Just in time for the holidays, on December 15, 2025, the U.S. Food and Drug Administration (“FDA”) Office of Prescription Drug Promotion (“OPDP”) issued an untitled letter (the “Letter”) to Karuna Therapeutics, Inc., a Bristol Myers Squibb Company, concerning a direct-to-consumer broadcast ad for Cobenfy™ (xanomeline and trospium chloride), a drug approved for the treatment of schizophrenia.[1] As we have previously covered at length,[2] the administration continues to crack down on direct-to-consumer (“DTC”) advertising. Notably, this Letter is the second untitled letter released since the government shutdown, demonstrating that DTC advertising remains a key priority.
The Letter touches on familiar enforcement themes, such as ad presentation and form and promotion consistent with FDA-required labeling (“CFL”), while zeroing in on industry pitfalls—from the traditional “overstatement” of benefits and “implied” efficacy in unstudied populations to distracting visuals—offering a good example of what FDA will and will not tolerate in the current regulatory landscape.
Promotional Content
The Letter focuses on a TV advertisement for Cobenfy™, a novel combination product for schizophrenia. The ad depicts a patient surrounded by schizophrenia symptoms—“delusions,” “disorganized thoughts,” “voices,” “lack of emotion,” “low motivation,” and “less social interaction”—followed by the assertion that “Cobenfy showed overall improvement across a range of schizophrenia symptoms,” paired with on-screen visuals linking “positive” and “negative” symptoms.
Issues Noted in the Letter
FDA’s first objection was that this layout and messaging misrepresents the evidence. According to FDA, there is no basis to say Cobenfy™ improves negative symptoms as a distinct group, because the pivotal trials were designed to evaluate overall symptom severity (as measured by the combined Positive and Negative Syndrome Scale (“PANSS”) total score), not specific domain changes in positive versus negative symptoms. The studies also enrolled patients in acute episodes, which FDA believed could cloud assessment of the product’s impact on negative symptoms. FDA notes that qualifiers in the ad’s Super (“in two 5-week clinical studies, a rating scale measured changes in schizophrenia symptoms overall…”) don’t sufficiently correct the misleading impression. As FDA has emphasized many times before, disclaimers cannot cure an allegedly misleading claim when the agency does not agree with the underlying data used to support it.
The Letter also takes issue with a voiceover urging viewers: “If you still have symptoms, be bold and ask your healthcare provider about Cobenfy.” FDA appears to hang its hat on the use of the word “still,” interpreting it as misleadingly implying that Cobenfy™ is effective in treatment-resistant schizophrenia—a population in which the product has not been studied. The pivotal trials were placebo-controlled with no active comparator, and FDA noted a lack of evidence that it works when other antipsychotics have failed.
FDA also challenged the classification of the drug (i.e., claims that “Cobenfy is not an antipsychotic”). The ad Super clarifies the product’s mechanism as a muscarinic agonist/antagonist combination, but FDA points out that what matters for classification is indication and therapeutic effect—not just mechanism. In other words, if it treats psychosis, it’s an antipsychotic.
Like we have seen with other letters, particularly in the slew of untitled letters issued back in September, the critique is not just about words—visuals that dazzle consumers do not get a pass if they distract from the critical risk information FDA expects to be clearly conveyed.[3] Here, FDA calls out the “compelling, attention-grabbing visuals”—skateboarding, petting a dog, DJ booth montages—as interfering with comprehension of the major statement of risks.
Key Takeaways
Be Careful with Claims about Symptom Groups and Rating Scales
Based on prior enforcement actions, as well as what FDA has said publicly, we know that FDA closely reviews product promotion—sometimes with the help of AI tools—and FDA-approved prescribing information (“PI”) to ensure that all claims are properly substantiated. Although a drug may show some benefit on an overall or composite basis, for certain therapeutic areas, FDA wants claims about benefits for specific subgroups assessed within a rating scale—such as negative symptoms in schizophrenia—to be substantiated by evidence (at least at a level FDA deems sufficient) or otherwise assessed prospectively within the context of the clinical trial design.
This appears to be a classic case of FDA simply disagreeing with the manufacturer and insisting that, to support claims of negative symptom relief, the manufacturer must either cite studies specifically demonstrating such benefits or conduct a trial designed to show improvement in negative symptoms.
Broader Efficacy Claims are a No-Go
Another issue raised by FDA is that promotional messaging must not imply the product is effective in populations or circumstances not supported by sufficient data, like here where FDA flagged an implied claim that the product is effective in treatment-resistant patients. It is notable that the manufacturer used the word “still,” though the Letter provides little context or rationale behind the choice. FDA seems focused on this phrasing, emphasizing that no data was provided comparing Cobenfy™ with other antipsychotics. While the intent may have been to address patients who continue to experience symptoms irrespective of prior treatment, FDA interpreted the wording as suggesting that other therapies had already failed—a position not supported by the available data. This serves as a clear reminder that FDA will closely scrutinize even seemingly minor word choices—such as “still”—if they create any suggestion of use that is not CFL.
Class Labels Matter
The FDA’s position, as reflected in the Letter, is that drug classification is determined by therapeutic indication and clinical use, not solely by mechanism of action. In the case of Cobenfy™, despite its novel mechanism, the product is approved for the treatment of schizophrenia, a form of psychosis. Therefore, FDA considers Cobenfy™ to be part of the antipsychotic drug class, which FDA defines generally as “drugs used to treat symptoms of severe psychiatric disorders.”
Conclusion
The Letter highlights familiar themes in FDA’s ongoing scrutiny of direct-to-consumer advertising and sets fresh reminders for the industry. Key enforcement targets remain: ensuring claims are tied directly to trial data, avoiding overstated or implied benefits outside studied populations, and being mindful of both substance and presentation. As DTC advertising continues as an enforcement priority post-shutdown, companies should carefully review all claims, visuals, and messaging.
FOOTNOTES
[1] Untitled Letter available here: COBENFY | Untitled Letter | 12.15.2025
[2] FDA’s Wave of Untitled Letters Signals Stricter Scrutiny for DTC Pharma Ads | FDA Law Update
[3] FDA’s Wave of Untitled Letters Signals Stricter Scrutiny for DTC Pharma Ads | FDA Law Update