Breakthrough Therapies: Onapgo Leads the 2025 Approvals
In a significant development for Parkinson's care in 2025, the U.S. Food and Drug Administration (FDA) approved Onapgo (apomorphine hydrochloride) in February. This groundbreaking therapy is the first infusion-based apomorphine treatment for adults experiencing motor fluctuations with advanced Parkinson's disease (PD). Delivered continuously via an under-the-skin infusion device, Onapgo provides a consistent supply of medication, helping to regulate motor symptoms like tremor, stiffness, and slowness throughout the day.
Unlike traditional oral medications, which can be affected by gastrointestinal issues and irregular absorption, the continuous infusion of Onapgo bypasses the digestive tract entirely. This offers a more predictable dosing schedule and symptom control, particularly benefiting those with significant “off” times not adequately managed by existing oral drugs. The approval was supported by data from the TOLEDO study, which showed a significant reduction in daily "off" time compared to a placebo. Expected to become available in the second quarter of 2025, Onapgo represents a major step forward in managing advanced PD symptoms.
Other Notable Advances in Dopamine-Based Therapies
Beyond Onapgo, ongoing efforts aim to improve dopamine-based treatments, which remain the foundation of PD management. Other key developments from 2024 set the stage for 2025 and beyond:
- Vyalev (foscarbidopa and foslevodopa): Approved in late 2024, this portable pump delivers a continuous subcutaneous infusion of levodopa and carbidopa, similar to Onapgo but utilizing the standard PD drug. It provides consistent symptom control for advanced PD and may improve sleep quality and morning “off” times.
- Tavapadon: Expected to launch in 2025, tavapadon is a selective dopamine receptor agonist that showed promise in Phase 3 trials. Acquired by AbbVie in 2024, the drug could be used as a standalone treatment for early-stage PD or an add-on to levodopa for later stages. By targeting specific dopamine receptors, it aims to provide motor benefits with a reduced risk of side effects like compulsive behaviors associated with older, nonselective agonists.
- ND0612: This continuous levodopa/carbidopa infusion, similar to Vyalev, was resubmitted to the FDA in mid-2025 for review.
- Weekly Levodopa Injection: Australian scientists have developed a once-weekly injectable formulation of levodopa and carbidopa that could simplify treatment and improve patient compliance. Following patent filing, clinical trials are expected to move forward in 2025.
Potential Disease-Modifying Therapies in 2025 Trials
While symptomatic treatments are crucial, the ultimate goal is to slow or stop disease progression. Several investigational drugs targeting the underlying biology of PD are progressing through clinical trials in 2025.
- Prasinezumab: This drug, developed by Roche, targets the buildup of toxic alpha-synuclein protein aggregates in the brain, a hallmark of PD. In June 2025, it advanced into Phase III clinical trials, a critical step toward potential regulatory approval. If successful, prasinezumab could be one of the first disease-modifying therapies for PD.
- Ambroxol: A repurposed cough medicine, ambroxol has been found to increase the activity of the enzyme glucocerebrosidase (GCase), which helps clear alpha-synuclein aggregates. A large-scale Phase III trial (ASPro-PD) is anticipated to begin recruitment in early 2025 to test its efficacy in slowing motor progression, particularly in patients with a specific gene mutation (GBA) linked to PD.
- Bezisterim (NE3107): A Phase II trial (SUNRISE-PD) for bezisterim was planned for early 2025, testing it as a first-line standalone therapy for newly diagnosed PD patients. Its mechanism targets neuroinflammation, which is also linked to disease progression.
Innovative Approaches: Cell Therapy and Gene Therapy
Beyond traditional drug formulations, cutting-edge biological and genetic therapies are progressing toward clinical availability.
- Bemdaneprocel: This cell-based therapy involves replacing lost dopamine-producing neurons using embryonic stem cells. After promising Phase I results, the FDA granted it a regenerative medicine advanced therapy designation, and a Phase III trial is expected to start in early 2025. This approach holds the potential to rebuild damaged neural circuits.
- AAV2-GDNF Gene Therapy: An investigational gene therapy delivers a neuroprotective growth factor (GDNF) directly to the brain via a viral vector. A Phase 2 trial is underway in 2025 to evaluate its potential to stimulate nerve survival.
- iPSC-derived Dopaminergic Progenitors: A Phase I/II trial is ongoing at the University of California San Diego, using a patient's own induced pluripotent stem cells (iPSCs) to generate and transplant new dopamine cells.
Comparison of Novel Infusion Therapies for Advanced PD
| Feature | Onapgo (apomorphine hydrochloride) | Vyalev (foscarbidopa and foslevodopa) |
|---|---|---|
| Mechanism | Dopamine agonist; mimics dopamine to stimulate receptors | Dopamine precursor; delivers levodopa/carbidopa directly |
| Drug Type | Apomorphine | Levodopa/Carbidopa |
| Targeted Use | Motor fluctuations in advanced PD | Motor fluctuations in advanced PD |
| Delivery Method | Continuous subcutaneous infusion pump | Continuous subcutaneous infusion pump |
| Expected Availability | Second quarter of 2025 in the US | Approved in 2024, available in the US |
| Primary Benefit | Consistent, continuous dosing to reduce "off" time | Consistent, continuous dosing to reduce "off" time |
| FDA Approval | February 2025 | October 2024 |
| Key Differences | Apomorphine-based; potentially better tolerability profile for some infusion site reactions compared to Vyalev | Levodopa/Carbidopa-based; offers continuous delivery of the standard-of-care medication |
Conclusion
While the search for a truly curative therapy for Parkinson's continues, the landscape of available and emerging treatments is evolving rapidly. The FDA approval of Onapgo in 2025 provides a new, important tool for managing the challenging motor fluctuations of advanced PD, joining other recent innovations like the Vyalev infusion system.
Looking ahead, several groundbreaking therapies are progressing through the clinical pipeline, offering hope for disease modification and more effective symptom management. Prasinezumab and ambroxol represent promising approaches to target the underlying disease pathology, while novel delivery systems and cell therapies push the boundaries of what is possible. The sustained focus on a diverse array of therapeutic strategies ensures a rich pipeline of potential new medications and technologies, including advanced diagnostic methods and surgical innovations like adaptive DBS, bringing new optimism to the Parkinson's community.
Emerging Therapeutic Approaches and Pipeline Drugs
- GLP-1 Agonists: Drugs like lixisenatide, primarily for diabetes, showed promising Phase 2 results for slowing motor progression in early PD, though side effects were noted. Research into their neuroprotective potential is ongoing.
- NLRP3 Inflammasome Inhibitors: Several compounds are in Phase 1 and 2 trials targeting neuroinflammation, with the goal of blocking inflammatory molecules linked to dopaminergic neuron loss.
- Solangepras (CVN-424): A non-dopaminergic oral molecule, Solangepras acts on GPCR6 to improve motor and cognitive functions. A Phase 3 trial is underway to assess it as a standalone monotherapy.
- Glovadalen (UCB0022): This oral medication enhances the effect of dopamine on D1 receptors, aiming to improve motor function with fewer side effects than direct agonists.
For more information on the latest Parkinson's research and clinical trials, the Parkinson's Foundation is an excellent resource: https://www.parkinson.org/.
