First Parkinson’s patient dosed in Phase 2/3 clinical trial of BHV-8000
Brain-penetrant oral small molecule aims to slow decline in function
The first patient has been dosed in a pivotal Phase 2/3 clinical trial testing BHV-8000, a brain-penetrant oral small molecule that Biohaven Therapeutics is developing as a disease-modifying therapy for neuroinflammatory conditions, including Parkinson’s disease.
The clinical trial (NCT06976268) is evaluating the effectiveness and safety of BHV-8000 in individuals with early Parkinson’s disease. Specifically, it aims to determine whether daily doses of 10 mg or 20 mg of BHV-8000, taken for up to nearly one year, can slow functional decline compared with a placebo.
The trial is recruiting up to 550 patients, ages 40 to 85, who have been diagnosed with idiopathic Parkinson’s — meaning the cause of the disease is unknown. Recruiting is ongoing at a single location in Florida, with other locations expected to open elsewhere, including in the U.S., Canada, and some European countries.
“We are proud to announce the initiation of our pivotal clinical trial in early Parkinson’s disease for BHV-8000, a novel therapy with broad potential for treating neuroinflammatory and neurodegenerative diseases,” Pete Ackerman, MD, Biohaven’s senior vice president of clinical development, said in a company press release.
BHV-8000 designed to block proteins regulating immune responses
In Parkinson’s disease, the loss of dopaminergic neurons — brain cells that produce dopamine, a key signaling molecule for motor control — leads to a range of motor symptoms, including tremors, slowed movement, muscle stiffness, and balance difficulties.
The immune system is thought to sustain a cycle of long-lasting inflammation that contributes to the loss of dopaminergic neurons, driving disease progression. Over time, this interferes with daily activities. While treatments can ease symptoms, no therapy to date can slow or stop the disease’s progression.
BHV-8000 is designed to inhibit TYK2 and JAK1, two proteins involved in regulating immune responses throughout the body, including neuroinflammatory processes in the brain and spinal cord. In Parkinson’s, dysregulated immune signaling, potentially involving TYK2 and JAK1, may contribute to chronic neuroinflammation. Inhibiting these two proteins may help control long-lasting inflammation, slowing or stopping Parkinson’s progression.
“There are currently no available disease-modifying therapies to treat Parkinson’s,” Ackerman said, yet the number of patients diagnosed with the disease is expected to double by 2050. “As a brain-penetrant, selective inhibitor of TYK2 and JAK1, BHV-8000 has the potential to modulate critical inflammatory pathways.”
Parkinson’s clinical trial to test 2 therapy doses over nearly 1 year
In Phase 1 clinical testing of 58 healthy adults, BHV-8000 was found safe and well tolerated when given as single or multiple daily oral doses. BHV-8000 entered the brain and maintained levels high enough to inhibit at least half of TYK2 and JAK1 activity. Compared with a placebo, it also led to significant reductions in blood biomarkers of inflammation.
Patients in the Phase 2/3 clinical trial will be randomly assigned to take either BHV-8000 — at a dose of 10mg or 20 mg — or a placebo once daily for up to 48 weeks. To be eligible, patients must not have taken any Parkinson’s medications in the past three months or for more than 28 days (about one month) in total.
We look forward to working closely with the global Parkinson’s community and regulatory agencies … as we strive to deliver a transformative therapy where none currently exists.
The primary objective of the study is to compare the time to a prespecified worsening event on Part II of the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), which assesses patients’ ability to carry out daily activities like eating and dressing. This type of analysis has been accepted by the U.S. Food and Drug Administration (FDA), according to Biohaven.
“We look forward to working closely with the global Parkinson’s community and regulatory agencies, including the FDA, who provided key input on the study’s time-to-event endpoint, as we strive to deliver a transformative therapy where none currently exists,” Ackerman said.
Secondary goals include watching for changes in MDS-UPDRS Part III scores that measure the severity of motor symptoms, and in the Clinical Global Impression of Severity and Parkinson’s Disease Composite Score – Function scores, which measure how well a person can carry out daily activities. The researchers will also look at dopamine transporter scans to check for the loss of dopaminergic neurons.
“We are delighted to begin enrollment in this trial for people living with Parkinson’s,” said Stuart Isaacson, MD, who directs the Parkinson’s Disease and Movement Disorders Center of Boca Raton and is the trial’s principal investigator. Isaacson is also medical director of the Parkinson’s Research and Education Foundation.
About the Author
