Med Check: Vyalev for Advanced Parkinson’s, Lumryz for Children with Narcolepsy, Synthetic Cannabis for Agitation in Alzheimer’s, and More

In October, the Food and Drug Administration (FDA) approved Vyalev (foscarbidopa/foslevodopa) for the treatment of motor fluctuations in adults with advanced Parkinson’s disease, Abbvie announced. Vyalev is a subcutaneous 24-hour infusion of foscarbidopa, a prodrug of carbidopa, and foslevodopa, a prodrug of levodopa.

The approval was based on the Phase 3 M15-736 trial of 141 adults with advanced Parkinson’s. Patients were randomized to receive either a continuous subcutaneous infusion of Vyalev and oral placebo capsules (the treatment group) or a subcutaneous infusion of placebo solution plus oral capsules containing carbidopa and levodopa (the control group) for 12 weeks. The primary endpoint was the change from baseline to week 12 in good “on” time, defined as “on” time without troublesome dyskinesia plus “on” time with non-troublesome dyskinesia, as recorded in patient diaries. Data for the primary endpoint was collected and averaged over three consecutive days and normalized to a typical 16-hour waking period.

At week 12, “on” time without troublesome dyskinesia increased 2.72 hours for patients in the treatment group, compared with .97 hours for the control group. In addition, the amount of “off” time, defined as periods in which troublesome symptoms returned, decreased 2.75 hours for the treatment group compared with .96 hours for the control group.

The FDA approved Avadel Pharmaceuticals’ supplemental new drug application for Lumryz (sodium oxybate) extended-release oral suspension for the treatment of cataplexy or excessive daytime sleepiness in patients age 7 years or older, the company announced in October. Lumryz is taken once a day at bedtime.

The expanded approval was supported by data from a Phase 3 trial of Jazz Pharmaceuticals’ immediate-release formulation of sodium oxybate, Xyrem, which included 106 patients ages 7 to 17 years with narcolepsy and a baseline history of at least 14 cataplexy attacks in a typical two-week period. Following an open-label titration period to reach a tolerable and effective dose, 63 of the patients were randomized to continue receiving Xyrem or to receive placebo for two more weeks. (The remaining patients continued receiving open-label Xyrem.)

Patients in the placebo group experienced a median increase of 12.7 cataplexy attacks compared with a median increase of .3 cataplexy attacks in the continued treatment group. Scores on the Epworth Sleepiness Scale increased a median of three points for patients in the placebo group, compared with no increase in the continued treatment group.

Lumryz has a boxed warning as a central nervous system depressant and for its potential for abuse and misuse. It is available only through a restricted program under a Risk Evaluation and Mitigation Strategy called the Lumryz REMS.

In October, Denovo Biopharma announced that the FDA granted Fast Track designation to its investigational serotonin, norepinephrine, and dopamine reuptake inhibitor DB104 (liafensine) for treatment-resistant depression. The FDA Fast Track is a process designed to expedite the development and review of drugs that treat serious conditions and fill an unmet medical need.

The FDA’s Fast Track designation is supported by data from the Phase 2b ENLIGHTEN trial, which enrolled 197 adults with treatment-resistant depression. According to Denovo, its artificial intelligence and whole genome sequencing–based biomarker platform led to the discovery of a novel genetic biomarker named DGM4. To be eligible for the ENLIGHTEN trial, patients had to have DGM4 genotype results obtained from a designated CLIA lab.

Patients were randomized to receive 1 mg or 2 mg of liafensine or placebo for six weeks. Although both DGM4-positive and DGM4-negative patients were included in the trial, only DGM4-positive patients who received liafensine had a significant improvement in depression symptoms at six weeks as measured by the Montgomery-Åsberg Depression Rating Scale. There were no reports of side effects common for drugs approved for treatment-resistant depression, such as dissociation, respiratory depression, movement disorders, and metabolic dysfunction with morbid weight gain.

Indivior announced in October that the FDA had granted priority review for the company’s Prior Approval Supplement (PAS) for Sublocade (buprenorphine extended-release) injection.

The PAS seeks two proposed updates to the Sublocade label. The first update would expand injection sites from the current subcutaneous abdominal injection site to include the thigh, buttock, and back of the upper arm for induction and maintenance. The second update would include a rapid induction protocol that reduces treatment induction time from the current seven-day minimum of transmucosal buprenorphine to a single dose of transmucosal buprenorphine with a one-hour observation period to confirm tolerability. This protocol would also allow for the second 300 mg dose to be administered as early as one week after the initial 300 mg injection, based on what the patient needs.

The deadline for an FDA decision is February 7, 2025.

A pill form of the drug dronabinol, an FDA-approved synthetic version of tetrahydrocannabinol (THC) approved for treating nausea and vomiting caused by chemotherapy, may reduce agitation in patients with Alzheimer’s disease by an average of 30%, according to a study by researchers at the Johns Hopkins University and Tufts Medical Center. The findings were presented at an International Psychogeriatric Association conference in Buenos Aires in September.

In the study, 75 patients with severe Alzheimer’s agitation as measured by the Pittsburgh Agitation Scale (PAS) and the Neuropsychiatric Inventory Agitation/Aggression subscale (NPI-C) were randomized to receive either 5 mg of oral dronabinol or placebo pill twice daily for three weeks. The PAS scores in the dronabinol group dropped from an average of 9.68 to an average of 7.26 after three weeks, compared with no change in the placebo group. Average scores on the NPI-C also improved in the dronabinol group compared with the placebo group. Dronabinol was well-tolerated by patients compared with current treatments for agitation. ■