Schizophrenia and split personality disorder.
Cobenfy (xanomeline/trospium chloride; formerly KarXT) was approved for schizophrenia in adults by the Food and Drug Administration in late September. The drug has a novel mechanism of action, which is the first for schizophrenia in several decades. Cobenfy targets cholinergic receptors instead of balancing levels of dopamine and serotonin, which is what conventional atypical antipsychotics do, such as Abilify (aripiprazole) and Zyprexa (olanzapine). But insurer access challenges likely lie ahead for Cobenfy given its considerably higher price than existing standards of care.
Schizophrenia is a chronic and disabling mental illness affecting how a person thinks, feels and behaves. Roughly 2.8 million people in the United States are afflicted with the disease.
Around one third of patients have treatment-resistant schizophrenia, which implies that there’s unmet need in this therapeutic area. Cobenfy may partially fill a void, particularly for those patients who do not respond well to atypical antipsychotics as they have limited options to manage their symptoms. New data presented last week at the 2024 Psych Congress suggests continued improvements in symptoms of schizophrenia with long-term treatment. Additionally, unlike the atypical antipsychotics, Cobenfy does not have a boxed warning of increased mortality in elderly patients with dementia-related psychosis or suicidal ideation with concomitant antidepressant drug usage.
Moreover, Cobenfy’s new mechanism of action appears to be associated with fewer metabolic side effects such as weight gain and drowsiness. And in clinical trials there have been no reports of tardive dyskinesia, or involuntary body movements caused by the blockade of dopamine receptors. Tardive dyskinesia is a fairly common side effect for patients taking Zyprexa and Risperdal (risperidone).
The adverse events related to older medications can lead to less patient persistence. However, Cobenfy requires twice-daily oral administration, a more frequent dosing regimen than the existing set of atypical antipsychotics. As such, it’s unclear what the net effect on patient adherence and persistence will be.
Cobenfy is expected to face access challenges having to do with its price and the evidence base for cost-effectiveness. The estimated yearly cost for Cobenfy is $22,500, compared to $540 for a generic antipsychotic such as Abilify. This could present a problem for coverage and access given that in its review of the evidence, an Institute for Clinical and Economic Review panel voted 10-2 that the current evidence is adequate to show a net health benefit when compared to Abilify.
ICER assessments can inform payers’ decision-making with respect to coverage of prescription drugs. It’s possible that insurers or pharmacy benefit managers will require failure on Abilify before Cobenfy is reimbursed, a so-called fail-first policy.
This said, ICER’s analysis contains mixed results. A majority of ICER panelists (7-5) assessing the evidence found it adequate to demonstrate a net health benefit when compared to Zyprexa or Risperdal. And ICER posted a price range of between $16,000 and $20,000 per year that would align with the expected clinical benefit. This is relatively close to the list price of $22,500. With discounting and rebates, Cobenfy’s net price may fall within ICER’s proposed acceptable price range.
Even so, ICER’s technology evaluation panel votes leave some doubt with respect to Cobenfy’s cost-effectiveness relative to current treatment options.
At least two-thirds of patients with schizophrenia are on Medicaid, the federal-state program that helps cover medical costs for people with limited income and resources. Under the Medicaid rebate program, manufacturers who want their drugs covered must rebate at least 23.1% of the average manufacturer price to the government. In return, Medicaid has to include the FDA-approved drugs made by those manufacturers.
However, plans that manage the pharmacy benefit can still institute coverage restrictions, including utilization management tools, such as prior authorization, fail-first policy requirements and duration of therapy limits. Accordingly, for most patients, Cobenfy probably won’t be a first-line treatment option. Instead, it is expected to be an option for patients who have a poor or partial response to atypical antipsychotics or those who cannot tolerate the side effects of weight gain, sedation, and movement disorders associated with atypical antipsychotics.
Competitive dynamics in the schizophrenia space will presumably bring about changes that offer opportunities and pose challenges to Cobenfy’s sponsor, Bristol Myers Squibb. The company is looking to augment the product’s reach as it investigates new indications, including use of Cobenfy as add-on therapy for schizophrenia patients who aren’t adequately responding to their current atypical antipsychotics and testing for both bipolar disorder and agitation that often accompanies Alzheimer’s disease. At the same time, Cobenfy could eventually face competition, including the therapeutic emraclidine which is a once-daily novel agent being investigated in phase 2 for schizophrenia and Alzheimer’s disease psychosis.
