Newron Pharmaceuticals S.p.A. (Newron), a research and development company focussed on novel CNS and pain therapies, announced the initiation of a phase II study of its novel molecule sNN0029 in patients with Amyotrophic Lateral Sclerosis (ALS). This safety and preliminary evidence of efficacy phase II trial of sNN0029 is supported by funding from the Wellcome Trust.
sNN0029 is a recombinant human vascular endothelial growth factor (rhVEGF-165) that is administered intracerebroventricularly (ICV). Administration of sNN0029 in animal models of ALS increased survival of motor neurons that degenerate and are a leading cause of the disability and symptoms in patients with ALS. Animals with the G93A-SOD1 mutation, known to be associated with ALS in humans, who receive rhVEGF-165 survive longer and show improved muscular strength compared to controls. Based on its mechanism of action, i.e. direct and indirect effects preventing death of motor neurons, sNN0029 may represent a unique treatment opportunity for patients with ALS.
An earlier study of sNN0029 in ALS patients at doses up to and including 2 µg/day indicated in preliminary analyses evidence of significant benefit especially in patients at the highest dose on multiple efficacy measures, compared to placebo. Treatment with sNN0029 was well tolerated and many patients have received treatment for up to two years and more.
The new study will include patients with ALS who will receive 4 µg/day as a continuous treatment in a randomised, placebo-controlled double blind fashion using an implantable pump and brain catheter. The trial has been approved by Health authorities and is currently recruiting patients to clinical sites in Belgium and the Netherlands. It will enroll 18 patients who will be assessed for safety and efficacy for three months as part of this study. Multiple clinical safety and efficacy rating scales will be used in combination with biochemical analyses and neurophysiological examination. Patients will be able to receive long term treatment after the study is completed, provided they meet protocol criteria.
sNN0029 is a novel drug candidate for the treatment of Amyotrophic Lateral Sclerosis (ALS). A recombinant human Vascular Endothelial Growth Factor 165 (rhVEGF165), it is the first treatment to target motor neurons by blocking the activity of genes causing cell death. In preclinical in vivo studies, animals with a defective VEGF-gene displayed motor neuron death in parallel with muscle weakness and atrophy, pointing to the role of VEGF for motor neuron survival. In ALS model animals, VEGF treatment slowed disease progression and increased life span. sNN0029 has also been successfully tested in a three month phase I/II safety and tolerability study in ALS patients. As ALS is fatal for most patients within a few years of diagnosis, this compound has the potential to address a great unmet medical need. In February 2013, the Wellcome Trust granted an award of up to EUR 2.5 million to support a phase I/II clinical trial to evaluate the safety and efficacy of higher doses of sNN0029 in patients with ALS.