Ted Harada became something of a mini celebrity back in March 2011 when he became the final patient of 15 in a phase I trial for NSI-566, Neuralstem's (CUR) flagship experimental ALS stem cell treatment. His ALS was temporarily beaten back not once, but twice, with two sets of injections, the second of which occurred last August. As of late, it seems he has developed a sort of religious fire to push the FDA to allow Neuralstem to move on to phase II already and to take it easy on companies in general looking to push through the ALS clinical pipeline.
Wrote Richard Garr, President and CEO of Neuralstem:
Ted Harada stood up and excoriated the FDA for slowing down a trial and a therapy that held enormous potential for ALS patients. 'Just look at me,' he said, in more than words. In his testimony, Ted proposed that it is time that the FDA did the right thing and treat this process with the same urgency that the ALS community feels. He spoke with passion, elegance and conviction.
Harada was speaking at a public hearing called by the FDA for the ALS community to voice its opinions and concerns about how to proceed with ALS clinical research. Such FDA public relations meetings are not an every day occurrence, and may signal an easing of policy when it comes to experimental treatments like NSI-566.
Nobody is sure what the catalyst was that inspired the FDA to call such a meeting just to get yelled at. They had to know they'd be taking some heat and plenty of heart-wrenching begging from enormously suffering people. So why subject themselves to that? Garr theorizes that it may have something to do with the recent failure of Biogen Idec's (BIIB) dexpramipexole phase III trial. 'Dex' as it was called, wasn't just a failure. As the largest ALS phase III trial ever to have been conducted at 943 patients, it was a spectacular failure. There are only about 20,000 people in the entire United States that suffer from ALS according to FDA estimates, so finding 943 of them who are able and willing to participate in a clinical trial is not like finding 943 with the common cold testing out the latest analgesic. This trial was conducted using 5% of the entire subset of the US ALS population. Its failure, speculates Garr, has induced an internal crisis in the ALS community, so the FDA called a meeting. It took place on February 25, and transcripts will be available at regulations.gov by mid-April.
If this is indeed a sign that the FDA is softening its approach to ALS clinical trials, then progress already made could quicken in the coming years.
ALS Progress so far very encouraging
The present clinical layout shows two companies that look to be making serious progress on ALS so far. One as mentioned is Neuralstem, the other Brainstorm (BCLI.OB), an Israeli company. Each has its own prototype patient whose ALS has been beaten back. Neuralstem has Harada, and Brainstorm has Rabbi Refael Shmulevitz. The two companies' technologies are similar, with Neuralstem using an embryonic stem cell line, and Brainstorm using a system it calls NurOwn, where adult stem cells are taken from a patient's own bone marrow and used to create nerve cells.
In terms of the clinical race, Brainstorm has begun a phase IIa trial authorized by Israel's health ministry, though it is unclear where that trial stands with the FDA or if Israeli's health ministry has any leverage with its sister bureaucracy in the US. In any case, the first patient in that trial was treated at the beginning of last month. Brainstorm's trial will involve only 12 patients, all of whom have already been recruited, though at such a small sample it is more like a phase I. Then again, numbers of patients with ALS are extremely limited, especially in Israel where the trial is being conducted.
Meanwhile, Neuralstem just had another phase I trial approved, also for NSI-566, but this one for spinal cord injury (SCI), a substantially higher subset of patients. According to the Christopher & Dana Reeve Foundation, there were approximately 840,000 people living with chronic SCI
Neuralstem's phase II is being held up by the FDA at the moment, with considerable frustration being expressed at last month's public hearing. Even so, Neuralstem was able to secure funding from the National Institute of Health (NIH) for most of the expenses of its upcoming phase II trial, which will both help move it along and keep Neuralstem's finances strong for now.
Neuralstem's balance sheet was recapitalized last quarter giving it close to $10M in cash. With a very low cash burn rate of about $2.5M per quarter, the current window is about a year, or perhaps slightly longer given that the NIH has offered to fund phase II, and that Neuralstem does in fact have a small but steady income stream from licensing out its stem cell technologies.
I am very curious to read those upcoming transcripts out of last month's parlor meeting to see if they show any hints as to the direction the FDA will take. Rather than being in competition with each other, I believe Neuralstem and Brainstorm have much more to gain from the other's success. Say, if this first phase II patient in Israel begins to show signs of improvement, Neuralstem will have more ammunition it can use to pound the table and demand to move forward with its own trials.
There is only one FDA approved medication for ALS, and that Sanofi's (SNY) Rilutek, which at best extends life 3-5 months before ALS suffocates its victims. So the market is still wide open for these two companies to show their stuff.