MedCheck: Valbenazine, Leqembi Autoinjector, LAI Olanzapine, and Otsuka Flop
Candidate After Phase 3 Flop
In May Otsuka Pharmaceutical Co. Ltd. announced that it had terminated development of AVP-786 (quinidine plus deuterium-modified dextromethorphan), which it had been investigating for the treatment of agitation in Alzheimer’s disease.
In February the company announced that AVP-786 did not meet its primary endpoint in a phase 3 trial. In the trial, 601 patients who had a diagnosis of probable Alzheimer’s disease and had moderate/severe agitation secondary to Alzheimer’s disease were randomized to take either low-dose or high-dose AVP-786 or placebo orally twice per day for 12 weeks. At the end of the trial, there was no statistically significant difference in the Cohen-Mansfield Agitation Inventory total score from baseline in either treatment group compared with the placebo group.
Long-Term Valbenazine Appears Effective for Tardive Dyskinesia
A phase 3 trial suggests that Ingrezza (valbenazine) can help control symptoms in patients with tardive dyskinesia for up to 48 weeks, Neurocrine Biosciences Inc. announced in May.
In the KINECT-4 study,103 patients took either 40 mg or 80 mg of Ingrezza per day for 48 weeks. At week 4, 55% of participants on the lowest starting dose (40 mg) experienced clinically meaningful improvement, defined as at least a 2-point reduction on the Abnormal Involuntary Movement Scale (AIMS) total score. Overall, 95% of participants reached this threshold by week 24, and 97% reached this threshold by week 48. Improvement in symptoms was sustained throughout treatment, with an AIMS mean total score reduction of 10.5 points from baseline to week 48. In addition, 86% of patients met the treatment response threshold of at least 50% reduction on AIMS, and 52% met the higher threshold of at least 70% reduction on AIMS at week 48.
Further, 88% of patients and 92% of health care professionals rated participants’ symptoms as “much improved” or “very much improved” at week 48, as measured by the Patient Global Impression of Change and Clinical Global Impression of Change-TD, respectively.
The study was published in the Journal of Clinical Pharmacology and is posted here.
Biologics License Application Submitted for Leqembi
In May Eisai Co. Ltd. and Biogen Inc. announced that Eisai began the rolling submission of a Biologics License Application (BLA) to the Food and Drug Administration for a subcutaneous delivery method for Leqembi (lecanemab-irmb). A BLA is a request for permission to introduce, or deliver for introduction, a biologic product into interstate commerce.
The FDA approved an intravenous formulation of lecanemab in January 2023 for the treatment of Alzheimer’s disease in patients with mild cognitive impairment or mild dementia. The BLA is based on data from the Clarity AD trial open-label extension and modeling of observed data. The data suggested that a subcutaneous injection of Leqembi clears about 14% more amyloid in the brain compared with the infused version.
If the FDA approves the BLA for the autoinjector, the device could be used to administer 360 mg lecanemab weekly to patients at home or at medical facilities after they complete the biweekly intravenous initiation phase. These weekly doses maintain drug concentrations sufficient to sustain the clearance of highly toxic protofibrils, which can continue to cause neuronal injury even after amyloid-beta plaque has been cleared from the brain.
Long-Acting Injectable Olanzapine Promising for Treating Schizophrenia
Patients with schizophrenia who were treated with TEV-‘749 (olanzapine subcutaneous extended release injection) in a phase 3 trial continued to experience reduced symptoms eight weeks after injection, Teva and Medincell announced in May.
In the SOLARIS trial, 675 adult patients with schizophrenia whose symptoms worsened in the prior two months were randomly assigned to receive a monthly high, medium, or low dose injection of TEV-‘749 or placebo. At the end of eight weeks, patients who received TEV-‘749 had a mean decrease in Positive and Negative Syndrome Scale total score from baseline to week 8 of 9.71 points, 11.27 points, and 9.71 points for the high, medium, and low dose groups, respectively, compared with those who received placebo. Those who received TEV-‘749 also had more improvement on the Clinical Global Impressions–Schizophrenia and Personal and Social Performance Scale total score than those who received placebo.
To date, there have been no reported cases of post-injection delirium/sedation syndrome in the SOLARIS trial. ■
