Bristol Myers Squibb’s highly anticipated schizophrenia drug KarXT is fast approaching a September deadline for the Food and Drug Administration to decide on approval. Yet competition already looms for a market that’s estimated to soon be worth billions of dollars.
KarXT, a so-called muscarinic agonist, may become the first new kind of schizophrenia drug in decades. Close behind it is AbbVie’s emraclidine, which works in a similar fashion.
People with schizophrenia experience a broad range of symptoms, from hallucinations and delusions to cognitive impairments and social withdrawal. Clinical testing has shown that, like KarXT, emraclidine, which AbbVie acquired from Cerevel Therapeutics in a multibillion-dollar deal, is effective at controlling symptoms without the debilitating side effects or drawbacks of traditional antipsychotics, which cause almost three-quarters of patients to abandon treatment.
But experts say once-daily dosing versus twice-daily treatment, and a potentially more gut-friendly formulation, may give emraclidine an edge over KarXT, which Bristol Myers Squibb acquired in a $14 billion acquisition of Karuna Therapeutics.
Emraclidine is designed to reduce the excess dopamine signaling that causes schizophrenic symptoms, but without blocking the receptors altogether. By blocking specific “M4” receptors, rather than others more broadly, the drug could help patients deal with symptoms without the side effects that come with less precise treatment.
A Phase 1b study found people who received emraclidine for six weeks saw statistically significant improvements on a standardized scale of symptom severity without side effects like weight gain, restlessness and movement disorders.
“By selectively targeting the M4 receptor, emraclidine resulted in infrequent gastrointestinal side effects, with rates similar to placebo,” Dawn Carlson, AbbVie’s vice president of neuroscience development, wrote in an email.
AbbVie is testing the drug in two mid-stage trials that support approval, and expects to release topline data later this year.
According to Carlson, the Cerevel acquisition, finalized this month, not only gave AbbVie emraclidine but several preclinical and clinical-stage drugs that fit into the pharma giant’s existing portfolio.
“There are multiple programs in Cerevel’s pipeline across several psychiatric and neurological conditions such as schizophrenia, Parkinson’s disease and mood disorders, where there continues to be significant unmet need for patients,” she wrote.
Emraclidine may also have applications outside of schizophrenia for dementia-related psychosis in diseases like Alzheimer's and Parkinson’s.
Several other new schizophrenia drugs are advancing through testing. While many have the same dopamine or serotonin targets as traditional antipsychotics, others rely on novel approaches like KarXT and emraclidine.
Neurocrine Biosciences is testing a muscarinic agonist in a Phase 2 study with Nxera Pharma. The company also has another mid-stage schizophrenia candidate called luvadaxistat. Boehringer Ingelheim is in Phase 3 with its drug iclepertin, a selective glycine transporter 1 inhibitor.
Meanwhile, Terran Biosciences is looking to compete with a prodrug therapy that’s meant to improve on KarXT’s twice-daily dosing schedule with a once-daily pill. It’s also developing a long-acting injection, dubbed TerXT LAI.
It’s unclear how either KarXT or emraclidine might compare to these investigational drugs. AbbVie has yet to conduct any head-to-head studies comparing emraclidine to other potential therapies.
An increasingly competitive market may create hurdles for drug companies, but it could create new options for people with schizophrenia. The condition affects less than 1% of the population, but is among the top 15 leading causes of disability worldwide.
“There remains a significant unmet need for more therapies with different mechanisms of action in the treatment of schizophrenia,” Carlson wrote.
