CDNF Safe in Advanced Parkinson’s, Trial Results Show

Treatment with cerebral dopamine neurotrophic factor (CDNF), developed by Herantis Pharma, was safe and well-tolerated among patients with advanced-stage Parkinson’s disease, according to topline results from a Phase1/2 clinical trial.

The therapy also showed promise in measures of dopaminergic function in some patients.

CDNF is based on a protein naturally found in the blood and cerebrospinal fluid (CSF), the liquid surrounding the brain and spinal cord. Preclinical (in-lab) studies have shown that CDNF has both neuroprotective and neurorestorative properties in dopaminergic neurons — brain cells that produce the neurotransmitter dopamine, the chemical messenger missing in people with Parkinson’s disease.

Previous proof-of-concept studies have shown that CDNF could ease motor and non-motor symptoms of Parkinson’s disease, and could act as a disease-modifying therapy.

The Phase 1/2 clinical trial (NCT03295786) is testing the safety and tolerability of CDNF in 17 patients with advanced Parkinson’s disease.

In the trial’s first part, patients were randomly assigned to receive monthly infusions of either CDNF (medium or high dose) or a placebo for six months. Because CDNF cannot be delivered as a pill or injection — since the body will not transport it to the brain — a neurosurgeon implants a drug delivery system, provided by Renishaw, in patients’ brains.

The 15 patients who completed the first part of the study joined the trial’s extension phase, in which each of them — including those previously randomized to the placebo — will receive six doses of CDNF over six months. All patients will start on a low dose, which can be increased after an independent group of experts confirms there are no safety concerns associated with the therapy.

Results from the second part of trial are expected during the third quarter.

The study’s primary goal is to assess the safety and tolerability of CDNF and its delivery device, as well as the accuracy of surgical placement of the device.

Additional goals include CDNF’s early signs of efficacy, including its effect on the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score, patient-reported outcomes, levels of different forms of alpha-synuclein in the blood and CSF and the levels of dopamine transporters (DaT) using positron-emission tomography (PET) imaging. DaT are proteins that regulate the flow of dopamine between nerve cells, and their levels are usually lower among those with Parkinson’s.

Topline results from the first part of the study now show that CDNF was safe and well tolerated. Patients who experienced serious side effects fully recovered, and these effects were considered to be unrelated to the treatment.

Certain serious side effects “were probably related to device surgery and the drug administration process,” and these steps have been improved to avoid future incidents, the company said.

In some patients, researchers observed promising responses in dopamine transporter PET imaging, which measures dopaminergic function.

“This first set of topline data provides a solid basis for the next part of the study and confirms the positive safety and tolerability profile of CDNF,” Pekka Simula, Herantis’ CEO, said in a press release.

The promising results seen in the trial’s first part have prompted plans for a future Phase 2 trial, which will assess the effects of longer treatment with CDNF in patients in an earlier stage of Parkinson’s disease. Patient enrollment is expected to begin in 2021.