The US Food and Drug Administration (FDA) has granted clearance to Asterias Biotherapeutics Inc. to initiate a phase 1/2a clinical trial of its product, AST-OPC1, in patients with complete cervical spinal cord injury.  The approved trial follows the successful completion of the phase 1 clinical study of the product, and is designed to assess safety and activity of escalating doses of AST-OPC1 in patients with complete cervical spinal cord injuries, the first targeted indication for AST-OPC1 and the first of future product registration clinical trials.

"We would like to acknowledge the scientists, clinical investigators, and FDA for working with us to develop AST-OPC1," stated Pedro Lichtinger, president and CEO of Asterias.  "We are especially enthusiastic about working with our new partner, CIRM, in executing this clinical trial. The FDA clearance provides Asterias with imminent access to the previously announced $14.3 million CIRM grant, which provides non-dilutive funding to support both the clinical trial and other product development activities for AST-OPC1."

AST-OPC1 is a population of cells derived from human embryonic stem cells (hESCs) that contains oligodendrocyte progenitor cells (OPCs). OPCs and oligodendrocytes perform supportive functions for nerve cells in the central nervous system. The foundation for this newly cleared phase 1/2a clinical trial comes from results from the phase 1 clinical trial of AST-OPC1, which met its primary endpoints of safety and feasibility when administered to five patients with neurologically-complete, thoracic spinal cord injury. These five patients were administered a low dose of two million AST-OPC1 cells and have been followed to date for 2 to 3 years. No serious adverse events were observed associated with the delivery of the cells, the cells themselves, or the short-course immunosuppression regimen used.  There was no evidence of expanding masses, expanding cysts, infections, cerebrospinal fluid leaks, increased inflammation, neural tissue deterioration or immune responses targeting AST-OPC1 in these patients.  In four of the five subjects, serial MRI scans performed throughout the 2 to 3 year follow-up period indicate that reduced spinal cord cavitation may have occurred and that AST-OPC1 may have had some positive effects in reducing spinal cord tissue deterioration.

The new phase 1/2a clinical trial will be an open-label, single-arm study testing three escalating doses of AST-OPC1 in 13 patients with subacute, C5-C7, neurologically-complete cervical spinal cord injury. These individuals have essentially lost all sensation and movement below their injury site with severe paralysis of the upper and lower limbs. AST-OPC1 will be administered 14 to 30 days post-injury. Patients will be followed by neurological exams to assess the safety and activity of the product.  Selection of the clinical trial sites is well underway and the company expects to begin patient enrollment during the first quarter of 2015.

The new clinical trial differs from the original clinical study in that doses up to 10 times higher will be tested.  In addition, the trial will focus on patients with neurologically-complete cervical spinal cord injuries.  Because of the anatomy of the spinal cord and the existence of more sensitive outcomes measures to assess movement of the arms and hands, it is currently believed that detection of efficacy is much more likely to occur in patients with cervical injuries. It is this patient population that Asterias anticipates will be the target for the first registration clinical trials of AST-OPC1. The results of the phase 1/2a clinical trial are expected to provide support for a phase 2b expansion study that will be conducted to more thoroughly demonstrate safety and efficacy of the product.

Over 12,000 individuals suffer a spinal cord injury (SCI) each year in the United States alone, and approximately 1.3 million Americans are estimated to be living with a spinal cord injury. Traumatic SCI most commonly impacts individuals in their 20s and 30s, resulting in a high-level of permanent disability in young and previously healthy individuals. Individuals with SCI not only have impaired limb function, but also suffer from a wide range of additional disabilities which can each significantly impact quality of life, and can even be life threatening in some instances. According to the National Spinal Cord Injury Statistical Center, the life expectancy of an individual suffering a cervical spinal cord injury at age 20 is 20-25 years lower than that of a similarly aged individual with no SCI.

In addition to its dramatic impact on quality of life for patients and their families, SCI is responsible for tremendous costs to society. At one year post injury, only 11.8% of SCI patients are employed, and fewer than 35% are employed even at more than twenty years post-injury. Additionally, many patients require help with activities of daily living such as feeding and bathing. As a result, the lifetime cost of care for SCI patients are enormous; a recent paper estimated lifetime costs of care for a patient sustaining a cervical SCI at age 25 at $4.2 million. Overall, it has been estimated that SCIs cost the US over $14.5 billion per year in direct medical costs and disability support, plus an additional $5.5 billion in lost productivity.

There are currently no approved therapies for the treatment of SCI, and the complex pathology of the injury is unlikely to be addressed by a traditional small molecule or protein therapeutic. AST-OPC1, an oligodendrocyte progenitor population derived from human embryonic stem cells, has been shown to have three potentially reparative functions which address the complex pathologies observed at the SCI injury site. These activities of AST-OPC1 include production of neurotrophic factors, stimulation of vascularization, and induction of remyelination of denuded axons, all of which are critical for survival, regrowth and conduction of nerve impulses through axons at the injury site. In preclinical animal testing, AST-OPC1 administration led to remyelination of axons, improved hindlimb and forelimb locomotor function, dramatic reductions in injury-related cavitation and significant preservation of myelinated axons traversing the injury site.

Asterias' core technologies center on stem cells capable of becoming all of the cell types in the human body, a property called pluripotency. Asterias plans to develop therapies based on pluripotent stem cells to treat diseases or injuries in a variety of medical fields having major unmet needs and without adequate therapies available.