New data from NodThera’s phase 1b/2a study in patients with Parkinson disease (PD), assessing the impact of the company’s oral, brain-penetrant NLRP3 inflammasome inhibitor NT-0796, showed that the treatment reduced inflammatory and disease-specific biomarkers in the blood and cerebrospinal fluid (CSF).1 The company noted that these results suggest NT-0796 has promise as a potential long-term, oral dosing treatment in patients with PD.
In the study, findings showed mean reductions of key proinflammatory biomarkers in CSF including IL-1β, IL-6, CCL2, CXCL1 and CXCL8 with NT-0796 over 28 days compared with baseline to levels approximating those of older healthy controls. Overall, investigators noted that NT-0796 achieved delivery of antineuroinflammatory and antiinflammatory changes in 7 days and sustained these changes over a 28-day stretch among participants with PD.
Top Clinical Takeaways
- NT-0796, NodThera's NLRP3 inhibitor, demonstrates efficacy in reducing inflammatory biomarkers in patients with PD, suggesting promise as a long-term treatment.
- The observed reduction in neurodegenerative markers and acute phase biomarkers, along with favorable safety and tolerability profiles, further support NT-0796's potential in PD management.
- These findings indicate a significant advancement towards disease-modifying strategies for PD treatment, potentially halting its progression and offering hope to patients.
“Our new findings in PD, a condition with substantial unmet medical needs, are profound and highly encouraging. They bolster our confidence in the ongoing program, with phase 2 studies now in advanced planning stages. The correlation between PD and neuroinflammation is well-documented, with alpha-synuclein fibrils triggering microglial NLRP3 activation, leading to neuroinflammation and subsequent neurodegeneration,” Alan Watt, PhD, MBA, chief executive officer at NodThera, said in a statement.1
READ MORE: Short Questionnaire Accurate in Identifying Parkinson Disease-Associated Psychosis
In further findings, investigators also observed a reduction in neurodegenerative markers, including neurofilament light chain and soluble TREM, following dosing of NT-0796. In participants who had elevated acute phase biomarkers C-reactive protein (CRP) and fibrinogen, researchers reported significantly reduced levels after treatment initiation, which was consistent with the peripheral anti-inflammatory effects of NT-0796 observed in older healthy volunteers assessed in an earlier stage of the trial.
“This is the inaugural demonstration of an NLRP3 inhibitor’s potential to not only address PD but also offer a broader impact on neurodegenerative diseases. Given that existing PD treatments primarily manage symptoms, our innovative, disease-modifying strategy presents a significant shift, aiming to stop the disease progression. NT-0796’s demonstrated efficacy in reducing neuroinflammation in patients heralds a substantial advancement towards halting this devastating disease,” Watt added in the statement.1
Investigators noted that adverse events (AEs) reported were mainly mild and transient, and no serious AEs were observed with NT-0796, suggesting that the treatment is safe and tolerabile among patients with PD. In pharmacokinetic data, authors observed that concentration in CSF maintained over 24 hours with NT-0796, revealing the treatment’s potential for once-daily dosing and levels of the treatment in the brain.
