Geron’s sole treatment imetelstat was placed on full clinical hold by the FDA, the company acknowledged today, after Phase II studies linked the blood cancer treatment to persistent low-grade liver function test (LFT) abnormalities, raising agency concerns about the potential risk of chronic liver injury following long-term exposure to the first-in-class telomerase inhibitor.
“The FDA expressed concern about whether these LFT abnormalities are reversible,” Geron said in a statement, adding that it “plans to work diligently with the FDA to seek the release of the clinical hold.
The clinical hold affects eight remaining patients in a Phase II study assessing the drug’s effects in essential thrombocythemia (ET) or polycythemia vera (PV), as well as two remaining patients in a Phase II study in multiple myeloma.
Geron said it was informed about the clinical hold by FDA verbally. The clinical hold prompted Geron to cancel a quarterly conference call with analysts scheduled for 4:30 p.m. EDT today to discuss the company’s fourth quarter and annual 2013 financial results. The company said it will report those results in its Annual Report.
FDA’s hold marks the latest clinical setback for the drug. Two years ago, Geron halted a Phase II trial of imetelstat in metastatic HER2-negative breast cancer, after results showed that the primary efficacy endpoint of median progression-free survival (PFS) in the imetelstat arm was shorter than in the comparator arm of treatment with paclitaxel. The company also declined to advance into Phase III a second Phase II trial focused on the drug candidate’s effects on non-small-cell lung cancer (NSCLC).
However, in December, the Mayo Clinic trumpeted promising early results for imetelstat, saying the first 22 of 33 patients taking the experimental drug for myelofibrosis achieved complete or partial remissions, including reversal of bone marrow fibrosis in four of the five patients. Two of the five patients with complete or partial remission also experienced complete molecular remissions.
Geron repositioned itself as a developer of first-in-class oncology drugs in 2011 and eliminated 66 full-time positions, representing 38% of its workforce at the time, after dropping its embryonic stem cell (ES) program, despite being first to go into clinical trials with an ES cell product.