KarXT has a novel mechanism of action, but there are significant uncertainties regarding long term efficacy and safety; KarXT would achieve common thresholds for cost-effectiveness if priced between $16,000 to $20,000 per year —

BOSTON, January 25, 2024 – The Institute for Clinical and Economic Review (ICER) today posted its revised Evidence Report assessing the comparative clinical effectiveness and value of xanomeline tartrate/trospium chloride (KarXT, Karuna Therapeutics) for the treatment of schizophrenia. 

“Schizophrenia is a serious mental illness that affects how a person thinks, feels, and behaves,” said ICER’s Chief Medical Officer, David Rind, MD. “Among the important side effects of current treatments is weight gain leading to metabolic syndrome. This, in turn, places patients at risk for cardiovascular events and death. KarXT has a novel mechanism of action and, at least in the short run, does not seem to cause weight gain. This may lead to major health benefits compared with existing treatments, however current evidence on benefits and harms is limited.”

This Evidence Report will be reviewed at a virtual public meeting of the New England CEPAC (New England CEPAC) on February 9, 2024. The New England CEPAC is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy.

A draft version of this report was previously open for a four-week public comment period. The updated Evidence Report and voting questions reflect changes made based on comments received from individuals living with schizophrenia and patient groups, clinicians, drug manufacturers, and other stakeholders. Detailed responses to public comments can be found here.

Key Clinical Findings

KarXT was associated with significantly lower weight gain, which may translate into fewer cases of metabolic syndrome, diabetes, and cardiovascular complications over the longer term. However, the only available data on the efficacy and side effect profile of KarXT are for five weeks of in-hospital treatment of patients having an acute exacerbation of schizophrenia. Given the lack of long-term data, ICER rated the net health benefit of KarXT as promising, but inconclusive (P/I).

Key Cost-Effectiveness Findings

KarXT has not yet been approved by the FDA, and the manufacturer has not announced a US price if approved. ICER has calculated a health-benefit price benchmark (HBPB) for KarXT to be between $16,000 to $20,000 per year.

ICER’s HBPB is a price range suggesting the highest US price a manufacturer should charge for a treatment, net of all rebates and discounts, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.

About ICER

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.