For the second time this month, the FDA has intervened in a clinical trial involving Geron’s sole drug candidate imetelstat. This time, the agency placed a partial clinical hold on an investigator-sponsored trial (IST) of the blood cancer treatment for myelofibrosis, less than three months after clinical partner Mayo Clinic trumpeted promising early results of complete and partial remissions.
The partial hold blocks Gerno from enrolling additional patients into the Myelofibrosis IST, while patients currently enrolled must demonstrate that they are deriving clinical benefit in order to continue taking imetelstat, a first-in-class telomerase inhibitor.
The company said FDA issued written notice to the study’s lead investigator, Mayo Clinic hematologist Ayalew Tefferi, M.D., citing the presence of a safety signal for hepatoxicity: “It is not known if that hepatoxicity is reversible.” FDA directed Dr. Tefferi to provide the agency with follow-up information regarding reversibility of hepatotoxicity for all patients who received imetelstat in the Myelofibrosis IST.
The investigator must follow-up liver function tests (LFTs) until 30 days from the last imetelstat dose for patients who did not experience any abnormality in earlier LFTs—and until resolution to baseline or normal range for at least two consecutive determinations for patients who experienced any abnormality.
“Dr. Tefferi has informed Geron that he plans to work diligently to seek release of the partial clinical hold,” the company said in a statement. “The investigator has agreed to provide to the FDA specific criteria he will use to determine which patients will continue imetelstat treatment in the Myelofibrosis IST.”
Geron added: “Mayo Clinic informed Geron in January 2014 that the Myelofibrosis IST had ceased enrolling new patients, and did not cite any safety concerns as the basis for that decision.”
Just a month earlier in December 2013, Mayo announced that the first 22 of 33 patients taking imetelstat 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 after taking the experimental drug.
On March 12, Geron acknowledged that FDA placed a full clinical hold on a Phase II trial assessing the drug’s effects in essential thrombocythemia (ET) or polycythemia vera (PV). The hold affected eight remaining patients in that study, as well as two remaining patients in a Phase II study in multiple myeloma.
Geron said it expects to offer an update on the earlier full clinical hold when it holds its conference call with analysts to discuss first-quarter results. The call has yet to be scheduled.
Imetelstat was the subject of a failed Phase II trial in metastatic HER2-negative breast cancer, and a Phase II trial of the drug for non-small cell lung cancer (NSCLC) that was not advanced into Phase III.
