News came late last month of a new clinical trial for acute spinal cord injury. Asubio Pharmaceuticals, based in New Jersey, a small subsidiary of Daiichi Sankyo, a large Japanese pharma company, announced a 164-patient Phase II randomized, placebo-controlled trial for its molecule SUN13837
, which will be administered to persons with C4 to C7 injuries within 12 hours after injury, in U.S. and Canadian trauma centers.
The drug, injected daily for 30 days, is believed to protect fragile nerves in the damaged area of the cord by managing glutamate, which can be released in toxic amounts amidst the cascade of destruction that occurs in the hours and days after initial trauma.
From the press release:
"SUN13837 is expected to provide neuroprotection from glutamate excitotoxicity and promote axonal outgrowth, which is often inhibited after spinal cord injury," said Benjamin Levinson, M.D., Senior Director of Medical and Scientific Affairs at Asubio. "It is similar in mechanism to basic fibroblast growth factor (bFGF) but without the troublesome complication of stimulating cell proliferation. Like bFGF, SUN13837 is thought to bind with FGF receptors to induce the intracellular signaling events providing its positive properties. Unlike bFGF (a large protein), SUN13837 is a highly lipid soluble small molecule that can be easily and reliably administered through peripheral intravenous injection."
Asubio says its preclinical research for SUN13837 indicates no significant side effects – the Phase I safety data came from healthy volunteers – while test animals showed better survival of cortical spinal cord neurons and axon regrowth. Said the company, “significant and remarkable functional recovery has been observed after treatment with SUN13837.”
They’re hoping for two levels of improvement in tetraplegic patients:
"A two motor-level improvement in a mid-cervical injury can have a significant impact for improving a patient's activities of daily living, including self-care and mobility …. The potential outcome of this trial may support greater independence for patients with spinal cord injury, and help reduce demands on healthcare resources," added Dr. Levinson. "Of course, cautious optimism is needed until this and other studies have been conducted. Nonetheless, we are hopeful that SUN13837 will offer a significant advance in the treatment of this devastating, life-altering type of trauma."
Asubio has kept a very low profile in the SCI/neurotrauma world; the company presented data at a single professional meeting, that of SCI physicians (ASIA). There is no published data on the 13837 drug, although it is apparently compelling enough to convince clinicians at as many as 50 centers to participate. I contacted Asubio to find out more. On the call: the aforementioned Levinson; Robert Reed, Vice President Business Development & Strategic Planning; and Joseph Gerthner, VP Medical Affairs.
I asked if they would share the data and define “significant and remarkable functional recovery” in the preclinical animal results to justify a large and expensive trial. No. Not until results are published. Said Reed, “We’re not trying to be secretive, it’s a matter of making sure the scientists behind the work get proper credit. But we’re trying to get the drug developed in a way to help patients as quickly as possible.”
I asked about the mechanism, how the drug works. Bascially, 13837 is a bFGF analog or “mimicking agent,” said Levenson. It acts like bFGF, for which there is a good bit of literature pertaining to protecting the nervous system after trauma.
Here’s an example, from the Miami Project, from 1999: “Neuroprotective Effects of Basic Fibroblast Growth Factor Following Spinal Cord Contusion Injury in the Rat
." From the paper:
These data demonstrate that the continuous intramedullary infusion of bFGF initiated one hour after moderate contusion injury of the spinal cord significantly reduces the total zone of injury and the zone of partial preservation.
Another paper, circa 2000, from a group at the University of Kentucky: “Basic Fibroblast Growth Factor (bFGF) Enhances Functional Recovery Following Severe Spinal Cord Injury to the Rat
Alas, bFGF didn’t fare so well in stroke: A drug called Trafermin, a recombinant version of bFGF, showed great promise in animal models of stroke. Large Phase III clinical trials failed – halted midstream – as many patients got hypotensive and others died. Still, Trafermin has not been tossed away – it may not neuroprotect but it may have another longer term benefit: promoting neuronal plasticity. More stroke trials may be forthcoming.
“Neuroprotection in Experimental Stroke with Targeted Neurotrophins
,” published in 2005, tells more.
Meanwhile, Asubio doesn’t mention plasticity but hopes patients on 13837 can gain two levels of function compared to baseline. Said Reed, “There are very few options clinically for people with spinal cord injury. We believe this is an unmet medical need. And we believe we have done the proper due diligence on the safety and efficacy for our compound to move forward with our proof of concept study.”