Med Check: Updates to Clozapine REMS, Weekly Treatment for OUD, and More

FDA Updates Clozapine REMS

In July the Food and Drug Administration (FDA) approved modifications to the Clozapine Risk Evaluation and Mitigation Strategy (REMS). Several of these changes affect health professionals who prescribe clozapine.

Beginning on November 15, the Clozapine REMS requires a New Patient Status Form to document monitoring for all outpatients. This form must be submitted monthly.

All health professionals who prescribe clozapine must be recertified by November 15 to continue prescribing the medication and they must re-enroll their patients who will continue taking the medication. Patients who are not re-enrolled by November 15 will no longer be able to receive clozapine.

Information on recertifying and re-enrolling in the Clozapine REMS is posted here

Weekly OUD Treatment Gets Fast Track Designation

Lyndra Therapeutics’ investigational weekly treatment for opioid use disorder (OUD), LYN-014, has received a fast track designation from the FDA, the company announced in July. LYN-014 is an oral, ultra-long-acting, extended-release levomethadone capsule. 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 expedite their review.

Levomethadone, is an enantiomer of racemic methadone (its molecules are a mirror image of those in racemic methadone). Levomethadone is not approved for use in the United States, although it has been approved for use in Europe since the 1960s for pain management and medication treatment for OUD.

In April the FDA granted LYN-014 Investigational New Drug status, which enabled Lyndra to initiate a phase 1 clinical trial in patients whose OUD is currently controlled on daily oral immediate-release methadone.

FDA Grants Breakthrough Therapy Designation to Investigational Narcolepsy Treatment

In July Takeda Pharmaceutical Co. Ltd. announced that the FDA granted Breakthrough Therapy designation to TAK-994, the company’s investigational oral orexin agonist for the treatment of excessive daytime sleepiness in patients with narcolepsy type 1. The FDA’s Breakthrough Therapy designation expedites the development and review of drugs for serious conditions. The criteria for Breakthrough Therapy designation require preliminary clinical evidence that indicate that the drug may demonstrate substantial improvement over available therapy on at least one clinically significant endpoint.

According to a statement by Takeda, the FDA’s decision to grant the Breakthrough Therapy designation was based in part on early phase and preliminary clinical data suggesting that the drug demonstrates substantially improved objective and subjective measurements of daytime wakefulness in patients with narcolepsy type 1.

FDA to Review Diazepam Buccal Film

The FDA will review Libervant (diazepam) buccal film for the treatment of acute uncontrolled seizures in patients with refractory epilepsy on stable regimens of antiepileptic drugs, Aquestive Therapeutics announced in July.

A phase 1/2 open-label trial of 31 patients with seizure disorders who took antiepileptic drugs found that treatment with Libervant resulted in similar systemic exposures to Diastat diazepam rectal gel, the standard treatment.

Aquestive originally submitted a New Drug Application (NDA) for Libervant in February 2020, but in September 2020 the FDA issued a Complete Response Letter stating that the study showed a lower drug exposure level than desired in certain weight groups. The letter also noted a number of protocol deviates in blood draws in one of the studies that was included in the NDA. In response, the company provided additional analysis as part of the NDA submission now under FDA review.

Kloxxado Now Available to Treat Opioid Overdose

Hikma Pharmaceuticals PLC’s nasal spray Kloxxado (naloxone hydrocloride) for the emergency treatment of opioid overdose is now available, the company announced in August. Kloxxado, which was approved by the FDA in April, delivers 8 mg of naloxone directly into the nasal cavity. The FDA had previously approved 2 mg and 4 mg naloxone nasal spray products.

The FDA approved Kloxxado based on previous findings about the safety and effectiveness of Narcan injection (naloxone hydrochloride) for treating opioid overdose. Hikma Pharmaceuticals also submitted its own safety and effectiveness data. ■