FDA Places Geron's Imetelstat On Clinical Hold Due To Hepatotoxicity
By Cyndi Root
Geron Corporation announced in a press release that the Food and Drug Administration (FDA) has placed imetelstat on clinical hold. The Investigational New Drug (IND) application is held up while the FDA reviews safety data, especially indications that the drug may cause hepatotoxicity, or liver damage. Imetelstat treats myelofibrosis. No new patients may be enrolled in current or further studies. Current patients have to demonstrate a clinical benefit from the drug in order to continue. Dr. Ayalew Tefferim of the Mayo Clinic in Rochester, Minnesota and lead investigator, has said that he plans to seek release of the clinical hold.
Myelofibrosis
Myelofibrosis is a bone marrow disease, and among a group of disorders called myeloproliferative disorders. Leukemia is one type of myelofibrosis, caused when cancer develops in blood-forming tissues. Abnormal blood cell production can cause bone marrow scarring, enlarged liver and spleen, anemia, and fatigue. The disease is progressive, getting worse with time, and some develop more serious forms. Treatment is symptom focused.
Imetelstat
Imetelstat is a telomerase inhibitor. Telomerase activity is a high value drug target because cancer has shorter telomeres than normal cells and they are more active. Imetelstat is a modified oligonucleotide and a potent inhibitor of telomerase. Its formulation uses proprietary nucleic acid chemistry with a thio-phosphoramidate backbone, which provides tissue and plasma stability and improved binding capacity.
FDA Notice
The FDA provided written notice to Geron of the clinical hold. The federal agency said that safety concerns spurred the actions. Specifically, the FDA said that clinical trials show signs of hepatotoxicity, which may or may not be reversible. The agency provided Geron and Dr. Tefferim a way to resolve the hold, by providing the FDA with data on reversibility in all patients. Patients who did not show toxicity must be tested thirty days after the last dose. Patients who did show signs of toxicity must be tested until liver function tests (LFTs) prove normal.
Geron is further directed to suspend ongoing clinical trials and to stop pursuing additional trials. The company paused a Phase II trial, suspending treatment for ten people with thrombocythemia, polycythemia vera, and multiple myeloma. Imetelstat is Geron’s leading drug, therefore the company is not likely to abandon it. Additionally, it is a drug that does not just treat the symptoms, it may be able to treat the disease.