Introducing Crexont: The New Oral Carbidopa-Levodopa
For decades, carbidopa-levodopa has been the gold-standard treatment for managing the motor symptoms of Parkinson's disease (PD). However, the short half-life of immediate-release formulations often leads to motor fluctuations, where patients experience periods of good symptom control ('ON-time') followed by periods of worsening symptoms ('OFF-time'). Addressing this challenge, the U.S. Food and Drug Administration (FDA) approved Crexont® (carbidopa and levodopa) extended-release capsules in August 2024. Developed by Amneal Pharmaceuticals, Crexont represents a next-generation oral formulation designed to provide a more consistent and prolonged therapeutic effect.
How Crexont's Technology Works
Crexont utilizes a novel drug delivery system. The capsule contains immediate-release granules for a quick onset and extended-release pellets with a mucoadhesive polymer. This mucoadhesive coating helps the pellets adhere to the upper small intestine, where levodopa is best absorbed, ensuring a slower, more gradual release. An enteric coating further protects the pellets until they reach the small intestine. This multi-layered approach allows for a stable and continuous level of medication over a longer period, reducing the need for frequent dosing and smoothing out motor fluctuations.
Clinical Trial Results: The Promise of Crexont
Crexont's approval was based on data from the pivotal Phase 3 RISE-PD clinical trial comparing it to immediate-release carbidopa-levodopa in patients with motor fluctuations. The study showed that patients on Crexont had an average increase of 0.53 hours of 'Good ON-time' per day, despite being dosed less often (an average of three times daily versus five times daily). Per dose, Crexont provided approximately 1.55 hours more 'Good ON-time' than the immediate-release formulation. Common side effects in the trial included nausea and anxiety.
Comparison of Carbidopa-Levodopa Formulations
To understand Crexont's place in treatment, it's helpful to compare it with other available formulations.
| Feature | Immediate-Release (IR) Carbidopa-Levodopa | Rytary® (Extended-Release) | Crexont® (Extended-Release) |
|---|---|---|---|
| Mechanism | Simple tablet formulation; rapid onset, short duration. | Complex capsule with different types of beads for varied release rates. | Complex capsule with immediate-release granules, and extended-release pellets with a mucoadhesive polymer. |
| Dosing Frequency | High, often 4-5 times or more per day as PD progresses. | Lower, typically 3-4 times per day. | Lower, typically 2-4 times per day (study averaged 3 times). |
| ON-time | Short duration per dose, leading to motor fluctuations. | Prolonged ON-time compared to IR, helps smooth fluctuations. | Significantly prolonged ON-time per dose due to mucoadhesive technology. |
| Absorption | Primarily dependent on gastric emptying, leading to variability. | Improved absorption profile, less sensitive to food intake than IR. | Optimized absorption due to mucoadhesive layer keeping pellets at optimal absorption site longer. |
Considering Other Recent Advancements
Beyond oral medications, other device-aided therapies are changing the landscape for advanced Parkinson's disease patients. For instance, Vyalev™, a 24-hour continuous subcutaneous infusion of foslevodopa/foscarbidopa, was also approved in 2024. Vyalev provides steady, around-the-clock symptom control, which can be a valuable option for those who do not respond well to oral therapies alone.
Conclusion
While levodopa has been a foundational therapy for Parkinson's disease for decades, innovations like Crexont demonstrate that the field is far from stagnant. Crexont's unique delivery mechanism provides a more consistent and sustained release of medication, directly addressing the motor fluctuations that significantly impact a patient's quality of life. This new drug for carbidopa-levodopa is a welcome addition to the growing arsenal of treatments, offering clinicians and patients another valuable tool for personalized care. For those considering new options, a conversation with a healthcare provider is the best next step to determine if Crexont or another recent advancement is the right fit. For more information, you can visit resources like {Link: The Michael J. Fox Foundation for Parkinson's Research https://www.michaeljfox.org/news/fda-approves-new-levodopacarbidopa-formulation-use-parkinsons}.
