Why Cethrin for spinal cord injury?
Cethrin™ is BioAxone’s lead protein compound that has completed a Phase 2a study in patients with spinal injury. BioAxone is currently planning further clinical studies in acute spinal cord injury. This study is not yet recruiting.
Cethrin has the following attributes:
- Cethrin is a pro-regenerative drug that stimulates damaged axons to regrow
- Cethrin is neuroprotective and reduces tissue loss after neurotrauma
- Cethrin is a custom-designed fusion protein derived from a natural product
- Cethrin can be delivered by a safe and non-invasive method
- Cethrin’s break-down products are amino acids, the building block of proteins, and therefore long-term toxicities are less of a concern than with chemical drugs.
We focused on Cethrin as the best investigational candidate because of very positive results in our preclinical studies. Immediately after injury is the most important time to limit damage and start repair. The spinal cord is vulnerable to secondary consequences of injury that include axon degeneration and cell death. Cethrin is the only drug in development for the acute care period the first week after injury. It is applied during surgery, and approximately 90 percent of acute spinal cord injury patients will have surgery to decompress the spinal cord within the first week after SCI.
Today there are many other types of treatments in development for neurotrauma, including cell based therapies. Studies in animals suggest that multiple treatments will enhance recovery, but from a translational drug development standpoint, the fastest way to get treatments to patients is to show safety and efficacy for individual therapeutics before experimenting with combinations.
At BioAxone BioSciences, we believe that the future for effective treatment of spinal cord injury will be a continuum of care along the road to recovery, starting with Cethrin and then followed with other treatments and aggressive rehabilitation. With early Cethrin treatment in spinal cord injury, we anticipate it will help axons respond to other repair strategies. While it is somewhat arbitrary to define acute and chronic phases of spinal cord injury, we believe that Cethrin will also be part of future combinations designed to treat chronic spinal cord injuries.
BioAxone’s studies are paving the way to help patients with spinal cord injury. Importantly, Cethrin’s mechanism of action is well understood and Cethrin is poised to be the first drug available to patients that promotes axon regeneration as part of the recovery process.
How Cethrin works:
Cethrin is applied by a surgeon
Before application, Cethrin is mixed with an approved fibrin sealant that is to be deposited directly at the site of injury, without injection into the spinal cord itself. The mixture rapidly solidifies into a semi-rigid gel, and the gradual dissolution of the gel sustains release, allowing Cethrin to continue to infiltrate the region of the injury after it has been applied. Cethrin’s transport sequence allows the drug to penetrate tissue and cells where it reverses damaging cellular responses. Cethrin’s enzymatic activity acts on the protein Rho, one of the master control proteins for axon regeneration. Inactivation of Rho promotes both regeneration and survival of injured neurons. These activities help reduce damage and promote repair after neurotrauma.
BioAxone’s preclinical research in various types of animal models has shown Cethrin’s potential to repair damage after SCI. Axon regeneration has been demonstrated in both rat and mouse spinal cord, as well as traumatic optic nerve injury. Cethrin reduces the extent of tissue damage in contused spinal cord, and has been shown to be neuroprotective (it reduces death of neurons) not only in injured spinal cord, but also in retinal models where precise cell counts are possible.
Clinical studies to date.
Cethrin has been tested in a Phase 1/2a clinical trial designed to test safety and tolerability. The study was an open-label dose ranging study in 48 patients with acute spinal injury in a multi-centered trial. Cethrin had a good safety profile at all of the doses tested (0.3 mg, 1 mg, 3 mg, 6 mg, and 9 mg). In the cervical patient cohorts, the improvement in ASIA motor score observed at the most effective dose (3 mg) at 12 months was over twice what would have been expected in untreated patients (27 motor points versus 10 expected).