A New Extended-Release Levodopa Formulation

In August 2024, the FDA approved a new Parkinson’s medication, CREXONT®.  

CREXONT, which was developed by Amneal, is a novel oral formulation of carbidopa/levodopa. This new formulation combines extended-release pellets and immediate-release granules of carbidopa/levodopa. CREXONT can provide people with Parkinson’s more ON-time each day, with fewer daily doses and less troublesome dyskinesia. 

The new treatment will be available in the United States on September 23, 2024. 

ABOUT CREXONT 

CREXONT is an innovative formulation of carbidopa/levodopa that consists of immediate-release granules with carbidopa and levodopa for “rapid onset of action” and extended-release pellets with levodopa for longer-lasting efficacy.  

CREXONT is the longest-lasting formulation of oral carbidopa/levodopa because of its novel technology. The extended-release pellets in CREXONT are coated in a “mucoadhesive polymer,” which helps the medication stick to parts of the digestive system where the medication will absorb more effectively and deliver a steady amount of carbidopa/levodopa for a longer period. This provides extended stretches of symptom relief and allows for less-frequent dosing.  

ABOUT CARBIDOPA/LEVODOPA 

To understand how CREXONT works, it may help to review the basics of carbidopa/levodopa. 

Many Parkinson’s symptoms are caused by having low levels of dopamine in the brain. Levodopa has been the gold-standard Parkinson’s medication for almost 50 years, and many different formulations of the drug exist. Levodopa helps with Parkinson’s symptoms because it is converted into dopamine in the body. More dopamine means less significant Parkinson’s symptoms. Carbidopa is taken with levodopa to reduce nausea associated with taking levodopa in isolation. 

Unfortunately, each dose of oral immediate-release carbidopa/levodopa medications is effective for a relatively short period of time. This short effective window and the fact that Parkinson’s progresses mean that, over time, more and more levodopa is needed. Some people with Parkinson’s eventually require levodopa or related drugs many times each day to manage their symptoms. It is not uncommon for us to talk with people who take Parkinson’s medication 10 or more times each day.

The need to take 10 daily doses of any medication is impactful enough on a person’s life, but a particularly troublesome complication sometimes results from long-term use of high doses of levodopa: dyskinesia.

Levodopa-induced dyskinesia can be described as uncontrolled jerking, dance-like or wriggling movements. Dyskinesia can be anything from minor tics to full-body movements. It can be a stand-alone condition; however, in people with Parkinson’s, it is most often associated with long-term use of carbidopa/levodopa. The reason for this association is that higher, more frequent doses of levodopa can lead to fluctuations of the level of levodopa in a person’s body. These fluctuations lead to irregular, uncontrolled movements.

CREXONT is designed to address both the need for more frequent dosing as Parkinson’s progresses and the goal of limiting dyskinesia. The RISE-PD study, one of the trials that provided evidence the FDA considered when approving CREXONT, showed that CREXONT impacted both of these aspects of living with Parkinson’s. 

More About Crexont

RISE-PD was a phase three trial that tested CREXONT against immediate-release formulation of carbidopa/levodopa in more than 500 people with Parkinson’s.

Results from the RISE-PD trial showed that participants who received CREXONT had significantly more ON-time without troublesome dyskinesia each day, by about 30 minutes per day, even when dosed less frequently than those receiving immediate-release carbidopa/levodopa.

Additional analyses accounting for other factors suggested the increase in good ON-time was even more significant than the data initially showed. These analyses showed that when compared dose-by-dose to immediate-release carbidopa/levodopa, CREXONT delivered 1.5 hours more good ON-time per dose than immediate-release carbidopa-levodopa.  

The results of the RISE-PD trial showed that therapeutic benefits of CREXONT include:

• More good ON-time with less frequent dosing 

• Significant improvement of 0.5 hours of additional good ON-time per day compared to immediate-release carbidopa/levodopa 

• A post-hoc analysis of the primary study endpoint on a per-dose basis showed 1.6 hours additional good ON-time per dose of CREXONT compared to immediate-release carbidopa/levodopa 

• An average of three-times daily dosing with CREXONT compared to five-times daily dosing with immediate-release carbidopa/levodopa 

• Safety profile consistent with immediate-release carbidopa/levodopa 

SAFETY AND SIDE EFFECTS 

CREXONT’s safety and tolerability profile is detailed in an open-label extension study. This nine-month extension study enrolled participants who completed the RISE-PD trial. The extension study was held at 94 sites in the United States, Italy, Spain, France, United Kingdom, Czech Republic, Poland, and Germany. Results showed that improvements in efficacy were maintained and dosing frequency and total daily dose remained stable through the trial.  

A total of 52.7% of participants experienced one or more treatment-emergent “adverse events,” which were mostly mild or moderate and occurred within the first 90 days of treatment. The most common adverse side effects were nausea and anxiety.   

Overall, in the Phase 3 open-label extension, CREXONT exhibited a favorable safety and tolerability profile. 

WHAT’S NEXT 

Amneal plans to make CREXONT available in the United States beginning on September 23, 2024. If you think CREXONT might be helpful to you, talk with your care team.

As with any treatment, consult with your insurance provider to confirm your costs, but Amneal will also offer support solutions to help with medication access and affordability, with services from Cover My Meds and Amneal’s Patient Support Program. 

Note, too, that Amneal plans to continue to produce RYTARY®, an earlier generation of extended-release carbidopa/levodopa, and ONGENTYS®, an add-on therapy used in conjunction with other Parkinson’s medications.  

ADDITIONAL RESOURCES 

View the FDA’s Full Prescribing Information guide for CREXONT, RYTARY, and ONGENTYS. 

Explore our Parkinson’s Medications database, where you can learn about the different types of Parkinson’s medications, the names of common Parkinson’s medications, and the symptoms that can be managed by using these medications. There are many different classes of medications that offer options for people with mild to advanced Parkinson’s symptoms. Treatment discoveries are also progressing at a rapid pace, and new medications are continually added to the growing list. Remember, it’s essential that you talk to your physician if your medications aren’t working or you’re interested in trying something new. 

This post was written by the Davis Phinney Foundation.  

This post is sponsored by Amneal.