The FDA has recently lifted the clinical hold on the world’s first trial of human embryonic stem cells in man. The phase I clinical trial will include patients with acute spinal cord injury. Designed to establish safety, it had been previously halted.
The FDA green light now enables Geron Corporation to move forward with the world’s first clinical trial of a human embryonic stem cell (hESC)-based therapy in man. The phase I multicentre trial is designed to establish the safety of GRNOPC1 in patients with complete American Spinal Injury Association (ASIA) impairment scale grade A subacute thoracic spinal cord injuries.
The FDA clinical hold was placed following results from a single preclinical animal study in which Geron observed a higher frequency of small cysts within the injury site in the spinal cord of animals injected with GRNOPC1 than had previously been noted in numerous foregoing studies. In response to those results, the company developed new markers and assays as additional release specifications for GRNOPC1. It also completed an additional confirmatory preclinical animal study to test the new markers and assays, and subsequently submitted a request to the FDA for the clinical hold to be lifted.
GRNOPC1, Geron’s lead hESC-based therapeutic candidate, contains hESC-derived oligodendrocyte progenitor cells that have demonstrated remyelinating and nerve growth stimulating properties leading to restoration of function in animal models of acute spinal cord injury (Journal of Neuroscience, Vol. 25, 2005).
“The neurosurgical community is ready to begin the clinical testing of this new approach to treating devastating spinal cord injury,” said Richard Fessler, professor of neurological surgery at the Feinberg School of Medicine at Northwestern University. “We know that demyelination is central to the pathology of the injury, and its reversal by means of injecting oligodendrocyte progenitor cells would be revolutionary for the field. If found to be safe and effective, the therapy would provide a viable treatment option for thousands of patients who suffer severe spinal cord injuries each year.”
Patients eligible for the phase I trial must have documented evidence of functionally complete spinal cord injury with a neurological level of T3 to T10 spinal segments and agree to have GRNOPC1 injected into the lesion sites between seven and 14 days after injury.
Although the primary endpoint of the trial is safety, the protocol includes secondary endpoints to assess efficacy, such as improved neuromuscular control or sensation in the trunk or lower extremities.
Geron has said that once safety in this patient population has been established, it plans to seek FDA approval to extend the study to increase the dose of GRNOPC1, enrol subjects with complete cervical injuries and expand the trial to include patients with severe incomplete (ASIA Impairment Scale grade B or C) injuries to enable access to the therapy for as broad a population of severe spinal cord-injured patients as is medically appropriate.
Geron has selected up to seven USA medical centres as candidates to participate in this study and in planned protocol extensions. The sites will be identified as they come online and are ready to enrol subjects into the study.
In addition to spinal cord injury, GRNOPC1 may have therapeutic utility for other central nervous system indications. Geron has established a number of collaborations with academic groups to test GRNOPC1 in selected animal models of human disease for which there is a strong rationale for the approach.
“We are pleased with the FDA’s decision to allow our planned clinical trial of GRNOPC1 in spinal cord injury to proceed,” said Thomas B Okarma, Geron’s president and CEO. “Our goals for the application of GRNOPC1 in subacute spinal cord injury are unchanged. Additionally, we are now formally exploring the utility of GRNOPC1 in other degenerative CNS disorders including Alzheimer’s, multiple sclerosis and Canavan disease,” he said.