Positive Phase 1 Parkinson’s Trial Results of New Therapy Reported by Prothena

Prothena recently presented results from a Phase 1b clinical trial investigating a new antibody therapy for the treatment of Parkinson’s disease at the 13th​ International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) in Vienna, Austria.

The trial was an ascending dose study of a novel antibody known as PRX002/RG7935. The antibody is currently under investigation as a disease modifying treatment for Parkinson’s disease.

Parkinson’s is a neurodegenerative disease that affects an estimated 10 million people globally. The condition is progressive and is characterized by an abnormal accumulation of the protein alpha-synuclein in both the central nervous system (CNS) and peripheral nervous system.

Alpha-synuclein is a protein found in the neurons of cells and is believed to play a major role in the pathology of several neurodegenerative disorders, including Parkinson’s disease.

In healthy individuals these proteins are believed to be soluble. In patients with alpha-synuclein dysfunction, however, the protein can “misfold,” leading to accumulations and fibrils that then lead to the death of neurons.

Recent studies have indicated that these dysfunctional proteins can propagate and spread to other nearby neurons, resulting in progressive neurodegeneration.

PRX002/RG7935 is a monoclonal antibody which targets alpha-synuclein. The medication aims to slow the progress of neurodegeneration associated with protein’s accumulation and also the cell-to-cell transmission of the aggregated disease-causing protein.

The effectiveness of PRX002/RG7935 was initially demonstrated in animal models of alpha-synuclein-related disease. The antibody reduced alpha-synuclein pathology, protected synapses between neurons and led to improvements in behavioral testing.

“PRX002/RG7935 represents a promising investigational approach as a disease-modifying immunotherapy designed to target the toxic form of alpha-synuclein that accumulates in Parkinson’s disease patients,” Joseph Jankovic, MD, professor of neurology and director of the Parkinson’s Disease Center and Movement Disorders Clinic at Baylor College of Medicine, said in a press release.

The presentation, delivered by Jankovic, shows that the therapy has an acceptable safety and tolerability profile in patients, which was the primary endpoint of the Phase 1b trial. The drug was also shown to robustly reach the central nervous system and reduce the levels of free serum alpha-synuclein up to 97% after a single dose, and maintained this following two additional monthly doses. The company had previously reported favorable results.

Targeted therapies offer new treatment options because current therapies are symptomatic only and do not address the underlying cause of the disease.

“The safety, tolerability and pharmacologic properties of PRX002/RG7935 have now been demonstrated in two double-blind, placebo-controlled Phase 1 studies, which collectively enrolled 120 individuals. Based on these study results we are able to initiate a Phase 2 study with dose levels that we expect to meaningfully reduce pathogenic alpha-synuclein in the brain of patients suffering with Parkinson’s disease,” said Gene Kinney, PhD, president and CEO of Prothena.

The company is planning to begin the PASADENA Phase 2 study of PRX002/RG7935 in the second quarter of 2017, with approximately 300 patients with early Parkinson’s disease.