FDA approves extended-release levodopa/carbidopa, now Crexont
Treatment led to improvement in good on time in Phase 3 trial
Note: This article was updated Aug. 9, 2024, to correct that the improvement seen in good on time in additional analyses was 1.5 hours per dose.
The U.S. Food and Drug Administration (FDA) has approved IPX203, a novel extended-release formulation of levodopa and carbidopa, for Parkinson’s disease.
Amneal Pharmaceuticals will be marketing the newly approved therapy under the brand name Crexont, which is expected to be available to patients in the U.S. in September.
“The approval of Crexont is a seminal moment in the treatment paradigm for Parkinson’s disease,” Chirag and Chintu Patel, co-CEOs of Amneal, said in a company press release.
Parkinson’s is caused by the progressive dysfunction and death of brain cells that are responsible for making dopamine, a crucial neurotransmitter (brain signaling molecule). The lack of dopamine signaling ultimately drives most disease symptoms.
Levodopa is a mainstay Parkinson’s treatment that basically works by giving brain cells more raw materials with which to manufacture dopamine. It is commonly given alongside carbidopa, which allows more levodopa to reach the brain.
Side effects with long-term frequent dosing of levodopa/carbidopa
Although levodopa/carbidopa can be effective for managing Parkinson’s symptoms, patients taking the therapy long term will usually start to experience off episodes where symptoms aren’t well controlled between scheduled doses. Long-term use of the therapy can also cause dyskinesia (uncontrolled movements) as a side effect.
Off time and side effects like dyskinesia cause “a notable decrease in quality of life over time” for people living with Parkinson’s, said Andrea Merriam, CEO of the Parkinson & Movement Disorder Alliance.
Crexont is a novel formulation of levodopa/carbidopa that combines immediate-release granules alongside extended-release pellets. This formulation is designed to deliver a steady amount of the therapy into the body, maintaining therapeutic levels while requiring less frequent dosing to maximize good on time where symptoms are well controlled without troublesome dyskinesia.
“Some [Parkinson’s] patients on [immediate release levodopa/carbidopa] take up to 10 daily doses and still experience motor fluctuations,” the Patels said. “Crexont’s innovative formulation provides a longer duration of ‘Good On’ time with less frequent dosing compared to [immediate release levodopa/carbidopa].”
Amneal originally asked the FDA to approve Crexont in 2022, but the agency requested more safety data before it could decide on whether to approve the application. Amneal resubmitted its application earlier this year.
The application is based mainly on data from a Phase 3 trial called RISE-PD (NCT03670953), which tested Crexont against an immediate-release formulation of levodopa/carbidopa in more than 500 people with Parkinson’s.
Patients on Crexont had significantly more good on time each day
Results showed patients given Crexont had significantly more good on time each day, by about half an hour per day. Additional analyses accounting for other factors suggested the increase in good on time was even more dramatic, at more than 1.5 hours per dose.
The improvement in good on time “represents a substantial advancement in managing motor symptoms and maintaining more consistent therapeutic effects, which is very encouraging for both patients and the Parkinson’s community,” said Robert A. Hauser, MD, a professor at the University of South Florida and director of the Parkinson’s Disease & Movement Disorders Center.
Long-term data showed Crexont’s effect was consistent over months of treatment, with most side effects being mild or moderate and happening within the first three months of treatment. The most common side effects of Crexont are nausea and anxiety, according to the therapy’s prescribing information.
“As the [Parkinson’s] community explores treatment options that address the challenges faced by people with Parkinson’s disease and their families, we champion advances like Crexont that improve ‘Good On’ time, allowing people more time to do the things they love with the people they love,” Merriam said.
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