ACTC.OB has submitted documentation and a complete response to substantively address the issues raised by the FDA in connection with their plans to initiate a Phase I/II multicenter study using embryonic stem (NYSE:ES) cell derived retinal cells to treat patients with Stargardt’s Macular Dystrophy (SMD).
In 11/09, ACT filed an Investigational New Drug (NYSE:IND) Application to commence treating patients. ACT believes the design of its product and the choice of SMD, from a safety standpoint, represents an ideal cellular product to gain early experience and knowledge about ES cell safety.
The additional details submitted to the FDA support their belief that the product would be safe and well tolerated by patients. The Company’s process for differentiating ES cells to retinal pigmented epithelial (RPE) cells is not permissive to ES cell persistence in the culture. In fact, no stem cells could be detected even when the RPE cells were spiked during culture with up to 10 percent ES cells.
“Our batch release assay has a level of detection of less than 0.0001% for ES cell contamination of RPE cell cultures,” said Robert Lanza, M.D., Chief Scientific Officer at ACT. “We can detect a single stem cell in over a million RPE cells. This is especially significant considering the small number of cells (50,000 to 200,000) to be administered into a controlled space in the eye. Stem cells can’t persist in our culture process, and therefore do not pose a risk of contamination of the final RPE cells to be transplanted.”
ACT’s animal models were designed to assess the safety of cells in the injected eyes. The response to the FDA provides additional data to address the specific concerns presented by the Agency. In addition, studies for tumorigenicity and safety/biodistribution were extended to the lifetime of the animals. The implanted RPE cells survived long-term in the eyes of animals, and no tumors formed as a consequence to the implanted cells. No other adverse findings associated with treatment with RPE cells were observed from histological or pathological evaluation of the animals.
“We observed kinetics typical for successful transplantation of the cells,” said Edmund V. Mickunas, ACT’s Vice President of Regulatory. “Histology at all time point’s revealed persistence of human cells without inflammation or immune cell infiltration; and, without tumor formation.”
“We are extremely encouraged by this product opportunity, both in terms of safety and efficacy,” said William M. Caldwell IV, ACT’s Chairman and CEO. “We did not observe any tumorigenicity or adverse abnormal findings. We believe the inherent capability of our manufacturing process to inhibit the presence of hES cells, and the fact that the level of detection in the final batch is less than one ES cell per million, support the safety of using RPE cells in a Phase I/II Clinical Trial in humans.”