Med Check: No Accelerated Pathway for Donanemab and More

The U.S. Food and Drug Administration (FDA) has declined to accept Eli Lilly’s Alzheimer’s biologic donanemab into the accelerated approval pathway, the company announced in January. Donanemab is a monoclonal antibody that targets beta amyloid buildup in the brain, which is thought to contribute to Alzheimer’s disease.

In its complete response letter to the accelerated approval application, the FDA specifically requested that Eli Lilly provide data from at least 100 patients who received a minimum of 12 months of continued treatment on donanemab.

The FDA had previously granted Breakthrough Therapy designation for donanemab based on the results of a phase 2 clinical trial called TRAILBLAZER-ALZ that evaluated the safety and efficacy of donanemab in patients with Alzheimer’s disease. In the trial, 257 patients with early symptomatic Alzheimer’s disease received either donanemab or placebo intravenously every four weeks for up to 72 weeks. Compared with those who received placebo, those who received donanemab experienced less cognitive and functional decline over the course of the trial, as measured by the change from baseline on the Integrated Alzheimer’s Disease Rating Scale.

Although the TRAILBLAZER-ALZ trial included more than 100 patients treated with donanemab, due to the speed of plaque reduction, many patients were able to stop dosing as early as six months of treatment, resulting in fewer than 100 patients receiving 12 months of donanemab.

 

The FDA has accepted for Priority Review a New Drug Application (NDA) for OPNT003 (nasal nalmefene) for the treatment of opioid overdose, Opiant Pharmaceuticals announced in January. Priority Review is granted to therapies that the FDA determines have the potential to provide a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious condition. OPNT003 was previously granted Breakthrough Therapy designation when a confirmatory pharmacokinetic study comparing a 3 mg spray of the drug with a 1 mg intramuscular nalmefene hydrochloride injection in 68 healthy patients revealed that OPNT003 achieved higher plasma concentrations compared with the intramuscular injection.

The NDA also included data from a second study that found similar plasma concentrations of OPNT003 whether the treatment was administered as a single dose in each nostril or as two doses in a single nostril. A third study found the drug to be noninferior to intranasal naloxone and found that nasal nalmefene produced a greater reversal of remifentanil-induced respiratory depression that was nearly twice that produced by nasal naloxone at five minutes.

 

 In January Otsuka Pharmaceutical Co., Ltd. and H. Lundbeck A/S announced that the FDA has granted Priority Review for its supplemental NDA (sNDA) for brexpiprazole for the treatment of agitation associated with Alzheimer’s dementia.

The sNDA submission includes data from two positive clinical phase 3 studies that investigated the treatment of brexpiprazole in patients with agitation related to Alzheimer’s dementia. In Study 331-12-283, 433 patients with agitation associated with Alzheimer’s took either 1 or 2 mg of brexpiprazole or placebo daily for 12 weeks. Those who took 2 mg of brexpiprazole had greater improvements in their Cohen-Mansfield Agitation Inventory (CMAI) Total Score from baseline to week 12 compared with placebo. In Study 331-14-213, which included 345 patients, patients were randomized to either 2 or 3 mg of brexpiprazole or placebo daily for 2 weeks. Those who took either dose of brexpiprazole had greater improvements in their CMAI Total Score from baseline to week 12 compared with placebo. ■