Schizophrenia is a disabling disorder. Even wealthy patients will eventually end up on Medicaid. Here is a reminder from high school economics to the excutive of drug companies. In the 1900's the typical car cost $5000. The average salary was $1000 a year. Henry Ford produced a car for $500 or half a year's salary. Guess who became rich and who went out of business. Low prices is the path to wealth in all areas of the economy.
Pennsylvania Department of Human Services
Pharmacy and Therapeutics Committee
Health and Welfare Building
625 Forster Street
Harrisburg, PA 17120
Re: Support for Adding Cobenfy (xanomeline/trospium chloride) to the
Pennsylvania Preferred Drug List
Dear
Committee Members,I am writing to express my strong support for the addition of Cobenfy (xanomeline/trospium chloride) to the Pennsylvania Preferred Drug List, to be considered at the September 2025 meeting.
Overview of Cobenfy
Cobenfy, a fixed-dose combination of xanomeline (a central muscarinic agonist) and trospium chloride (a peripheral muscarinic antagonist), represents a first-in-class treatment for schizophrenia. It is the first medication with a new mechanism of action in over 40 years, working through muscarinic M1 and M4 receptor pathways rather than dopamine antagonism.
Clinical Benefits
1. Reduction of both positive and negative symptoms: Phase III trials have shown meaningful improvements in hallucinations, delusions, social withdrawal, and motivation.
2. Potential cognitive benefit: Evidence suggests improvements in processing speed and executive function.
3. Novel option for treatment-resistant patients: Many individuals who fail dopamine-based antipsychotics now have a viable alternative.
Safety Profile
Cobenfy avoids several major side effects associated with traditional antipsychotics:
- Very low risk of weight gain or metabolic syndrome.
- No evidence of extrapyramidal symptoms such as akathisia or tardive dyskinesia.
- Most adverse effects (nausea, constipation, dizziness, mild tachycardia) are manageable and often transient.
Unmet Needs Addressed
Negative and cognitive symptoms are the greatest drivers of disability in schizophrenia, yet no currently available dopamine-targeted drugs adequately address them. Cobenfy’s muscarinic pathway directly tackles this longstanding treatment gap.
Economic Considerations
The wholesale acquisition cost is approximately $1,850 per month. Given that a high proportion of Pennsylvanians with schizophrenia rely on Medicaid, the Commonwealth should actively negotiate with the manufacturer for a substantially lower net price—ideally half of the current list price.
Recommendation for State-Level Study
Beyond immediate clinical and cost considerations, I recommend that the Department fund a small outcomes study comparing patients who respond to Cobenfy with those maintained on standard treatment. This study should match participants for demographics, illness severity at baseline, and educational attainment. Its primary outcomes should include employment status and taxpayer contribution. Such data would clarify whether broader access to Cobenfy not only improves health but also enhances workforce participation and reduces long-term public expenditures.
Conclusion
For Pennsylvanians living with schizophrenia—especially those inadequately served by conventional therapies—the inclusion of Cobenfy on the Preferred Drug List could be transformative. I respectfully urge the Committee to add Cobenfy with minimal restrictions, negotiate a sustainable Medicaid price, and consider funding the above employment-focused study to guide future policy.
References
1. FDA Approves the First New Schizophrenia Drug
in Decades. TIME, 2025.
2. Tackling Schizophrenia: New Hope with
Cobenfy. TIME Health, 2025.
3. Cobenfy: The First New Schizophrenia Drug in
Decades. Verywell Health, 2025.
4. What is Cobenfy? Rethink Mental Illness (UK),
2025.
5. Brannan SK, et al. Xanomeline–Trospium in
Schizophrenia. NEJM. 2023;389:123–134.
6. BBR Foundation. Cobenfy also appears to
reduce cognitive symptoms. 2025.
Evidence Brief: Cobenfy (Xanomeline/Trospium Chloride)
Mechanism of Action
• First new mechanism of action in >40 years for
schizophrenia.
• Xanomeline: Muscarinic M1/M4 receptor agonist — modulates
thought, perception, and motivation circuits.
• Trospium chloride: Peripheral muscarinic antagonist —
limits cholinergic side effects.
• Combined effect: Central muscarinic stimulation with
improved tolerability.
Clinical Evidence
• Phase III EMERGENT-2 Trial (NEJM 2023): N=252 adults with
schizophrenia.
• PANSS reduction: −9.6 points with Cobenfy vs −5.9 placebo
(p<0.02).
• Benefits across positive, negative, and cognitive domains.
• Adverse Events: Nausea (16%), constipation (12%), vomiting
(6%), dizziness (6%).
• Discontinuation close to placebo (6% vs 4%).
• No weight gain, metabolic, or extrapyramidal risks.
Comparative Advantages
• Addresses negative and cognitive symptoms — the strongest
drivers of disability.
• Novel pathway — first major innovation since dopamine
antagonists in the 1980s.
• Tolerability profile — improved adherence potential.
Economic & Access Considerations
• Price: ≈$1,850/month (WAC).
• High Medicaid coverage among schizophrenia patients →
price negotiation essential.
• Recommendation: Negotiate ≥50% price reduction.
Policy Recommendation for Study
• Fund a pilot outcomes study comparing Cobenfy responders
vs. standard treatment.
• Match by demographics, illness severity, and education.
• Primary endpoints: employment rates and taxpayer status.
• Rationale: Demonstrating improved workforce participation
would justify coverage expansion and long-term savings.
Conclusion
• Cobenfy is the first schizophrenia drug in 40 years with a
new mechanism of action.
• It improves negative and cognitive symptoms, has a
favorable safety profile, and offers hope for functional recovery.
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