InBrain Pharma's device-assisted therapy, delivering dopamine directly to the brain, has shown promising results in a Phase 1/2 clinical trial (DIVE-I) for Parkinson's disease (PD). The study, presented at the 2024 International Congress of Parkinson’s Disease and Movement Disorders (MDS), suggests a novel approach to managing motor complications in PD patients. The device offers a potential alternative to existing treatments like oral medications and deep brain stimulation (DBS).
The DIVE-I trial included 12 PD patients with motor complications and was conducted in three phases: initial feasibility and safety (Phase 1), efficacy and safety evaluation (Phase 2), and a long-term follow-up, which is ongoing.
Device Function and Rationale
The device consists of a pump placed in the abdomen, under the skin, connected to a small catheter that delivers dopamine directly into the third ventricle of the brain. This method bypasses the limitations of oral dopamine administration, which cannot cross the digestive or blood-brain barrier. According to Dr. David Devos, a neurologist and pharmacologist at CHU de Lille, Lilly University, the system allows for precise, drop-by-drop infusion of dopamine, which can be adjusted via telemetry. The pump is refilled transcutaneously with a needle, a painless procedure, every one to two weeks.
Key Findings: Safety and Efficacy
Initial results from the DIVE-I trial indicate that the device is well-tolerated, and the surgical procedure is relatively straightforward, taking approximately four hours. A significant finding was the absence of dyskinesia, a common side effect of levodopa, even at high dopamine doses. The trial also demonstrated a substantial reduction in off-periods and overall medication use, with some patients experiencing a 60% reduction. A crossover trial design compared exclusive oral treatment with dopamine infusion, revealing significant efficacy based on home diaries and activity monitors.
Positioning in the PD Treatment Landscape
While still early in development, this therapy could offer a valuable option for PD patients. Dr. Devos emphasized the importance of patient choice in selecting the most suitable device-assisted therapy. Compared to external pumps, which some patients find cumbersome, this internal pump system offers a more discreet solution. While DBS is another internal option, it is a more invasive procedure with potential risks. The open-label trial results suggest that the dopamine intracerebral system may be even more effective than DBS, although these findings require confirmation in larger, controlled trials.
Next Steps: Phase 3 Trials
The next step involves conducting large, multi-center Phase 3 clinical trials to further evaluate the therapy's risk-benefit profile in a broader patient population. Discussions with the EMA and FDA are underway to ensure the Phase 3 trials meet regulatory standards, with the goal of achieving registration by 2030.
