Many Parkinson’s clinical trials fail to reach Phase 3, report says
Number of active trials remains stable, annual report shows
The number of active Parkinson’s disease clinical trials has remained relatively stable since 2019, but many investigational therapies — especially disease-modifying treatments intended to slow or stop disease progression — are failing to move forward from Phase 2 to Phase 3 trials, according to a report.
A wide variety of therapy types are being investigated, with a notable recent increase in treatments that target inflammation and the disease’s nonmotor symptoms, the annual report said.
The effort, now in its fifth year, is a collaboration among Cure Parkinson’s, The Michael J. Fox Foundation for Parkinson’s Research, and other research advocates. Its aim is to present an overview of the current Parkinson’s clinical trial landscape.
Simon Stott, PhD, director of research for Cure Parkinson’s, said the stability of clinical trial numbers over the last five years is “truly remarkable” given that the COVID-19 pandemic occurred during that period. “It is a testament to the participants and the researchers involved that activities were not more disrupted,” Stott said in a press release. “And Cure Parkinson’s is proud of the role we play behind the scenes.”
The report, “Parkinson’s Disease Drug Therapies in the Clinical Trial Pipeline: 2024 Update,” was published in the Journal of Parkinson’s disease.
Progress on biomarker research, diversity
“Recent progress to improve and accelerate the Parkinson’s disease … drug development pipeline has been significant,” the study’s authors wrote. “In 2023, we saw considerable advances in the development of biomarkers” for Parkinson’s, they said.
The year also “saw great strides in expanding diversity” in Parkinson’s research, they said, citing “the discovery of a genetic risk factor in the GBA1 gene specific to people of African ancestry.”
To generate the data, the scientists analyzed information from ClinicalTrials.gov, an online clinical trial registry. They looked at all studies that were active as of Jan. 31, 2024.
The number of clinical trials for Parkinson’s remained relatively stable in 2023. There were 136 trials taking place during the year, compared with 139 active trials in the prior year.
Therapies were also grouped based on whether they were disease-modifying (DMTs), which intend to change the course of disease (i.e. slowing or stopping its progression) or symptomatic, which work to make certain symptoms less bothersome but don’t change the underlying disease course.
The proportion of trials testing DMTs has generally increased over the five years the report has been tracking data, though it didn’t change much from 2022-2023 (44% vs. 45%). The remaining 56% of trials in 2023 were for symptomatic therapies.
For both disease-modifying and symptomatic treatments, the study’s authors found a wide range of therapeutic mechanisms being tested, some new and others repurposed.
The number of investigational therapies targeting inflammation about doubled from 2022 to 2023, likely because of increased understanding that inflammation is a major driver of Parkinson’s disease, the report said. The researchers said that’s “a trend which may continue in subsequent years.”
While dyskinesia, or involuntary muscle movements, were the most targeted symptom, there also appeared to be an increase in trials targeting nonmotor Parkinson’s symptoms such as cognition, depression, or psychosis, the report found.
Barriers to Phase 3 advancement
Also relevant when looking at therapy development is its stage. Phase 1 trials look mostly at safety, often in healthy volunteers, while Phase 2 studies offer safety and short-term proof-of-concept efficacy in patients. Phase 3 trials, which mainly support regulatory approvals, look at long-term safety and efficacy in larger groups of patients.
More than half of the active trials in 2023 were Phase 2 (58%), 30% were Phase 1, and 12% were Phase 3. There were only three Phase 3 clinical trials for DMTs active in 2023, down from six in 2022.
The “limited transition of DMTs from Phase 2 to the crucial Phase 3 stage,” the study’s authors said, “may be due to the limited understanding of [Parkinson’s] biology.”
Cure Parkinson’s said it’s working to improve those numbers, with initiatives such as the ACT-PD project, a multi-arm clinical trial platform designed to help accelerate DMT trials for Parkinson’s in the U.K. This would involve the assessment of multiple investigational therapies at one time with a shared placebo group, and frequent interim analyses to determine which treatments were working and warrant transition from Phase 2 to Phase 3 testing.
“It is hoped that such initiatives will not only allow more rapid testing of novel therapies, but also provide patients with more opportunity to engage with the research,” the scientists wrote in the report. “The contribution of the [Parkinson’s] community is essential, and we acknowledge the value of their commitment and involvement.”
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