The US FDA (Food and Drug Administration) has lifted a clinical hold on Geron’s Investigational New Drug (IND) application – the Phase I clinical trial of GRNOPC1 in patients with acute spinal cord injury may now go ahead.
GRNOPC1 is the first ever clinical trial of a human embryonic stem cell based therapy in humans. The Phase I trials aims to establish the safety of GRNOPC1 in patients with “complete” American Spinal Injury Association (ASIA) Impairment Scale grade A subacute thoracic spinal cord injuries.
Thomas B. Okarma, Ph.D., M.D., Geron’s president and CEO, said:
We are pleased with the FDA’s decision to allow our planned clinical trial of GRNOPC1 in spinal cord injury to proceed. 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. Additionally, we are now formally exploring the utility of GRNOPC1 in other degenerative CNS disorders including Alzheimer’s, multiple sclerosis and Canavan disease.
The clinical hold followed one animal study in which a higher frequency of small cysts within the injury site in the spinal cord of animals injected with GRNOPC1 were observed – a higher risk than had been documented in various foregoing studies.
Geron subsequently developed new markers and assays as additional release specifications for GRNOPC1. The company completed an additional confirmatory preclinical animal study to try out 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).
Richard Fessler, M.D., Ph.D., professor of neurological surgery at the Feinberg School of Medicine at Northwestern University, said:
The neurosurgical community is ready to begin the clinical testing of this new approach to treating devastating spinal cord injury. 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. Once safety in this patient population has been established, Geron plans to seek FDA approval to extend the study to increase the dose of GRNOPC1, enroll 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 U.S. medical centers 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 enroll subjects into the study.
Other Potential Neurological Indications for GRNOPC1 may include Alzheimer’s disease, MS (multiple sclerosis), and Canavan disease.
Source: Geron Corporation
Written by Christian Nordqvist