Déjà Vu: OPDP Again Targets Provider Branded Website of Accelerated Approval Drug in Second Untitled Letter of 2025

FDA’s Office of Prescription Drug Promotion (OPDP) issued its second Untitled Letter of 2025 to Taiho Oncology (Taiho) for a healthcare provider branded website for its drug LYTGOBI (futibatinib). This letter, dated March 21, 2025, cites Taiho’s false or misleading representations about the benefits of the drug, which is considered misbranding under the Federal Food, Drug, and Cosmetic Act. The letter is notable as it is the second OPDP enforcement letter describing violative promotion about an accelerated approval drug within the last six months. Join us as we break down what went wrong this time.

What Happened?

LYTGOBI was granted accelerated approval for the treatment of adult patients with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma (iCCA) with FGFR2 gene fusions or rearrangements. The FDA’s accelerated approval pathway can allow for earlier approval of drugs intended to treat serious conditions and fill an unmet medical need where approval is based on an effect on a surrogate or intermediate clinical endpoint that is reasonably likely to predict clinical benefit and the predicted clinical benefit is subsequently verified in a post-approval confirmatory trial(s). The Untitled Letter notes that the confirmatory trial for LYTGOBI is currently ongoing and has not been completed; therefore, clinical benefit of LYTGOBI has not yet been confirmed.

OPDP’s concerns center on Taiho’s “Efficacy Results” webpage, which highlights Kaplan-Meier survival curves for progression-free survival (PFS) and overall survival (OS), along with data from additional endpoints, from Taiho’s Phase 2 study, FOENIX-CCA2. The problem? As a single-arm trial (i.e., no comparator arm), FOENIX-CCA2 was not capable of establishing improvement on time-to-event efficacy endpoints such as PFS or OS and, without an appropriate comparator, “it is not possible to determine if the observed effect is attributable to LYTGOBI or to other factor(s), such as the natural history of the disease.” The website also reports a disease control rate (DCR) of 83% based on a non-prespecified follow-up analysis conducted 8 months after the primary analysis. DCR is defined as “the sum of complete response (CR), partial response (PR) and stable disease (SD).” However, the Untitled Letter describes the single-arm FOENIX-CCA2 trial could not establish that the observed SD was attributable to the effect of the drug so the webpage misleadingly suggests that LYTGOBI improves DCR in patients with locally advanced or metastatic iCCA based on a composite of CR, PR, and SD. The Untitled Letter states that a randomized controlled trial would be needed to assess delay in time to disease progression.

Taiho’s website also featured (less prominently) a number of disclaimers such as, “This data presentation is neither intended to draw conclusions regarding the efficacy of LYTGOBI nor to imply that there is a treatment effect of LYTGOBI on these time-to-event endpoints and the results should be interpreted with caution,” and “The extended follow-up data were collected after the primary analysis and are descriptive in nature, and results should be interpreted with caution.”

Not surprisingly, these disclaimers were simply not enough. The FDA emphasizes that intrahepatic bile duct cancers have an estimated 5-year relative survival rate and unresectable, locally advanced or metastatic iCCAs, such as those for which LYTGOBI is conditionally approved, is a serious public health concern where surgery is not an option and treatment for the condition involves serious risks. In such serious cancers, survival data is one of the most critical factors influencing treatment decisions and disclosures of the FOENIX-CCA2 trial’s limitations on the webpage do not correct or mitigate the misleading representations or suggestions of LYTGOBI’s efficacy.

Echoes from Past Warnings

The disclaimers included on the website were likely derived from FDA commentary on previously submitted marketing pieces. According to the Untitled Letter, the FDA previously pointed out concerns about Taiho’s marketing messages, particularly regarding the selective presentation of efficacy data. With this latest Untitled Letter, the Agency is sending another strong signal that failure to correct misleading claims could lead to harsher consequences.

But, where have we heard this all before? The Taiho Letter has almost identical observations to those cited in the 2024 Untitled Letter to Mirati Therapeutics Inc. (Mirati) about a healthcare professional branded website for KRAZATI (adagrasib). Promotion for KRAZATI, which was granted accelerated approval for patients with certain types of non-small cell lung cancer, was objectionable because of claims about DCR, OS and PFS based on a single-arm study. In that case, as in this instance, the inclusion of disclaimers did not mitigate the misleading impression left by the claims.

Both cases involve oncology drugs granted accelerated approval. Accelerated approval requires companies to submit all promotional materials for their product thirty (30) days in advance of the material being used. FDA did not object to the timing of the respective submissions in either letter.

Promoting Accelerated Approval Drugs

Taiho now faces a choice: revise its marketing approach or risk further regulatory action from the FDA.

Separately, these bloggers wonder whether the Untitled Letter to Taiho signals a specific focus on accelerated approval product promotion. Unlike the Untitled Letter to Mirati, the Taiho Letter includes no reference to FDA’s Bad Ad program – indicating that Taiho’s materials were on OPDP’s radar for other reasons. This newest letter makes 1/3 of the letters issued by OPDP over the past 12 months directed toward promotion of accelerated approval drugs. (Lest we be accused of overstating, in absolute numbers this means two out of the six Untitled Letters OPDP has issued.)

Marketing an accelerated approval drug can be messy. Marketers are often put in the difficult position of submitting materials 30 days in advance of use and then having to decide whether to “go live” with those materials when comments have not been received from FDA within that time frame. As readers of enforcement letters, we have the benefit of 20/20 hindsight when looking at promotional material, seeing study limitations disclosures and knowing they were insufficient to contextualize the representations. However, companies oftentimes need to make risk/benefit decisions about how to proceed with messaging and including disclosures/disclaimers is critical to ensuring presentations can be defended as truthful and non-misleading.

While it is our understanding OPDP staff responsible for reviewing advertising and promotional materials were not subject to the April 1 reduction-in-force, other areas of OPDP were impacted, which may lead to longer promotional material review timelines. Given these recent changes, these bloggers wonder whether the Taiho Letter may be the last Untitled Letter we see for some time, as the remaining FDA staff continue to navigate these unprecedented times. While we don’t always see eye-to-eye with OPDP reviewers when determining whether a communication is false or misleading, we’ve always appreciated that their perspective is grounded in FDA’s mission to protect the public health.