For decades, the cornerstone of Parkinson's disease (PD) therapy has been levodopa, which replenishes the brain's dopamine supply to control motor symptoms like tremor, stiffness, and slow movement. While effective, oral levodopa can lead to motor fluctuations—periods of good symptom control ('on' time) alternating with periods of worsening symptoms ('off' time), especially as the disease progresses. To address these challenges, recent pharmacological advancements have focused on developing therapies that offer more consistent, continuous delivery of medication.
The Latest FDA-Approved Medications
Several new treatments have recently gained approval, offering improved symptom management for patients with moderate to advanced PD.
Vyalev (foscarbidopa/foslevodopa)
Approved by the FDA in October 2024, Vyalev is the first 24-hour continuous subcutaneous (under-the-skin) infusion of a levodopa-based therapy. This treatment delivers a steady flow of foscarbidopa and foslevodopa (prodrugs that convert to carbidopa and levodopa in the body) via a small, portable pump.
- How it works: By providing a continuous supply of medication, Vyalev helps smooth out the plasma levels of levodopa, which helps reduce the peaks and troughs that contribute to motor fluctuations.
- Who it's for: Adults with advanced PD who experience motor fluctuations not adequately controlled by oral medications.
- Patient experience: Patients or caregivers can manage the pump and change the injection site every few days. Clinical trials showed an average of 2.7 more hours of 'on' time per day compared to oral medication.
Onapgo (apomorphine hydrochloride)
Approved by the FDA in February 2025, Onapgo is a continuous subcutaneous infusion for motor fluctuations in progressing PD. Unlike Vyalev, it delivers apomorphine, a dopamine agonist that mimics the effects of dopamine in the brain.
- How it works: The continuous infusion bypasses the gastrointestinal tract, ensuring more reliable and consistent absorption compared to oral medications.
- Who it's for: People experiencing motor fluctuations and significant 'off' time that aren't managed with existing oral medications.
- Patient experience: Delivered via a wearable pump, Onapgo can provide more predictable symptom control. Availability is expected in the second quarter of 2025.
Crexont (carbidopa and levodopa extended-release)
This oral capsule formulation was approved by the FDA in August 2024 for the treatment of PD. Formerly known as IPX203, Crexont combines immediate-release granules and extended-release pellets to provide a longer duration of effect.
- How it works: This innovative design provides a more sustained therapeutic effect, extending 'on' time with less frequent dosing compared to immediate-release oral formulations.
- Who it's for: PD patients experiencing motor fluctuations who are looking for better symptom control with fewer daily doses.
- Patient experience: In clinical trials, patients on Crexont experienced extended 'on' time and less frequent motor fluctuations. It offers a less invasive option compared to infusion pumps.
Comparison of New Parkinson's Medications
| Feature | Vyalev (foscarbidopa/foslevodopa) | Onapgo (apomorphine hydrochloride) | Crexont (carbidopa/levodopa) |
|---|---|---|---|
| Delivery Method | Continuous 24-hour subcutaneous infusion via a pump | Continuous subcutaneous infusion via a wearable pump | Oral extended-release capsules |
| Drug Type | Levodopa/Carbidopa Prodrugs | Dopamine Agonist (apomorphine) | Levodopa/Carbidopa Extended-Release |
| Target Population | Adults with advanced PD experiencing motor fluctuations | Patients with progressing PD experiencing motor fluctuations and significant 'off' time | PD patients with motor fluctuations looking for fewer daily doses |
| Key Benefit | 24-hour continuous symptom control and increased 'on' time | Consistent delivery bypassing GI tract issues, providing more predictable control | Longer duration of 'on' time with less frequent dosing compared to immediate-release versions |
| Side Effects | Injection site reactions, dyskinesia, hallucinations | Injection site reactions, nausea, sleepiness, headaches | Nausea, anxiety, dizziness |
Promising Treatments in the Pipeline
Beyond approved drugs, significant research is underway for therapies that could potentially modify the disease's progression rather than just manage symptoms.
Tavapadon
This is an investigational, selective dopamine receptor agonist that has completed Phase 3 trials and is expected to be submitted to the FDA. Unlike earlier, less selective dopamine agonists, Tavapadon aims to provide good symptomatic control with potentially fewer side effects, including visual hallucinations and compulsive behaviors. It is being studied both as a monotherapy and as an adjunct to levodopa.
Bemdaneprocel (BRT-DA01)
This is a cell-based therapy that aims to replace the dopamine-producing neurons lost in PD. Developed by BlueRock Therapeutics, it involves surgically transplanting dopaminergic neuron precursor cells into the brain. Based on positive Phase 1 data, it was granted a regenerative medicine advanced therapy designation by the FDA and is set to enter Phase 3 trials in 2025.
Disease-Modifying Therapies
Researchers are also exploring therapies that target the underlying pathology of PD. These include treatments aiming to: target abnormal alpha-synuclein aggregation, increase the activity of certain enzymes, decrease inflammation, and enhance nerve survival through neurotrophic growth factors. These therapies are still in earlier stages of development but hold promise for fundamentally altering the course of the disease.
Considerations for Patients
The choice of medication depends on several factors, including the stage of the disease, specific symptoms, and individual patient needs. For early-stage patients, standard oral medication might suffice. As the disease progresses and motor fluctuations become a problem, advanced therapies like continuous infusions or extended-release capsules may be considered. These treatments offer more consistent symptom control but may come with different side effects or lifestyle considerations.
It is crucial for patients to have an open and detailed discussion with their neurologist, preferably a movement disorder specialist, to evaluate the best treatment strategy. They can weigh the benefits of each new therapy against potential side effects and logistical considerations, ensuring the chosen approach aligns with the patient's lifestyle and goals.
Conclusion
While there is no cure for Parkinson's disease, recent advancements in medications and delivery methods have significantly improved treatment options. The introduction of continuous infusion systems like Vyalev and Onapgo, along with extended-release oral options like Crexont, mark a major step forward in managing advanced PD and alleviating motor fluctuations. Looking to the future, promising pipeline candidates like Tavapadon and cell-based therapies like bemdaneprocel offer hope for even more targeted, effective, and potentially disease-modifying treatments. These innovations empower patients and clinicians with more personalized and consistent strategies to maintain a higher quality of life.
