Med Check: Alzheimer’s Agitation, Idiopathic Hypersomnia, Depression, and More

Axsome Therapeutics’ investigational combination drug AXS-05 (45 mg dextromethorphan/105 mg bupropion) may delay relapse of agitation associated with Alzheimer’s disease, the company announced in November.

In the phase 3 ACCORD trial, 108 patients with Alzheimer’s disease agitation who had already responded to AXS-05 in a previous, open-label trial either continued treatment with the drug or were switched to placebo for up to 26 weeks. Relapse was defined as a worsening of 10 points or more on the Cohen-Mansfield Agitation Inventory (CMAI) from the time the patients were randomized to either continued treatment or to placebo, a CMAI total score greater than when they entered the study, or hospitalization or other institutionalization because of agitation associated with Alzheimer’s disease.

Patients who took AXS-05 had a 3.6-fold lower risk of relapse compared with those who took placebo. During the trial, 7.5% of patients who took the drug experienced a relapse of Alzheimer’s disease agitation, compared with 25.9% of those who took placebo.

 

The Food and Drug Administration (FDA) has granted orphan drug status to serdexmethylphenidate for the treatment of idiopathic hypersomnia, KemPharm Inc. announced in November. Serdexmethylphenidate is KemPharm’s prodrug of d-methylphenidate.

The FDA may grant orphan drug status to investigational therapies that address rare medical diseases or conditions. If the drug later receives FDA approval for treating the disease or condition, the FDA may not approve any other applications to market the same drug for the same indication for seven years, except in limited circumstances.

KemPharm will soon begin a phase 2 trial of serdexmethylphenidate in patients with idiopathic hypersomnia and a second trial in patients with narcolepsy.

Serdexmethylphenidate is also an active ingredient in Corium’s Azstarys (serdexmethylphenidate and dexmethylphenidate), which the FDA approved in March of 2021 for treating symptoms of attention-deficit/hyperactivity disorder in patients aged 6 years and older.

 

An open-label phase 3b trial suggests that Spravato (esketamine nasal spray) may have greater efficacy than quetiapine extended release (XR) for treating symptoms of treatment-resistant depression (TRD) in adults, Janssen Pharmaceutical Companies announced in November. Janssen is the manufacturer of Spravato.

In the ESCAPE-TRD trial, 676 patients with TRD were randomized to receive either Spravato or quetiapine XR, both in combination with a continuing selective serotonin reuptake inhibitor or serotonin and norepinephrine reuptake inhibitor, for 32 weeks. At the eighth week, 21.7% of the patients who received Spravato experienced remission of their symptoms, compared with 14.1% of those who took quetiapine. At study’s end, symptoms abated in 55% of patients who took Spravato, compared with 37% of those who took quetiapine

 

In November, Amneal Pharmaceuticals Inc. announced that the FDA has accepted for review the company’s New Drug Application for IPX203 (carbidopa/levodopa extended release) for the treatment of Parkinson’s disease.

In the phase 3 RISE-PD trial, 506 patients who were at least 40 years old when they were diagnosed with Parkinson’s disease were randomized to receive either IPX203 or immediate-release carbidopa/levodopa. All patients had motor fluctuations.

The primary endpoint was change from baseline in the daily amount of “Good On” time, defined as the sum of “On” time without dyskinesia and “On” time with non-troublesome dyskinesia. At the twentieth week, those who took IPX203 had an average of roughly half an hour more of “Good On” time compared with those who took immediate-release carbidopa/levodopa.

In addition, a study published in the May 2022 Neurology found that 29.7% of patients who took IPX203 were “much improved” or “very much improved,” as evidenced in their scores on the Patient Global Impression of Change, compared with 18.8% of those who took immediate-release carbidopa/levodopa. ■