Two Parkinson’s disease developments this week illustrate both the promise and the pitfalls of trying to smooth out the disease’s most stubborn symptom problem, keeping medication effects consistent as the disease progresses.
In China, Jiangsu Hengrui Pharmaceuticals has advanced HRG2010, an extended-release combination of carbidopa and levodopa, through a Phase 3 trial aimed at reducing “OFF” time in patients with motor fluctuations. According to the trial record on ClinicalTrials.gov (https://clinicaltrials.gov/study/NCT06596876), the randomized, double-blind, double-dummy, active-controlled study enrolled 165 adults with Parkinson’s and compared the new formulation against sustained-release carbidopa/levodopa. The goal was straightforward, cut down the daily stretches when medication wears off and symptoms return, while also tracking safety and motor control. More than 50 years after levodopa’s introduction, it remains the most effective drug for Parkinson’s motor symptoms, and Hengrui’s effort reflects a broader push in the field to refine how the drug is delivered rather than replace it.
At the same time, a new real-world study published August 22 in npj Parkinson’s Disease (https://doi.org/10.1038/s41531-026-01546-x) raises a caution about a different levodopa delivery method already in use, continuous subcutaneous foslevodopa/foscarbidopa infusion, administered around the clock through a portable pump. Researchers, led by J.S. Siuda, J. Malkiewicz and M. Toś, reviewed records from 198 patients treated at six tertiary movement disorder centers in Poland and found that 57 of them, nearly 29 percent, developed psychotic symptoms, defined as delusions or formed hallucinations, after starting the infusion. In 16 patients, about 8 percent of the group, those symptoms were severe enough to stop treatment altogether. That rate, the authors note, is higher than what controlled clinical trials had previously reported.
The clearest predictor to emerge from the data was a patient’s own psychiatric history. Those who had experienced psychosis at any earlier point in their disease course had nearly seven times the odds of developing it again after starting the infusion, an odds ratio of 6.89, with a 95 percent confidence interval of 2.76 to 17.15. It was the only factor that held up as statistically significant once researchers ran their full regression analysis, leading them to recommend that patients with a prior history of psychosis be selected carefully and monitored closely if they pursue this therapy.
The study comes with real limits. It was retrospective and observational, meaning researchers looked back at patients who had already received treatment rather than randomly assigning them to it, so it can’t prove the infusion itself caused every case. Psychosis is already a known complication of advancing Parkinson’s, and cognitive decline and other dopaminergic medications can contribute to it as well. Patients at tertiary movement disorder centers also tend to have more advanced or complex disease than the general Parkinson’s population, which may inflate the numbers somewhat. Even so, the gap between what showed up in everyday practice and what trials had suggested is notable, since clinical trials typically enroll carefully screened patients under controlled conditions, while real-world use often includes older patients and those with psychiatric or medical histories that trials tend to exclude, which is exactly why post-approval, real-world data can surface risks that clinical development missed.
Taken together, the two developments approach the same underlying problem from different directions. HRG2010 works through an extended-release pill designed to smooth out motor fluctuations, while foslevodopa/foscarbidopa relies on continuous infusion to avoid the peaks and valleys of oral dosing. Neither is meant to slow the underlying neurodegeneration of Parkinson’s disease, both are symptomatic treatments meant to make levodopa’s benefits more dependable.
That leaves an open question that goes beyond whether either treatment reduces OFF time, does the benefit outweigh the risk for the patients who will actually use it? For HRG2010, that answer will come into focus as full Phase 3 results and regulatory filings emerge. For foslevodopa/foscarbidopa, the new Polish data suggests the answer may depend heavily on a single factor, whether a patient has faced psychosis before, and that as Parkinson’s care grows more personalized, knowing who is vulnerable to a treatment’s risks may matter as much as knowing who stands to benefit from it.
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