more than 90 patients have been enrolled in the trial across both dosing arms, and the interim analysis looked at data from 20 patients from each dosing arm at the 12-week time-point.

While the safety data were consistent with previous trials in hematological malignancies, Janssen noted that the activity seen in the 4.7 mg/kg was not sufficient to warrant further investigation. This arm will now be closed to further enrolment and subject to a protocol amendment, patients switched to the 9.4 mg/kg arm.

Janssen found that even though an insufficient number of patients met the protocol-defined interim criteria at 12 weeks the higher-dose arm was worth pursuing because of encouraging trends. Still, new enrolment in this arm will be suspended while additional and more mature data are obtained, including a longer follow-up of patients at 24 weeks. It said the number of patients enrolled to date is expected to be sufficient to inform potential future development of this dose.

The second study, IMerge is a Phase II/III trial of imetelstat in transfusion dependent patients with low or intermediate-1 risk myelodysplastic syndromes who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent. This study is to continue unmodified after a review of the first, Phase II, part of the trial in a subset of the 30 patients enrolled.

A further assessment of IMerge is due in the second quarter of next year when a decision will be made on whether or not to proceed the second, Phase III, part of the trial. If Janssen does proceed then enrolment for this will begin mid-next year.