— Independent appraisal committee voted that current evidence is not adequate to demonstrate superior net health benefits for KarXT compared to generically available aripiprazole; if long-term data confirm KarXT’s benefits and lack of weight gain, it would achieve common thresholds for cost-effectiveness if priced between $16,000 to $20,000 per year — 

BOSTON, March 11, 2024 – The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report assessing the comparative clinical effectiveness and value of xanomeline tartrate/trospium chloride (Cobenfy or KarXT, Bristol Myers Squibb) for the treatment of schizophrenia.  

ICER’s report on these therapies was the subject of the February 2024 public meeting of the of the New England CEPAC, one of ICER’s three independent evidence appraisal committees. 

Downloads: Final Evidence Report | Report-at-a-Glance | Policy Recommendations 

“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.” 

ICER’s Virtual Public Meeting: Voting Results on Clinical Effectiveness and Contextual Considerations 

ICER assessed, and the independent appraisal committee voted on, the evidence of KarXT for adults with an established diagnosis of schizophrenia who are not considered to have treatment-resistant schizophrenia: 

  • A majority of panelists (10-2) found that current evidence is not adequate to demonstrate a net health benefit for KarXT when compared to aripiprazole. 
  • A slight majority of panelists (7-5) found that current evidence is adequate to demonstrate a net health benefit for KarXT when compared to olanzapine and/or risperidone. 

Panel members also weighed potential benefits and disadvantages beyond the direct health effects and broader contextual considerations. Voting highlighted the following as particularly important for payers and other policymakers to note: 

  • Acuity of need for treatment of individual patients based on short-term risk of death or progression to permanent disability; 
  • Magnitude of the lifetime impact on individual patients of schizophrenia. 

ICER’s Virtual Public Meeting: Voting Results on Long-Term Value for Money 

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), meaning a price range that matches the clinical benefit patients are expected to receive, for KarXT to be between $16,000 to $20,000 per year, however the lack of long-term data means that there is substantial uncertainty in this result.  

Consistent with ICER’s process, because there is no firm estimate yet of a potential launch price for the treatment, the panel did not take a vote on the treatment’s long-term value for money. 

Key Policy Recommendations: 

ICER’s independent assessment of value informs the critical decisions that stakeholders across the US health system need to make around pricing and coverage. Following the voting session, a policy roundtable of experts — including clinical experts, patient advocates, the manufacturer, and representatives from US payers — convened to discuss the pricing implications and recommendations to ensure fair access. Key recommendations stemming from the roundtable discussion include: 

  • All stakeholders have a responsibility and an important role to play in ensuring that effective new treatment options for people living with schizophrenia are introduced in a way that will help improve comprehensive care for people with schizophrenia and reduce health inequities, particularly for Black Americans. 
  • If KarXT receives FDA approval, payers should use the FDA label as the guide to coverage policy and engage clinical experts and diverse patient representatives in considering how to address coverage issues for which there is limited or no evidence at the current time.   
  • Manufacturers should set prices that will foster affordability and good access for all patients by aligning prices with the patient-centered therapeutic value of their treatments. In the setting of KarXT for people living with schizophrenia, while there is considerable hope associated with the promise of the drug, there also remains substantial uncertainty regarding its longer-term safety and effectiveness. Launch pricing should reflect these considerations. 

ICER’s detailed set of policy recommendations is available in the Final Evidence Report and in the standalone  Policy Recommendations document. 

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.