Med Check: Aduhelm, Deep Brain Stimulation System, Narcan and More

In January Biogen announced that it will stop both the sale and study of Aduhelm (aducanumab-avwa) 100 mg intravenous injection for the treatment of Alzheimer’s disease. As part of this change, the company is terminating the ENVISION clinical trial.

The U.S. Food and Drug Administration (FDA) approved Aduhelm in June 2021 via the agency’s fast-track accelerated approval program. Fast-tracking is designed to speed up the approval of medications for serious or life-threatening illnesses by allowing companies to provide a surrogate endpoint that reasonably predicts future clinical benefit. In Aduhelm’s case, the surrogate endpoint was evidence that people who took the medication had significantly greater reduction of amyloid beta plaques in their brains after 78 weeks than those who took placebo. However, many experts have argued that amyloid plaques are a poor biomarker for the disease, and there is little evidence that amyloid causes any of the cognitive and behavioral symptoms of Alzheimer’s.

According to the announcement, in January 2023 Biogen began a strategic review of its research and development efforts and sought potential partners or external financing for Aduhelm, without success. The company is now shifting resources that had been devoted to Aduhelm to advance another FDA-approved Alzheimer’s drug, Leqembi (lecanemab-irmb) and investigate other treatments for the disease.

In January the FDA approved the marketing of the Liberta RC deep brain stimulation system for patients who have movement disorders, Abbot announced.

The device is approved as an adjunctive therapy to reduce some of the symptoms of advanced levodopa-responsive Parkinson’s disease that are not adequately controlled by medications. It is also approved for the suppression of disabling upper extremity tremor in adult essential tremor patients whose tremor is not adequately controlled by medications and the tremor constitutes a significant functional disability.

According to press materials released by the company, the Liberta RC system is the smallest rechargeable deep brain stimulation device with remote programing, about the height and width of a smartwatch face. When used under standard settings, the system needs to be recharged about 10 times a year, but patients may also recharge it once a week for 30 minutes.

Ensysce Biosciences announced in January that the FDA has given Breakthrough Therapy designation to PF614-MPAR, an oral opioid medication designed to have overdose protection. The FDA’s Breakthrough Therapy designation expedites the development and review of drugs for serious conditions.

PF614-MPAR is a prodrug of oxycodone that can be activated only by the enzyme trypsin, which is found in the small intestine. Further, PF614-MPAR includes a trypsin inhibitor that blocks the activation and release of the opioid when a patient takes too much of the medication. A Phase 1 trial showed that a 25 mg dose of PF614-MPAR delivered oxycodone as designed when patients took a prescribed dose of one to two capsules. However, when patients took three or more capsules simultaneously, the amount of opioid released and absorbed into the circulation diminished compared with PF614 that did not have overdose protection built into the medication.

The FDA announced in January that it has approved a shelf-life extension for Narcan (naloxone 4 mg) nasal spray by Emergent BioSolutions. The shelf life of these products has been extended from three years to four years.

The shelf-life extension applies only to Narcan 4 mg nasal spray products produced after January 18. The shelf life of products that were produced and distributed before the FDA’s announcement remains unchanged. The FDA advised prescribers, patients, and caregivers to continue to abide by the expiration date printed on each product’s packaging and within the product’s labeling.

The FDA has rejected the New Drug Application (NDA) for Satsuma’s STS101 (dihydroergotamine nasal powder) for the acute treatment of migraine, Satsuma’s parent company Shin Nippon Biomedical Laboratories announced in January. In its Complete Response Letter, the FDA noted that the reasons for the rejection relate to chemistry, manufacturing, and controls considerations. The FDA did not request any new clinical trials to support approval of the drug.

The FDA accepted the NDA for STS101 in May 2023 based on data from the Phase 3 ASCEND trial, in which 446 patients received more than 10,500 doses of STS101 or STS101-MK2 (the same medication in an updated nasal delivery device) over 18 months. Among the 172 patients who exclusively took STS101-MK2, the drug relieved pain and the most bothersome symptoms in 34.2% and 53.4% of all treated migraine attacks, respectively, within two hours of treatment. It also eliminated the need for rescue medications in 94% of treated attacks. ■