The US Food and Drug Administration (FDA) has removed the partial clinical hold on the investigator-sponsored trial of imetelstat in myelofibrosis, which the agency imposed in March.
The partial hold was placed because of a safety signal of liver toxicity in myelofibrosis patients receiving the drug.
The principal investigator of the trial, Ayalew Tefferi, MD, of Mayo Clinic in Rochester, Minnesota, provided follow-up information to the FDA regarding the reversibility of the hepatotoxicity.
Upon review of the additional data, the FDA allowed the myelofibrosis trial to proceed.
Imetelstat is a lipid-conjugated oligonucleotide that binds with high affinity to the RNA template of telomerase, thereby inhibiting telomerase activity.
Most cancers are characterized by short telomeres and a high level of telomerase activity, which makes telomerase a rational target for the treatment of cancer.
Imetelstat is also being investigated in essential thrombocythemia and other myeloid hematologic malignancies.
The trial in myelofibrosis enrolled 33 high-risk or intermediate-2 risk patients with either primary or secondary myelofibrosis. Dr Teferi presented the data at the annual meeting of the American Society of Hematology in 2013 as abstract 662.
At the time of the meeting, myelosuppression appeared to be the major dose-limiting toxicity.
Geron’s Investigational New Drug application to the FDA for imetelstat remains on full clinical hold. This affects clinical trials in essential thrombocythemia, polycythemia vera, and multiple myeloma.
