Geron will be able to start what it claims is the world’s first human trial with a human embryonic stem cell (hESC)-based therapy now that FDA has lifted a nearly year-long clinical hold on the firm’s IND application for its acute spinal cord injury therapy, GRNOPC1. The Phase I trial will evaluate the hESC-derived oligodendrocyte progenitor cell therapy in patients with complete American Spinal Injury Association (ASIA) Impairment Scale grade A subacute thoracic spinal cord injuries. The primary study endpoint is safety, but additional secondary endpoints will assess efficacy of the treatment in terms of improved neuromuscular control or sensation in the trunk or lower extremities, Geron points out.
Looking forward, Geron says once the safety of GRNOPC1 has been confirmed in this first patient population it will look to increase the treatment dose, enroll additional subjects with complete cervical injuries, and expand the trial to include patients with severe incomplete injuries classified as ASIA Impairment Scale grade B or C.
“Our goals for the application of GRNOPC1 in subacute spinal cord injury are unchanged; to achieve restoration of spinal cord function by the injection of hESC-derived oligodendrocyte progenitor cells directly into the lesion site of the patient’s injured spinal cord,” states Thomas B. Okarma, M.D., Geron’s president and CEO. “Additionally, we are now formally exploring the utility of GRNOPC1 in other degenerative CNS disorders including Alzheimer’s, multiple sclerosis, and Canavan disease.”
GRNOPC1 comprises hESC-derived oligodendrocyte progenitor cells that published studies have shown demonstrate remyelinating and nerve growth stimulating properties that lead to restoration of function in animal models of acute spinal cord injury, Geron explains.
FDA placed a clinical hold on the IND for GRNOPC1 during August 2009 when it was found that in one preclinical study animals treated using GRNOPC1 developed a higher frequency of small cysts at the injury site than animals treated in previous studies. Geron subsequently developed new markers and assays as additional release specifications for the treatment and has completed a separate confirmatory preclinical animal study to test the markers and assays.
The firm’s regenerative pipeline includes GRNCM1, an hESC-derived cardiomyocyte treatment in development for the potential treatment of heart disease. The product is currently undergoing large-scale animal testing. Geron is separately developing an hESC-based islet cell therapy GRNIC1 for the treatment of diabetes and is working with collaborators on a degenerative joint disease program based on the development of hESC-derived chondrocytes. The firm says its collaborators aim to start large-scale animal studies with the treatment during 2010.