“An ounce of action is worth a ton of theory.”
Ralph Waldo Emerson
Last week, we transplanted the first patient in our Phase II trial for ALS. I have written before about the Phase I trial. The Phase II trial is in many ways even more groundbreaking than the first (and that is saying a great deal).
To understand the true import of the Phase II trial, it is important to understand what we are trying to accomplish. We aim to make substantial progress with this trial in three areas that will be essential in pushing the cell therapy to a Phase III trial where we hope to show efficacy in a statistically powered trial.
First, Phase II trials are about dosing. They are still about safety and a more focused look at possible efficacy, but we look at all of this through the lens of dosing. In order to get to a trial which is “powered,” or big enough statistically to demonstrate efficacy, we need to first establish the maximum safe tolerated dose of our therapy. That will be the dose that everyone in that “powered” trial will receive.
We believe that dose will consist of 20 lumbar injections and 20 cervical injections with 400,000 cells per injection. The Phase II trial we have just started is meant to “dose up” to those numbers to show that both the increased number of injections and the increased number of cells is safe. By comparison, patients in the first trial received 5, 10 or 15 injections, all with 100,000 cells per injection. Also, no patient received more than 5 injections in the cervical region. We are focused on the cervical regions in this trial because we believe that by preserving and enhancing the breathing function, we can bring the strongest benefit to our patients. It is the best way to extend their lives and improve the quality of their lives. The cervical region of the spinal cord contains the segments that control the diaphragm and breathing.
To understand why increasing the number of injections and the number of cells is crucial, remember that we believe neuroprotection of the remaining motor neurons, and even “nursing” some sick cells back to health, is what is providing the benefit to patients. The more area we can cover with cells, the more we can save.
The second big change from the first trial will be the pace of the Phase II trial. We hope to transplant each cohort of three patients in one month periods with a month of observation in between cohorts. This should enable us to complete all of the surgeries in well under a year. Again this compares to the roughly three-year period it took to complete the first trial. This schedule is the result of the FDA’s willingness to work with us to understand the data from our first trial and their desire to help move this groundbreaking trial along without sacrificing quality or the world class diligence which has made FDA-approved trials the gold standard for the world. I know there is a great deal of discussion in the orphan disease community about the FDA’s attitude towards trials for rare diseases, but they have stepped up in our case and I believe we are all on the same page now.
The third crucial element we will demonstrate with this trial involves the ability to actually deliver the therapy to such a large patient population. In addition to Emory University, patients will be treated at the University of Michigan; and most likely Massachusetts General Hospital will be added as a third site (we are still in discussions, but both of us agree that it is likely to happen). These will be the first times that anyone other than Nick Boulis has administered the therapy. We need to show that there is nothing “unique” about his technique or skills (no offense Nick) and that neurosurgeons everywhere can routinely perform the surgery. To conduct a powered trial to demonstrate efficacy, we will need to expand to multiple centers, perhaps in and out of the United States to accommodate a much larger number of patients.
Inside of Neuralstem, moving to three surgeries per month and multiple centers seems like “warp speed” as we deal with all that that entails. That being said, we understand that to a patient population that has no time to spare, it is not fast enough. But as Eva Feldman would say, “progress” indeed. As always, we are working as fast and as hard as we can to get there.
Blog originally published at Neuralstem.com