MENLO PARK, Calif., August 18, 2009 – Geron Corporation announced that its IND (Investigational New Drug application) for GRNOPC1, a cell therapy for neurologically complete, subacute spinal cord injury, has been placed on clinical hold by the FDA pending the agency’s review of new nonclinical animal study data submitted by the company. A clinical hold is an order that the FDA issues to a sponsor to delay a proposed trial or to suspend an ongoing trial.
Since filing the IND, Geron has been undertaking studies to enable dose escalation of its spinal cord injury product, and has been investigating application of the product to other neurodegenerative diseases. The company has also been performing additional product characterization and conducting further animal studies. Data from this work has been submitted to the FDA. Geron will work closely with the FDA to facilitate their review of the new data and to release the clinical hold. No patients have yet been treated in this study.
August 27, 2009 – Geron Corporation today provided additional comments on the recent clinical hold on its Spinal Cord Injury IND.
As biologic therapeutics advance in clinical trials, it is common practice to optimize product characteristics, improve manufacturing efficiency and scale, and to test the product in multiple disease models. As part of these ongoing efforts at Geron with respect to GRNOPC1, various animal studies were, and continue to be, performed to characterize the product’s effects in vivo. In previous animal studies of GRNOPC1 using materials that passed release specifications, a very low frequency of injected animals developed microscopic cysts in the regenerating injury site. These cysts were non-proliferative, confined to the injury site, and had no adverse effects on the animals. No animals developed teratomas or any other ectopic structure. Cysts of much larger size appear in the spinal cord scar tissue of up to 50% of patients with spinal cord injury.
A just completed animal study showed a higher frequency of cysts, although their characteristics were similar to the cysts seen in previous studies: non-proliferative, confined to the injury site, smaller than the injury cavity and not associated with adverse clinical outcomes.
As part of our ongoing product improvement efforts, new candidate markers and assays for product release have been identified that are linked with cyst formation across all animal studies in which cysts were found. Importantly, a manufactured lot of GRNOPC1 that was assessed using these markers and assays showed no cysts in another recently concluded animal study in spinal cord injured rats.
We have submitted these data to the FDA and are in discussions with the agency to answer its questions and proceed with the clinical trial. We are committed to the optimization of all our hESC-based products as we improve the manufacturing process and identify improved product release criteria.
Geron Corporation, whose human test of a spinal-injury treatment it developed from human embryonic stem cells was placed on hold last week by federal authorities, said Thursday that the suspension was prompted by a relatively minor problem noticed in animals given the cells.
The Menlo Park company was vague about the reason for the hold when it announced Aug. 18 that the Food and Drug Administration had halted the groundbreaking test, the first of its kind involving use of the cells in people.
But in a prepared statement Thursday, Geron said the hold resulted from the discovery of cysts in some animals given the cells. Although the cysts had appeared in some earlier animal studies, they appeared with “a higher frequency” in more recent animals tests, the company said.
Despite the finding, however, Geron said the cysts were “non-proliferative, confined to the injury site and had no adverse effects on the animals.”
It added that the company found no evidence of teratomas — a kind of tumor — in the animals and that another recent test of the cells in spinal-cord injured rats resulted in no cysts. One of the major concerns some medical experts have expressed about using human embryonic stem cells on people is that the cells, which can form into any tissue type, might develop into teratomas.
“We have submitted these data to the FDA and are in discussions with the agency to answer its questions and proceed with the clinical trial,”
Geron’s statement said. The FDA has declined to comment.
In studies several years ago, Geron reported that its revolutionary spinal treatment had helped paralyzed rats walk. The company’s treatment involves turning embryonic cells into oligodendrocytes, which help nerve fibers replace myelin, a fatty insulating substance that often gets stripped away when spines are injured, inhibiting the body’s ability to transmit sensory signals.