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 new mechanism of action, the first in decades for schizophrenia. Cobenfy targets cholinergic receptors instead of balancing the levels of dopamine and serotonin, which is what conventional atypical antipsychotics do, such as Abilify (aripiprazole) and Zyprexa (olanzapine). But for Cobenfy, challenges likely lie in access to insurers, given the significantly higher price than existing standards of care.
Schizophrenia is a chronic and disabling mental illness that affects how a person thinks, feels and behaves. About 2.8 million people in the United States suffer from the disease.
Approximately one third of patients have treatment-resistant schizophrenia, implying an unmet need in this therapeutic area. Cobenfy may partially fill a gap, especially in patients who do not respond well to atypical antipsychotics because they have limited options to control their symptoms. New facts presented last week at the 2024 Psych Congress, suggests that symptoms of schizophrenia continue to improve with long-term treatment. Furthermore, unlike atypical antipsychotics, Cobenfy does not have a boxed warning for increased mortality in elderly patients with dementia-related psychosis or suicidal ideation when used concurrently with antidepressants.
Furthermore, Cobenfy’s novel 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 in patients taking Zyprexa and Risperdal (risperidone).
The side effects associated with older medications can lead to less patient persistence. However, Cobenfy requires twice-daily oral administration, a more frequent dosing schedule than the existing set of atypical antipsychotics. As such, it is unclear what the net effect on patient compliance and persistence will be.
Cobenfy is expected to gain access challenges related to price and the scientific basis for cost-effectiveness. The estimated annual costs for Cobenfy are: $22,500compared to $540 for a generic antipsychotic like Abilify. This could pose a problem for reporting and access, as an Institute for Clinical and Economic Review The panel voted 10 to 2 that current evidence is sufficient to demonstrate a net health benefit compared to Abilify.
ICER ratings can support payers’ decisions regarding prescription drug coverage. Insurers or pharmacy benefit managers may require an outage on Abilify before reimbursing Cobenfy, a so-called fail-first policy.
That said, ICER’s analysis contains mixed results. A majority of ICER panelists (7-5) who reviewed the evidence found it sufficient to demonstrate a net health benefit compared to Zyprexa or Risperdal. And ICER placed a price range between $16,000 and $20,000 per year, which would align with the expected clinical benefit. This is relatively close to the list price of $22,500. With discounts and rebates, Cobenfy’s net price may fall within the acceptable price range suggested by ICER.
Still, the votes from ICER’s Technology Evaluation Panel leave some doubt regarding the cost-effectiveness of Cobenfy compared 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 ProgramManufacturers who want their medicines covered must pay back at least 23.1% of the average producer price to the government. In return, Medicaid must include the FDA-approved drugs made by those manufacturers.
However, plans that manage the pharmacy benefit can still set coverage limitations, including utilization management tools such as prior authorization, fail-first policy requirements, and duration of therapy limits. Accordingly, Cobenfy is unlikely to be a first-line treatment option for most patients. Instead, it is expected to be an option for patients who have a poor or partial response to atypical antipsychotics or for patients who cannot tolerate the side effects of weight gain, sedation, and movement disorders associated with atypical antipsychotics.
Competitive dynamics in the field of schizophrenia are likely to drive changes that present opportunities and challenges for Cobenfy’s sponsor, Bristol Myers Squibb. The company wants to increase the reach of the product during its research new indicationsincluding the use of Cobenfy as an adjunctive therapy for schizophrenia patients who do not respond adequately to their current atypical antipsychotic medications and testing for both bipolar disorder and the agitation often associated with Alzheimer’s disease. At the same time, Cobenfy could eventually be confronted competitionincluding the therapeutic emraclidine, a novel once-daily agent being studied in phase 2 for schizophrenia and psychosis in Alzheimer’s disease.