Med Check: NDA for MDMA-Assisted Therapy and More

In December the Multidisciplinary Association for Psychedelic Studies submitted a New Drug Application (NDA) to the Food and Drug Administration (FDA) for 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder (PTSD), the organization announced.

In a phase 3 randomized, double-blind, placebo-controlled study of MDMA-assisted therapy, participants with severe PTSD were assigned to receive either manualized therapy with MDMA (n=46) or with placebo (n=44) at one of 15 study sites across the United States, Canada, and Israel. Participants underwent three eight-hour experimental sessions spaced four weeks apart with a single divided dose of 80 to 180 mg MDMA or placebo, in addition to three preparatory and nine integrative therapy sessions. In the first experimental session, participants received an initial dose of 80 mg followed by a supplemental half-dose of 40 mg, 1.5 to 2.5 hours later. In the second and third experimental sessions, participants received an initial dose of 120 mg followed by a supplemental half-dose of 60 mg. Each experimental session was followed by three 90-minute integrative therapy sessions spaced one week apart to allow participants to incorporate their experiences.

At 18 weeks, participants in the MDMA group showed a significant reduction in PTSD symptoms, as assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Total scores dropped by a mean of 24.4 points for those who took MDMA compared with 13.9 points in those in the placebo group. In addition, at 18 weeks, 67% of participants in the MDMA group no longer met diagnostic criteria for PTSD, compared with 32% of participants in the placebo group.

In December Karuna Therapeutics published the results of its phase 3 EMERGENT-2 trial of KarXT (xanomeline-trospium) in adults with schizophrenia in The Lancet.

The phase 3 EMERGENT-2 trial was a double-blind, placebo-controlled, five-week inpatient trial that enrolled 252 adults with schizophrenia in the United States. Participants took either a twice-daily, flexible dose of KarXT or placebo. Schizophrenia symptoms were measured by the Positive and Negative Syndrome Scale (PANSS). At week 5, total PANSS scores were an average of 9.6 points lower in patients who took KarXT compared with those who took placebo.

Results published in The Lancet also include data for all the pre-specified secondary outcome measures: change in PANSS positive subscale, PANSS negative subscale, PANSS Marder negative factor, Clinical Global Impression-Severity score, and percentage of participants achieving a ≥30% reduction from baseline to week 5 in PANSS total score.

The most common adverse events with KarXT versus placebo were constipation (21% versus 10%), dyspepsia (19% versus 8%), nausea (19% versus 6%), and vomiting (14% versus 1%).

In December Teva Pharmaceuticals announced that Ajovy (fremanezumab injection) reduced migraine attacks in patients with migraine and comorbid obesity in two clinical trials.

A post hoc analysis of the HALO-LTS and FOCUS phase 3 studies examined the safety and efficacy of fremanezumab migraine preventive treatment in people with a history of migraines who had a body mass index (BMI) of at least 30 kg/m2 (the cutoff for obesity) compared with those of lower BMI over a six-month period. There were 578 people in the BMI-high group and 1,859 in the BMI-normal group.

The analysis showed that the efficacy of fremanezumab was the same in migraine patients with BMI-high compared with BMI-normal patients. At baseline, there were 13.7 and 13.6 monthly migraine days in BMI-high and BMI-normal patients, respectively. After six months of treatment with fremanezumab, there were 6.8 monthly migraine days in BMI-high patients compared with 7.2 in BMI-normal patients. Adverse events were similar in both groups.

The FDA has accepted for review an NDA for ALPHA-1062, a prodrug of the acetylcholinesterase inhibitor galantamine, Alpha Cognition announced in December.

The NDA submission includes data from studies that demonstrated bioequivalence for ALPHA-1062 to galantamine and galantamine extended-release (ER). A bioequivalence study, designed to compare ALPHA-1062 to galantamine hydrobromide (a standard treatment for patients with mild to moderate Alzheimer’s disease), showed ALPHA-1062 achieved amounts of medication in the body similar to the immediate-release formulation of galantamine.

Another study compared 5 mg ALPHA-1062 delayed-release tablets with 8 mg galantamine hydrobromide ER capsules, with similar results. ■