• “An invasion of armies can be resisted, but not an idea whose time has come.”

Posted April 2, 2012

“An invasion of armies can be resisted, but not an idea whose time has come.”
- Victor Hugo

The FDA has approved Neuralstem moving on to the cervical region injection phase of our ALS trial, and we have successfully transplanted two of the three patients in the initial cervical cohort, with the third scheduled for later this month. These first three patients in this cervical phase each received, or are scheduled to receive, five injections of neural stem cells in the upper spinal cord, or cervical, region. These segments ultimately control the breathing function. It is here that we believe we can really help ALS patients. It is here that we have the best chance of not only prolonging their lives, but also significantly improving the quality of their lives. Almost all ALS patients reach a stage where they need mechanical help to breath before they die. Our goal is to keep that from happening.

Our experience with the first 12 patients in this trial (all of whom received only lumbar-area injections) has certainly raised expectations. We have demonstrated the safety and feasibility of intraspinal injections with our cells. We believe that this is the only way to put the cells where they “need” to be. We have seen encouraging signs of stability in breathing, and of course one patient who has “gone public” has shown marked improvement in many functional tests. He recently celebrated the one year anniversary of his surgery. The patients are only receiving (roughly) 25% of the cells that we want to include in each injection, and only 25% or 50% of the number of injections that we ultimately would like to administer to each patient. Given all of this, some have asked why the pace of the trial is so slow?

It is essential that therapies be developed under a process, such as the FDA approval process, which insures that they are safe and effective before offering them to the public. The FDA’s process is generally acknowledged to be the “gold standard” of the world for such approvals. There are times, however, when the pace dictated by this process seems at odds with everyone’s best interests and intentions. Indeed, I believe that the Agency itself feels handcuffed by their statutory mission and structure at times. There are several proposals now being floated on the Hill to try to change this. I wrote recently about The TREAT Act introduced in the Senate that focused on trying to find a way to allow for experimental treatments to move through this process with more speed, but no less stringent a review of efficacy. Another (bipartisan) bill has been introduced (called the Advanced Breakthrough Therapies for Patients Act) which takes yet a different approach towards changing the FDA’s outlook and behavior. Both of these Acts attempt to give the FDA some statutory tools to move faster and require smaller or fewer trials when dealing with serious or life-threatening diseases, and both try to change the FDA’s “culture” by statutorily amending their mission to include supporting and enabling innovation and new therapies. The FDA’s User Fee/funding act expires at the end of September and it is considered “must pass” legislation by both sides. This means that amendments to the bill actually have a chance of being included in a law that will actually be passed. It is to be hoped that some or all of this language will make it into the final bill.

More importantly, these efforts are the product of a tremendous outreach effort by patient advocacy groups and industry groups alike; all frustrated with the ever-increasing time and money that it takes to move new therapies through the FDA approval process. They are all well thought out, workable solutions. They are ideas. None however go to the heart of the matter like the idea proposed by former FDA commissioner Andy von Eschenbach in February. The former commissioner proposed that the FDA approve drugs based on safety alone, and “leave efficacy testing for post-market studies.” This idea, presented in an op-ed in The Wall Street Journal, is absolutely brilliant. For fatal and/or untreatable diseases this is exactly the right approach to take. Let the FDA do what it does best: insure quality and safety; and then allow patients access to these experimental drugs for diseases (such as ALS) where there are no therapies, and there is nothing on the market that can help them.

This is not one of the proposals that may actually make it into the bill, but it is something to keep in mind. It is so radical, that it will require a good deal of thought and vetting in the treatment community before it can become proposed law. But that vetting will happen. The very idea that a former FDA commissioner could propose such an idea shows that, with every passing day, the momentum is building to find new ways to create faster and broader access to medicines for patients who desperately need them.

Back in the day-to-day world: Neuralstem is in discussions with the FDA to find a way to accelerate the pace of our ALS trial by increasing the dosing in the remaining Phase I patients. I believe, working together, we will find a way. But the FDA can only act within its existing structure, culture, and regulatory framework. What is really needed, of course, are new structures, a new culture, and a new regulatory framework that will enable innovation and bring the promise of a new generation of science to patients. All of the Acts and ideas mentioned above provide movement in that direction. Allowing for quicker and broader access to treatments for fatal and/or incurable diseases is an idea whose time has come. It is inevitable.