Med Check: Atuzaginstat and Alzheimer’s Disease; Blood Cytokine Test and Suicidal Ideation; FDA and Dsuvia; Gocovri and Parkinson’s Disease

In February the Food and Drug Administration (FDA) placed a partial clinical hold on Cortexyme Inc.’s investigational Alzheimer’s drug atuzaginstat because of adverse liver events reported by some participants taking the medication. Under the partial hold, no new participants will be enrolled in the open-label extension phase of Cortexyme’s ongoing phase 2/3 trial, which is evaluating the efficacy, safety, and tolerability of the drug in patients with mild to moderate Alzheimer’s disease. Participation will also be discontinued for patients who are currently enrolled in the open-label extension.

The 643 patients who are enrolled in the double-blind, placebo-controlled randomized phase 2/3 trial will continue to receive the drug at their assigned dose. The adverse liver events have been reversible and without any known long-term effects on the patients in the trial, the company said in a statement.

Campbell Neurosciences Inc. has successfully completed a 30-patient clinical trial to assess blood levels of an inflammatory cytokine as a predictor for suicidal ideation, the company announced in February.

There were three groups of patients in the trial: 10 with no history of personal or family psychiatric history and no suicide attempts, 10 with suicidal ideation as determined by a Hamilton Depression Rating Scale suicide item of greater than 2, and 10 with suicidal ideation who attempted suicide in the last six months. Those in the first group had a mean of 7.6 picograms of cytokine per milliliter of blood (pg/ml), whereas those in the second group had a mean of 28.9 pg/ml and those in the third group had a mean of 45.8 pg/ml.

In February the FDA issued a warning letter to AcelRx Pharmaceuticals Inc. for disseminating false and misleading promotional communications regarding Dsuvia (sufentanil sublingual tablet). The drug is used to treat acute pain in adults that is severe enough to require an opioid analgesic but for which alternative treatments are inadequate. It is used in medically supervised health care settings such as hospitals, surgical centers, and emergency departments.

The warning letter noted that a banner ad and a tabletop display with the catchphrase “Tongue and Done” are misleading because they imply that administering the drug requires only one simple step when in fact the prescribing information outlines a multistep process. The prescribing information requires that the health care professional visually confirm the tablet’s placement in the sublingual space of the patient’s mouth and to remove and dispose of the tablet if it is not.

“The multiple steps involved in the administration of Dsuvia reflect the complexity of use of Dsuvia,” the agency said in a statement. “Given the potency and the small size of the tablet, the risk of misplaced tablets is a serious safety concern to the patient and others ... Therefore, by oversimplifying the administration process, these presentations create a misleading impression about the safe administration of Dsuvia. These presentations are particularly concerning considering a REMS program was required for Dsuvia to ensure that the benefits of the drug outweigh the risk of respiratory depression that can result from accidental exposure.”

The warning letter also noted that the banner ad mentions dosing intervals but neglects to state the maximum number of tablets that should be administered in a 24-hour period.

Gocovri (amantadine), Adamas Pharmaceuticals Inc.’s drug for treating dyskinesia in patients with Parkinson’s disease (PD) who receive levodopa-based treatment, now has a second indication: In February it won FDA approval as an adjunctive treatment to levodopa/carbidopa in patients with PD who are experiencing “off” episodes. During off episodes, motor symptoms like stiffness or tremor return even though the patient is taking medication for PD.

In two placebo-controlled phase 3 clinical trials that evaluated the efficacy and safety of Gocovri for the treatment of dyskinesia, 198 patients with PD who were experiencing off episodes received either 274 mg of the drug once per day or placebo. At 12 weeks, patients who took Gocovri experienced significantly less off time and dyskinesia compared with those who took placebo. ■