Med Check: Clozapine REMS; Aduhelm; BNC210 Fast Tracked for Social Anxiety Disorder; and More

Aduhelm Shows Promise for Alzheimer’s Disease

Two phase 3 clinical trials of Aduhelm (aducanumab) showed a correlation between plasma p-tau reduction and less cognitive and functional decline in patients with Alzheimer’s disease, Biogen and Esai announced last November. The accumulation of the protein tau inside neurons leads to neurofibrillary tangles—a pathological hallmark of Alzheimer’s disease.

The reductions in plasma p-tau were also correlated with a lowering of amyloid beta plaque, which is thought to play a role in the development of Alzheimer’s.

An independent laboratory analyzed approximately 7,000 plasma samples from more than 1,800 patients in the EMERGE and ENGAGE trials. In the EMERGE trial, p-tau decreased 13% from baseline in the high-dose group and rose 8% in the placebo group. In the ENGAGE trial, p-tau decreased 16% from baseline in the high-dose group and rose 9% in the placebo group. In both trials, decreased p-tau was associated with less decline on the Clinical Dementia Rating Sum of Boxes Score, the Mini-Mental State Examination, the Alzheimer’s Disease Assessment Scale–Cognitive Subscale, and the Alzheimer’s Disease Cooperative Study/Activities of Daily Living scale adapted for MCI.

Aduhelm was approved by the FDA in June to treat Alzheimer’s disease.

BNC210 Fast Tracked for Social Anxiety Disorder

Last December the U.S. Food and Drug Administration (FDA) granted fast track designation to BNC210 for the acute treatment of social anxiety disorder and other anxiety-related disorders, Bionomics Limited announced. The FDA fast track is a process designed to facilitate the development of drugs that treat serious conditions and fill an unmet medical need and to expedite their review.

A previous in-clinic phase 2a study in patients with generalized anxiety disorder found that a single dose of the drug in liquid form showed significant anti-anxiety signals as measured in brain imaging and behavioral studies, but without evidence of sedating patients or becoming addictive.

A randomized, double-blind, multicenter phase 2 trial of the drug is now underway. Patients with anxiety disorder will take a single oral dose of either the drug or placebo an hour before an anxiety-provoking task (for example, being asked to speak on a topic) and then use the Subjective Units of Distress Scale to report on the anxiety levels they experienced during the task.

Phase 2 Study Suggests COMP360 Psilocybin Effective for Depression

A phase 2 trial suggests that COMP360 (psilocybin) may be a useful therapy for patients with treatment-resistant depression, Compass announced last November.

The trial included 233 patients were randomized to take a single dose of 1 mg, 10 mg, or 25 mg of COMP360 psilocybin. All patients had discontinued antidepressants before the trial, and they received psychological support from specially trained therapists during the trial. The primary outcome was a decrease in the Montgomery–Åsberg Depression Rating Scale (MADRS).

At week 3, 36.7% of patients in the 25 mg group experienced improvements on the MADRS compared with 17.7% of patients in the 1 mg group. In addition, 29.1% of patients in the 25 mg group were in remission (defined as MADRS total score ≤10) compared with 7.6% of patients in the 1 mg group. Those in the 10 mg group did not have a statistically significant difference in response at week 3 compared with those in the 1 mg group.

At week 12, 24.1% of patients in the 25 mg group continued to respond to treatment compared with 10.1% of patients in the 1 mg group.

OPNT003 Fast Tracked for Opioid Overdose

Last November the FDA granted fast track designation to OPNT003 (nasal nalmefene), an investigational treatment for opioid overdose, Opiant Pharmaceuticals announced. The drug is being investigated as an alternative to naloxone.

Previously, OPNT003 was evaluated in a confirmatory pharmacokinetic study that compared a 3 mg spray of the drug with a 1 mg intramuscular nalmefene hydrochloride injection in 68 healthy patients. The study revealed that OPNT003 achieved higher plasma concentrations compared with the intramuscular injection

FDA Temporarily Suspends Some Clozapine REMS Program Requirements

The Food and Drug Administration (FDA) has temporarily suspended certain requirements of the recently modified Clozapine Risk Evaluation and Mitigation Strategy (REMS) Program after the agency received reports of challenges with the program. The Clozapine REMS is a safety program required by the FDA to manage patients’ risk of neutropenia associated with clozapine treatment.

“Health care professionals continue to alert FDA about ongoing difficulties with the Clozapine REMS program, including a high call volume and long call wait times for stakeholders since launch of the program on November 15,” the FDA wrote in a statement. “We understand that this has caused frustration and has led to patient access issues for clozapine. … Continuity of care, patient access to clozapine, and patient safety are our highest priorities. We are working closely with the Clozapine REMS program administrators to address these challenges and avoid interruptions in patient care.”

The temporary changes mean that pharmacists may dispense clozapine without REMS dispense authorization and wholesalers may continue to ship clozapine to pharmacies and health care settings without confirming REMS enrollment.

Patients who abruptly stop using clozapine can experience significant physical and behavioral symptoms, including the potential re-emergence of psychosis.

Cerezen Device Granted Breakthrough Status for Alzheimer’s Cognitive Impairment

In November the FDA granted Breakthrough Device designation status to Renew Bioscience’s Cerezen Device, a novel treatment for mild cognitive impairment due to Alzheimer's disease and mild dementia of the Alzheimer's type. The goal of the FDA Breakthrough Device Program is to provide patients and health care providers with timely access to medical devices by speeding up their development, assessment, and review.

The device is designed to simulate the physiological effects of vigorous exercise and stimulate endothelial cell function, with the goal of bringing more oxygenated blood to the body and brain. It uses external counterpulsation therapy to enhance blood flow and overall vascular efficiency. During treatment, a technician wraps inflatable cuffs that are similar to blood pressure cuffs around the patient's calves, thighs, and hips. The cuffs then synchronize to inflate and deflate between heartbeats.

Zimhi Approved for Opioid Overdose

In October the FDA approved Zimhi (naloxone hycrochloride) injection by Adamis Pharmaceuticals Corp. for the emergency treatment of known or suspected opioid overdose. Zimhi is administered using a single-dose, prefilled syringe that delivers 5 mg of naloxone hydrochloride solution through intramuscular or subcutaneous injection. This dose is greater than previously approved injectable naloxone products in the 0.4 mg and 2 mg doses.

Zimhi is intended to be administered by people who are at least 12 years old because children younger than that may not have the hand strength required to operate the syringe correctly. The injection is designed to be injected in the thigh.

Zimhi received approval through the 505(b)(2) approval pathway under the Federal Food, Drug, and Cosmetic Act. A new drug application submitted through this pathway may rely on the FDA’s finding that a previously approved drug is safe and effective or on published literature to support the safety and/or effectiveness of the proposed product, if such reliance is scientifically justified. Adamis submitted a 505(b)(2) application that relied, in part, on the FDA’s finding of safety and effectiveness for Narcan (naloxone hydrochloride) injection to support approval.

Vraylar May Help Symptoms of Major Depressive Disorder

A phase 3 trial suggests that Vraylar (cariprazine) may be useful as an adjunct therapy for the treatment of major depressive disorder (MDD), AbbVie announced in October. Vraylar is currently approved for treating adults with schizophrenia, adults with manic or mixed episodes associated with bipolar I disorder, and adults with depressive episodes associated with bipolar I disorder.

In the study, 759 adult patients with MDD who did not adequately respond to treatment with a single antidepressant were randomized to one of three possible treatment arms: cariprazine 1.5 mg orally once daily, cariprazine 3 mg once daily, or placebo. All patients continued taking their current antidepressant.

From baseline to week six, patients who took either dose of cariprazine had greater improvements in their symptoms compared with patients who took placebo, as measured by the Montgomery-Åsberg Depression Rating Scale total score.

Oxytocin Fails to Improve Social Functioning in Youth With Autism

Taking oxytocin, a hormone associated with empathy and social bonding, does not appear to improve social functioning among children with autism spectrum disorder (ASD), suggests a study in the New England Journal of Medicine. The findings contradict those of earlier reports.

In the study, 277 patients aged 3 to 17 years who had ASD were randomized to receive 48 I.U. of oxytocin via nasal spray or placebo daily for 24 weeks. During the study, the patients’ caregivers rated them on a questionnaire, the Aberrant Behavior Checklist modified Social Withdrawal subscale, which measures irritability, social withdrawal, and other behaviors associated with ASD. At the end of the study, the differences between the two groups’ baseline and final scores did not differ significantly. ■