Knight Therapeutics Inc. has announced that Health Canada has accepted its New Drug Submission (NDS) for CREXONT, a novel oral formulation of carbidopa/levodopa extended-release capsules designed to treat Parkinson's disease. The submission represents a significant milestone for the Montreal-based specialty pharmaceutical company as it expands its central nervous system portfolio.
Novel Formulation Technology
CREXONT features an innovative dual-release design that combines immediate-release granules with extended-release beads. The immediate-release granules contain carbidopa and levodopa with a disintegrant polymer for rapid dissolution, while the extended-release beads are coated with a sustained release polymer and a mucoadhesive polymer designed to prolong adhesion at the absorption site. An enteric coating prevents premature disintegration in the stomach.
This unique formulation allows for rapid onset while leveraging the mucoadhesive polymer for slow levodopa release, potentially enabling longer levodopa absorption in the gut compared to conventional immediate-release formulations.
Phase 3 Trial Results
CREXONT was evaluated in the RISE-PD clinical study, a 20-week, randomized, double-blind, double-dummy, active-controlled phase 3 clinical trial involving 630 patients. The study successfully met both its primary and secondary endpoints.
Treatment with CREXONT significantly improved daily "Good On" time compared to immediate-release carbidopa/levodopa, showing an improvement of 0.53 hours (least squares mean, 95% CI, 0.09-0.97). Notably, patients achieved this improvement with reduced dosing frequency, averaging three times per day versus five times per day for immediate-release formulations.
A post-hoc analysis of the primary endpoint demonstrated 1.55 more hours of "Good On" time per dose of CREXONT compared to immediate-release carbidopa/levodopa.
Safety Profile
The most common adverse reactions with CREXONT, occurring at an incidence of ≥3% and greater than immediate-release carbidopa/levodopa, were nausea and anxiety. Healthcare providers are advised to avoid sudden discontinuation or rapid dose reduction with CREXONT and should work with patients to taper the dose over time if discontinuing to reduce the risk of fever or confusion.
Market Opportunity and Commercial Strategy
CREXONT is expected to compete in substantial markets, with over $50 million in Canada and over $120 million in Brazil. The controlled release portion of these markets was valued at $15 million each during the twelve-month period ended September 2024, according to IQVIA data.
In January 2024, Knight entered into an agreement with Amneal Pharmaceuticals Inc. for exclusive rights to seek regulatory approval and commercialize CREXONT in Canada and Latin America. The company is also working to submit marketing authorization applications in Mexico and Brazil during 2025.
"The submission of CREXONT in Canada highlights Knight's ongoing commitment to enhancing our central nervous system (CNS) portfolio," said Samira Sakhia, President and CEO of Knight. "With a significant unmet medical need in Parkinson's disease treatment, CREXONT will offer a valuable new therapeutic option for the patients."
Addressing Growing Disease Burden
Parkinson's disease has become the fastest growing neurological disorder worldwide, with approximately 1 million patients diagnosed in the United States. In Canada, over 100,000 people live with Parkinson's disease as of 2021, with an estimated 6,600 new diagnoses occurring annually based on an annual incidence rate of 20 new cases per 100,000 people.
The progressive disorder affects dopamine-producing neurons in the brain and is characterized by slowness of movement, stiffness, resting tremor, and impaired balance. While not considered fatal, Parkinson's disease is associated with significant morbidity and disability. With an average age at diagnosis of 60 and increasing longevity, the number of patients living with Parkinson's disease is predicted to grow significantly over the coming decades.
