Med Check

In March Allergan announced that phase 3 studies of rapastinel as an adjunctive treatment for major depressive disorder (MDD) did not meet its primary endpoints.

In two studies totaling 872 patients with MDD, participants were randomized to 450 mg of rapastinel or placebo given once weekly as a bolus intravenous injection in addition to an oral antidepressant to which the patient had not responded adequately. A similar, third study of 638 participants included a third treatment arm that evaluated how patients responded to 225 mg of rapastinel. The primary endpoint for all three studies was a change in scores on the Montgomery-Åsberg Depression Rating Scale from baseline at the end of three weeks. In all three trials, scores for patients receiving rapastinel did not significantly differ from placebo.

Allergan is conducting a global phase 3 trial to evaluate rapastinel’s efficacy, safety, and tolerability as a monotherapy for MDD compared with placebo. It also is conducting a phase 2 proof-of-concept study evaluating efficacy, safety, and tolerability of rapastinel compared with placebo in addition to standard of care for patients with MDD at imminent risk of suicide.

The Food and Drug Administration (FDA) has accepted for review a New Drug Application (NDA) submitted for the investigational insomnia drug lemborexant by Eisai Co. Ltd. and Imbrium Therapeutics L.P. The companies announced the forthcoming review in March.

The NDA submission is based on data from two phase 3 clinical trials in adults with insomnia disorder. SUNRISE 1 evaluated the efficacy and safety of lemborexant versus placebo and versus an active comparator (zolpidem tartrate extended release) in 1,006 patients aged 55 years and older. SUNRISE 2 evaluated the long-term efficacy and safety of lemborexant in 949 patients aged 18 to 88 years. In both studies, lemborexant met its endpoints of improving sleep latency and efficiency.

Lemborexant is thought to work by blunting wakefulness without impeding the ability to awaken in response to external stimuli.

A multicenter phase 2 trial of trofinetide showed statistically significant improvements in three key measures of Rett syndrome compared with placebo, researchers reported April 16 in Neurology.

Trofinetide, in development by Acadia Pharmaceuticals and Neuren Pharmaceuticals Limited, is a novel synthetic analogue of neurotrophic tripeptide.

In the phase 2 study, 82 girls aged 5 to 15 years were randomized to receive liquid trofinetide or placebo orally or via gastrostomy tube twice a day for six weeks: 24 were assigned to placebo, 15 to 50 mg/kg trofinetide, 16 to 100 mg/kg trofinetide, and 27 to 200 mg/kg trofinetide. Trofinetide demonstrated statistically significant evidence of improvement at the twice-daily 200 mg/kg dose on a key caregiver assessment, the Rett Syndrome Behaviour Questionnaire, as well as two clinician assessments, the Clinical Global Impression Scale-Improvement and the RTT-Clinician Domain Specific Concerns-Visual Analog Scale.

Acadia plans to initiate a 12-week phase 3 study evaluating trofinetide in the second half of this year to evaluate trofinetide’s efficacy and safety in approximately 180 patients aged 5 to 20 years with Rett syndrome.

In March Innovative Neurological Devices launched Cervella, a cranial electrotherapy stimulator, for treating insomnia, anxiety, and depression. The device, which is approved by the FDA and requires a prescription, transmits small pulses of electric current across a patient’s brain via a pair of conductive electrodes in the ear pads of over-ear, noise-canceling headphones. Treatments typically last 30 minutes, and patients can listen to music through the headphones.

Cervella is powered by an internal rechargeable battery. Patients use an app to adjust the intensity level, frequency, and duration of treatment. Patients can store their treatment history on the app to share with health care professionals. Cervella costs $695 and the app is free.

In March Biogen and Eisai announced the discontinuation of the phase 3 ENGAGE and EMERGE trials of aducanumab for the treatment of mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease dementia. The companies decided to stop the trials after a futility analysis by an independent data monitoring committee indicated that aducanumab would most likely not meet the primary endpoints in the trials.

The companies are also discontinuing the EVOLVE phase 2 safety study and the long-term extension of the PRIME phase 1b study of aducanumab. However, they will assess the initiation of the aducanumab phase 3 secondary prevention trial as data from ENGAGE and EMERGE are further evaluated.

A study in the Journal of Clinical Pharmacology has found that the FDA-approved device for nasal administration of naloxone yielded higher plasma concentration of naloxone than improvised devices often used by first responders and the public. The improvised devices consist of a prefilled naloxone syringe attached to a mucosal atomization device.

In a study of 30 patients, researchers from the National Institute on Drug Abuse compared plasma concentrations of naloxone when it was administered once using the FDA-approved Narcan 2-mg and 4-mg nasal spray devices and the Evzio 2-mg autoinjector. They compared the results from these devices with the results obtained from administering 2 mg of naloxone either once or twice with the improvised device.

They found that it would take six administrations of naloxone via the improvised nasal device to reach the naloxone blood levels that can be achieved with one spray of the nasal Narcan brand product. ■