The promising schizophrenia drug Cobenfy will face access problems

Cobenfy (xanomeline/trospium chloride; formerly KarXT) was approved by the Food and Drug Administration in late September to treat schizophrenia in adults. The drug has a novel mechanism of action, the first for schizophrenia in several decades. Cobenfy targets cholinergic receptors rather than balancing dopamine and serotonin levels, which is the case with traditional atypical antipsychotics such as Abilify (aripiprazole) and Zyprexa (olanzapine). However, Cobenfy is likely to face challenges in accessing insurers as it is priced significantly above existing standards of care.

Schizophrenia is a chronic and disabling mental illness that affects a person’s thinking, feeling, and behavior. The disease affects approximately 2.8 million people in the United States.

Approximately one-third of patients suffer from treatment-resistant schizophrenia, meaning there is an unmet need in this therapeutic area. Cobenfy could partially fill a gap, particularly in patients who do not respond well to atypical antipsychotics because they have limited options for treating their symptoms. New data presented last week at the 2024 Psychiatry Congress suggests sustained improvement in schizophrenia symptoms with long-term treatment. In addition, in contrast to atypical antipsychotics, Cobenfy does not contain a warning about increased mortality in older patients with dementia-related psychosis or suicidal ideation when taking antidepressants at the same time.

In addition, Cobenfy’s new mechanism of action appears to be associated with fewer metabolic side effects such as weight gain and sleepiness. And in clinical trials, there have been no reports of tardive dyskinesia, or involuntary body movements caused by blockade of dopamine receptors. Tardive dyskinesia is a fairly common side effect in patients taking Zyprexa and Risperdal (risperidone).

The adverse events associated with older medications may result in lower patient adherence. However, Cobenfy requires twice-daily oral administration, a more frequent dosing regimen than the existing line of atypical antipsychotics. Therefore, it is unclear what the net impact will be on patient adherence and persistence.

Cobenfy is expected to face access challenges related to its price and evidence base for cost-effectiveness. The estimated annual cost of Cobenfy is $22,500, compared to $540 for a generic antipsychotic like Abilify. This could pose a problem for coverage and access because a panel of the Institute for Clinical and Economic Review, in its review of the evidence, voted 10 to 2 that the current evidence is sufficient to show a net health benefit in comparison to Abilify.

ICER ratings can influence payers’ decision-making regarding prescription drug coverage. It’s possible that insurers or pharmacy benefit managers will require Abilify to fail before reimbursing Cobenfy, a so-called fail-first policy.

However, ICER’s analysis contains mixed results. A majority of ICER panelists (7-5) who assessed the evidence considered it sufficient to demonstrate a net health benefit compared to Zyprexa or Risperdal. And ICER gave a price range of between $16,000 and $20,000 per year, which would reflect the expected clinical benefit. This is relatively close to the list price of $22,500. Discounts and rebates may keep the net price of Cobenfy within the acceptable price range suggested by ICER.

Still, ICER’s Technology Assessment Panel votes raise some doubts about Cobenfy’s cost-effectiveness compared to current treatment options.

At least two-thirds of patients with schizophrenia are on Medicaid, the federal 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 reimburse the government at least 23.1% of the average manufacturer price. In return, Medicaid must include FDA-approved drugs from these manufacturers.

However, plans that manage the pharmacy benefit may still impose coverage limits, including utilization management tools such as: E.g., prior authorization, fail-first policy requirements, and therapy duration limits. Accordingly, Cobenfy is unlikely to be a first-line treatment option for most patients. Rather, it is likely to be an option for patients who have a poor or partial response to atypical antipsychotics or who cannot tolerate the side effects of weight gain, sedation, and movement disorders associated with atypical antipsychotics.

The competitive dynamics in the schizophrenia space are likely to bring changes that create opportunities and challenges for Cobenfy’s sponsor Bristol Myers Squibb. The company aims to expand the product’s reach by exploring new indications, including the use of Cobenfy as an add-on therapy for schizophrenia patients who do not respond adequately to their current atypical antipsychotic medications, as well as testing for bipolar disorder and agitation, which are often associated with Alzheimer’s disease. At the same time, Cobenfy may eventually face competition, including from emraclidine, a novel once-daily drug being studied in Phase 2 for schizophrenia and Alzheimer’s psychosis.