22 Jun Parkinson’s Disease: FDA Approves Sublingual KYNMOBI™ For Faster Treatment of OFF Episodes
MedicalResearch.com Interview with:
Stewart A. Factor, D.O.
Professor of Neurology
Director of the Movement Disorders Program
Vance Lanier Chair of Neurology
Emory University School of Medicine
MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by OFF episodes.
Response: Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disease characterized by motor symptoms, including tremor at rest, rigidity and impaired movement, as well as significant non-motor symptoms, such as cognitive impairment, psychiatric symptoms and autonomic symptoms (i.e. urinary issues, constipation, low blood pressure). It is the second-most common neurodegenerative disease after Alzheimer’s disease and it is predicted that the prevalence of Parkinson’s disease will double by the year 2040. The symptoms of PD are in substantial part, due to loss of dopamine nerve cells in the brain. The current standard of care for PD includes replacing the dopamine loss by the use of oral carbidopa/levodopa. Levodopa is a precursor of dopamine, converted in the brain.
OFF episodes have been a significant unmet need in Parkinson’s disease since the emergence of levodopa. Initially, levodopa controls PD symptoms in a continuous fashion throughout the day. With time the response becomes less predictable and patients experience a re-emergence or worsening of PD symptoms. These episodes are what we mean by OFF episodes. OFF episodes can be characterized, in part, by re-emergence of motor symptoms including tremor, stiffness or slowed movement that can happen at any point during the day. OFF episodes typically begin within the first five years of treatment and occur at the end of a dose. This is referred to as end of dose failure or wearing off. Within the first four to six years after diagnosis, regardless of disease severity, up to 60 percent of people with PD experience OFF episodes. With time these episodes become longer, more severe and disabling, more frequent and less predictable as PD progresses. They can take up more than half the day
OFF episodes may alter a persons’ ability to perform everyday activities by slowing or even precluding their completion. The result is significant burden and distress for people living with Parkinson’s disease (PD) and their care partners.
CTH-300 was a Phase 3, 12-week, randomized, double-blind, placebo-controlled, parallel group, study examining the efficacy, safety and tolerability of apomorphine hydrochloride sublingual film (KYNMOBI) in people with levodopa-responsive PD complicated by OFF episodes. The primary endpoint was a mean change in the score from pre-dose in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III Motor Examination at 30 minutes after dosing at the 12-week visit of the maintenance treatment phase. The key secondary endpoint was the percentage of people with PD with a patient-rated full ON (or best) response within 30 minutes at the 12-week visit of the maintenance treatment phase.
How does KYNMOBI™ differ from other medications for PD?
KYNMOBI is the first and only FDA-approved medicine for the acute, intermittent treatment of OFF episodes in patients with PD that is administered sublingually. KYNMOBI dissolves under the tongue to help people with PD to improve their OFF symptoms as needed.
The novel sublingual formulation allows for the delivery of apomorphine, a non-ergot dopamine agonist, through the oral mucosa, bypassing the GI tract and avoiding levodopa absorption issues common in PD patients.
MedicalResearch.com: What are the main findings of the underlying studies?
Response: Phase 3 clinical trial results, published in Lancet Neurology, found that patients who received KYNMOBI experienced statistically significantly greater improvement in motor control (e.g., improved ability to rise from a chair) at 30 minutes after dosing at week 12, compared to placebo, with clinical improvements seen at 15 minutes post-administration and lasting at least 90 minutes. Further highlights include:
- Patients with PD who received KYNMOBI had a statistically significant LS mean reduction (7.6 points) in the MDS-UPDRS Part III score from pre-dose to 30 minutes after dosing, compared to placebo — meaning observable improvements in tested motor characteristics of OFF episodes, including improved ability to walk, as well as other hand and foot movements.
- Additionally, a significantly higher percentage of patients with PD treated with KYNMOBI had a patient-rated full ON response within 30 minutes at week 12, compared with patients with PD receiving placebo.
- In an analysis evaluating a secondary endpoint of efficacy of self-administered dosing of KYNMOBI at home compared with placebo for the treatment of PD OFF episodes, 79% of instances self-reported a full ON response at 30 minutes post-dose with KYNMOBI compared to 31% with placebo.
MedicalResearch.com: What should readers take away from your report?
Response: Approximately 350,000 people in the U.S. with PD experience OFF episodes, which can be highly disruptive. Within the first four to six years after diagnosis, approximately 40-60% of people with PD experience OFF episodes. By 10 years, nearly every person with PD has experienced an OFF.
Despite the prevalence and daily impact, most treatments for OFF episodes have focused on keeping patients ON versus treating episodes as they occur.
With KYNMOBI, people with PD will now have a new treatment option that dissolves under the tongue, to help improve their OFF symptoms where and when they occur.
Dr. Factor has the following disclosures:
Honoraria: Lundbeck, Sunovion, Biogen, Acadia, Impel, Acorda, CereSpir.
Grants: Medtronics, Boston Scientific, Biohaven, Impax, Lilly, US World Meds, Sunovion, Vaccinex, Voyager, Jazz Pharmaceuticals, CHDI Foundation, Michael J. Fox Foundation, NIH(U10 NS077366), Parkinson Foundation
Royalties: Demos, Blackwell Futura, Springer for textbooks, Uptodate
Other Bracket Global LLC, CNS Ratings LLC
FDA approval of KYNMOBI™ (apomorphine hydrochloride) sublingual film for the acute, intermittent treatment of OFF episodes in patients with Parkinson’s disease.
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