Bristol Myers' Schizophrenia Drug Nears Approval; AbbVie and Rivals Aim to Compete

Bristol Myers Squibb's eagerly awaited schizophrenia drug, KarXT, is nearing a pivotal decision point in September when the Food and Drug Administration (FDA) will decide on its approval. However, the drug faces imminent competition in a market projected to be worth billions of dollars in the near future. KarXT, known as a muscarinic agonist, may become the first novel treatment for schizophrenia in decades. Hot on its heels is AbbVie's emraclidine, which operates similarly.

Schizophrenia manifests through a variety of symptoms including hallucinations, delusions, cognitive impairments, and social withdrawal. Clinical trials have demonstrated that both KarXT and emraclidine effectively manage these symptoms without the severe side effects typical of conventional antipsychotics, which lead almost 75% of patients to discontinue treatment. Experts suggest that emraclidine might have an advantage over KarXT due to its once-daily dosing regimen and potentially more stomach-friendly formulation. AbbVie secured emraclidine through a multibillion-dollar acquisition from Cerevel Therapeutics, while KarXT was acquired by Bristol Myers Squibb through a $14 billion purchase of Karuna Therapeutics.

Emraclidine is aimed at reducing excessive dopamine signaling that leads to schizophrenic symptoms, but it achieves this without fully blocking receptors. By specifically targeting M4 receptors, the drug can help manage symptoms without the adverse effects associated with less precise treatments. A Phase 1b study indicated that patients on emraclidine for six weeks showed significant improvements in symptom severity without experiencing side effects like weight gain, restlessness, or movement disorders. The drug's selective targeting of the M4 receptor also resulted in fewer gastrointestinal issues, with side effect rates similar to those of a placebo, according to Dawn Carlson, AbbVie's vice president of neuroscience development.

AbbVie is currently testing emraclidine in two mid-stage trials that could support its approval, with top-line data expected to be released later this year. The recent acquisition of Cerevel not only provided AbbVie with emraclidine but also a range of other preclinical and clinical-stage drugs that complement the company's existing portfolio. These include treatments for various psychiatric and neurological conditions, such as Parkinson's disease and mood disorders, which represent areas of substantial unmet need.

Beyond schizophrenia, emraclidine might also be applicable to dementia-related psychosis in diseases like Alzheimer's and Parkinson's. Several other new schizophrenia treatments are progressing through clinical trials. While many target the same dopamine or serotonin pathways as traditional antipsychotics, some, like KarXT and emraclidine, employ novel mechanisms. Neurocrine Biosciences, for instance, is testing a muscarinic agonist in a Phase 2 study with Nxera Pharma and has another mid-stage candidate called luvadaxistat. Boehringer Ingelheim is in Phase 3 trials with iclepertin, a selective glycine transporter 1 inhibitor.

Meanwhile, Terran Biosciences aims to compete with a prodrug therapy designed to improve on KarXT's twice-daily dosage by offering a once-daily pill. The company is also developing a long-acting injection called TerXT LAI.

The comparative effectiveness of KarXT and emraclidine against these emerging treatments remains unclear as AbbVie has yet to conduct head-to-head studies. The increasingly competitive market poses challenges for pharmaceutical companies but could offer new treatment options for people with schizophrenia. This condition, which affects less than 1% of the global population, ranks among the top 15 leading causes of disability worldwide. There remains a significant unmet need for therapies with novel mechanisms of action to better address the treatment of schizophrenia, Carlson noted.