“He that will not apply new remedies, must expect new evils..” - Sir Francis Bacon (1597)
First, the IND itself is a massive undertaking, and a complex document. It has sections which outline the history of treatment of the disease we are attacking, and gives the scientific rationale for our approach. This includes an overview of much of the literature in the field, as well of course as all of our animal and lab experiments. The basic point of all of the pre clinical work is to show a proof of principal that our cells are safe, and that there is a sound scientific basis for believing that they could provide a benefit to human patients.
Other sections of the IND deal with the manufacture of the cells under cGMP conditions. This concerns the super clean room conditions that the FDA requires for the manufacture of any therapy that is going in to humans, a demanding and exacting processes.
Further sections deal with the clinical protocol for the trial; inclusion and exclusion criteria that determine who the patients will be and sections on what we expect to “measure” to determine how the patients are doing. There are even sections on how one measures what one measures. All these things and more must be explained in detail, and justified. Then there is a section that deals with the surgical protocol. No one has ever proposed multiple injections directly into the spinal cord grey matter of patients to treat a disease like this before. In fact, almost everything in our application is novel in some way or shape. Fortunately our clinical and surgical protocols have been shaped by the absolute best ALS clinicians in the country, as well as the top neuro and spine surgeons in the country. While the stem cell science has been developed by Neuralstem, the medical side of this IND filing is the creation of a virtual who’s who of ALS clinicans and neurosurgeons, and we owe them all a great debt of gratitude. Indeed, one of the most remarkable things about this process has been to watch the fusion of the science and the medical communities as they worked to fashion this trial.
Many of you have written and/or called asking about how someone can get into the trial. We can not, of course, do anything which even hints at recruiting for a trial until and unless it is first approved by the FDA. And even then, Neuralstem will not actually be involved in the recruitment. But we hope soon to have an informational site up and running that can be accessed from our web site.
Still more of you have written or called with questions about current treatments and their possible effect on eligibility to be in our proposed trial. Here I want to be very, very clear. No one should change any plans for treatment based upon our potential trial. I will repeat myself, no one should even think about taking our potential trial into consideration when planning their disease management with their families or physicians. The first trial, even if approved exactly as we propose, will have only 15 patients, and those 15 will be comprised of five groups of 3 each. And each group of three represents a separate “point” in the disease progression. Since we hope to treat patients in all phases of the disease, it is important that we demonstrate safety in patients in each of these phases.
Like almost all first trials, ours is designed primarily to test the safety of both the cells and the surgical route of administration. We have also proposed secondary endpoints where we will be measuring efficacy. As I have said to all of those who have written, we know this is not the pace you want to see, but we are working as hard and as fast as we can.
Finally, many of you have asked about the FDA process, in particular, how long will it take to get approval for the trial? Technically, the FDA is required to get back to us in 30 days, however their response can range from, “go ahead” to “wait, we have some questions” to, “we see serious problems, here is what we want to know”. Obviously we would not have submitted this IND if we didn’t believe that there was a compelling case to move forward. But as I said, almost everything we are doing is novel and I am sure that there will be questions. What I can tell you, is that we feel we have very good answers to the questions, and we hope for a speedy process. It is however, a process. I have said publicly that we hope to start the trial this spring, and I still think that is a good estimate.
As I spend more and more time with the ALS patient and treatment community, I am continually amazed and impressed by the courage, compassion and strength of the patients and those involved in their care. It is akin to what one finds in the pediatric brain tumor community, with which I have a personal history. It is both inspiring and humbling. We bring what we all hope is indeed a new remedy to the fight. And we are excited, and proud to be here.
A happy and grateful holiday to all.
Richard Garr
Neuralstem President & CEO