This e-alert is part of a series of e-alerts summarizing publicly available FDA enforcement letters (i.e., warning letters and untitled letters) relating to the advertising and promotion of prescription drugs, medical devices, and biologics.
During the first quarter of 2025 FDA’s Office of Prescription Drug Promotion (OPDP) posted the following two untiled letters.
- Untitled Letter to Edenbridge Pharmaceuticals, LLC d/b/a Dexcel Ltd. re NDA 211379 HEMADY (Dexamethasone tablets) for oral use (February 3, 2025) (Hemady Untitled Letter)
- Untitled Letter to Taiho Oncology, Inc. re NDA 214801 LYTGOBI® (futibatinib) tablets, for oral use (March 21, 2025) (Lytgobi Untitled Letter)
During the same period the Office of Product Evaluation and Quality (OPEQ) at the Center for Devices and Radiological Health (CDRH) posted the following two warning letters.
FDA’s Advertising and Promotional Labeling Branch (APLB) in the Office of Compliance and Biologics Quality (OCBQ) has not posted any enforcement letters since 2018.
This alert merely summarizes the allegations contained in FDA’s letters. It does not contain any analyses, opinions, characterizations, or conclusions by or of Covington & Burling LLP. As a result, the information presented herein does not necessarily reflect the views of Covington & Burling LLP or any of its clients.
Office of Prescription Drug Promotion (OPDP)
Untitled Letter to Dexcel Ltd. (February 3, 2025)
OPDP’s untitled letter to Edenbridge Pharmaceuticals, LLC d/b/a Dexcel Ltd. (Dexcel) alleges that an exhibit booth panel (exhibit panel) misbrands Hemady by making false or misleading representations about the risks and benefits of Hemady. Hemady is indicated in combination with other anti-myeloma products for the treatment of adults with multiple myeloma (MM).
False or Misleading Risk Presentation
OPDP alleges that the exhibit panel “is misleading because it presents efficacy claims for Hemady but fails to communicate any risk information.” Specifically, OPDP notes the exhibit panel includes the following claims:
- “HEMADY® reduces up to 80% of the number of tablets required for a therapeutic dose of dexamethasone for the treatment of adults with MM”
- “Hemady® is a unique strength dexamethasone tablet bioequivalent to five 4 mg tablets of dexamethasone”
OPDP alleges that by omitting the risks associated with Hemady while emphasizing the benefit, “the exhibit panel fails to provide material information about the consequences that may result from the use of Hemady and creates a misleading impression about the drug’s safety.”
False or Misleading Claims About Efficacy
OPDP also takes issue with a table on the exhibit panel titled “REAL-WORLD COMPARISON OF ADHERENCE to Hemady® and generic dexamethasone among patients with MM,” which OPDP alleges “suggest[s] improved patient adherence to Hemedy as compared with generic dexamethasone 4 mg tablets.” OPDP states that “[d]ata on file is cited to support the presentation” but claims that “the referenced study does not support conclusions regarding comparative adherence to Hemady and generic dexamethasone 4 mg in the treatment of patients with MM due to limitations associated with the study design and methodology.” OPDP points to a series of alleged limitations with the referenced study, including that “the patient selection methodology described in the study protocol was not consistent between patients treated with Hemady and generic dexamethasone 4 mg,” “the study protocol did not identify whether Hemady or generic dexamethasone 4 mg was used as monotherapy or as part of combination treatment regimens,” and “the study included a significantly higher number of patients in the generic dexamethasone 4 mg group (n=3,775) compared to the Hemady group (n=43), leataihding to a notably unbalanced sample size.”
Untitled Letter to Taiho Oncology, Inc. (March 21, 2025)
OPDP’s untitled letter to Taiho Oncology (Taiho) alleges that the “Efficacy Results” webpage on the Lytgobi Healthcare Provider Branded Website misbrands Lytgobi by making false or misleading representations about the benefits of the product. FDA notes that it previously addressed similar concerns about claims in advisory comments provided to Taiho in 2022. Lytgobi is indicated for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 gene fusions or other rearrangements. Lytgobi was approved under the accelerated approval pathway.
False or Misleading Benefit Presentation
OPDP alleges that the “Efficacy Results” webpage for Lytgobi includes a series of unsupported efficacy claims related to progression-free survival (PFS), overall survival (OS), and disease control rate (DCR). For example, the webpage includes:
- “A Presentation of a Kaplan-Meier estimate graph of PFS titled, ‘Progression-free survival (PFS),’ showing ‘Progression-free Survival (%)’ on the y-axis and ‘Months’ on the x-axis[.]”
- “Median [PFS], 9.0 mo (95% CI: 6.9, 13.1)”
- “Median follow-up at time of data cutoff was 17.1 months”
- “A Presentation of a Kaplan-Meier estimate graph of OS titled, ‘Overall survival (OS),’ showing ‘Overall Survival (%)’ on the y-axis and ‘Months’ on the x-axis[.]”
- “Median [OS], 21.7 mo (95% CI: 14.5, Not Reached)”
- “At the time of data cutoff: Median follow-up was 17.1 months; the OS data were not mature; during the study, 40 patients (39%) died following treatment discontinuation with the majority (90%) dying from disease progression.”
- The claim “83% DCR (95% CI: 74, 89)” depicted inside of a pie chart that includes shading to show the 83% DCR.
FDA alleges that these and other claims misbrand Lytgobi because the design of the study Taiho cites to support the claims, FOENIX-CCA2, is not capable of supporting the representations or suggestions. FDA alleges that because FOENIX-CCA2 was designed as a single-arm trial the results are 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.” Additionally, FDA states that “[a]n assessment of delay in time to disease progression in patients treated with Lytgobi [] would need to be based on the results of a randomized controlled trial.”
FDA acknowledges that Taiho’s website includes disclaimers, such as “Due to potential variability in the natural history of the disease, a single-arm study may not adequately characterize these time-to-event endpoints and the results may not be interpretable” and “The extended follow-up data were collected after the primary analysis and are descriptive in nature, and results should be interpreted with caution.” However, FDA finds that these disclaimers are inadequate. Specifically, FDA states that “[t]he disclosures of the study’s limitations (noted above) in this promotional communication do not correct or mitigate the misleading representations or suggestions of the presentation.”
CDRH Office of Product Evaluation and Quality (OPEQ) and ORA Office of Medical Device and Radiological Health Operations (OMDRHO)
Warning Letter to Next Science LLC (Issued February 2025, Posted March 2025)
FDA’s warning letter to Next Science LLC (Next Science), issued by OPEQ, arose out of an August 12 – September 5, 2024, inspection of the Next Science and review of the company’s website. FDA alleges that the inspection revealed that the Next Science is marketing wound gels (SURGX® and BLASTX®) and wound irrigation solutions (XPERIENCE® and Bactisure®) without 510(k) clearance, and consequently that these products are misbranded.
FDA alleges that:
- the XPERIENCE® product was cleared under K203835 as MIS Solution “indicated for use in cleansing and removal of debris, including microorganisms, from wounds”;
- the BLASTX® product was cleared under K150792 as Next ScienceTM Wound Gel for Over-The-Counter Use “indicated for the management of skin abrasions, lacerations, minor irritations, cuts, exit sites and intact skin”; and
- the SURGX® product was cleared under K163188 as Next Science nonsterile wound gel for Prescription Use and “indicated for the management of wounds such as Stage I-IV pressure ulcers, partial and full thickness wounds, diabetic foot and leg ulcers, post-surgical wounds, first- and second-degree burns, grafted and donor sites.”
However, FDA claims Next Science is marketing these products for additional uses outside of the scopes of clearance issued under K203835, K150792, and K163188, respectively, without obtaining clearance. FDA also states that “some of the claims raise jurisdictional issues, and if [the company] intend[s] to continue making such claims, the product may be regulated by the Center for Drug Evaluation and Research (CDER) and subject to drug requirements.”
Specifically, FDA took issue with a series of claims, including the examples listed below:
- XPERIENCE®
- “XPERIENCE rinses away debris and microorganisms from the surgical wound site.”
- “XPERIENCE does not have cytotoxic effects on osteoblasts. Cell viability and bone growth and healing were shown to be more favorable compared to 10% Betadine.”
- BLASTX®
- “BLASTX® has been shown to suppress inflammation and repair the skin’s barrier function.”
- “BLASTX® inactivates matrix Metalloproteases (MMPs), leading to stopping the cytokine cascade. Also, BLASTX® inactivates proteases production by the bacteria, which prevents tissue destruction and inflammation by the same mechanism.”
- SURGX®
- “SURGX® Sterile Antimicrobial Gel as sterilized by gamma radiation for one time use.”
- “SURGX® is designed to reduce surgical site and post-surgical infections by destroying planktonic and biofilm-encased bacteria within the gel. The proprietary, non-toxic formulation conforms to the postoperative wound to provide proven broad spectrum and sustained effectiveness for up to 5 days.”
FDA also alleges that Next Science is “marketing the XPERIENCE®, BLASTX® and SURGX® products as powered by XBIO® Technology and that the company makes claims that “XBIO® Technology deconstructs biofilm by removing the metal ions holding biofilm together.” For example, FDA highlights the following claims, among others:
- “Since 2012, Next Science has been developing revolutionary material science-based technology that is non-toxic with proven efficacy against bacteria and microorganisms. This technology is called XBIO®.”
- “XBIO™ Technology deconstructs biofilm by removing the metal ions holding it together.”
- “At Next Science, we are leading a paradigm shift with a unique approach to eradicating both biofilm bacteria and planktonic bacteria with our XBIO Technology. XBIO disrupts the biofilm’s extracellular polymeric substance and exposes the bacteria, once protected by the biofilm, leaving it more vulnerable to attack.”
Notwithstanding these claims, FDA alleges that the products “have not been evaluated for safety and effectiveness against biofilm.” FDA also states that it previously communicated these concerns to the company during a regulatory meeting held on May 5, 2022. FDA alleges that in 2022 it explained “the antimicrobial component[s] found in [the] 510(k) cleared products are intended to function as a preservative that inhibits growth of microorganisms in the products and claims of effectiveness against biofilm are outside the clearance of XPERIENCE®, BLASTX® and SURGX®.” FDA also alleges that the company’s claims “go beyond the types of claims appropriate for wound dressings and wound washes categorized under the FRO product code” and that the claims “raise jurisdictional issues” such that the products “may be regulated by CDER and subject to drug requirements.”
Warning Letter to Red Oak Instruments, LLC (Issued February 2025, Posted April 2025)
FDA’s warning letter to Red Oak Instruments, LLC (Red Oak), issued by OPEQ, arose out of a July 15 – 26, 2024, inspection of the company and review of Red Oak’s website. FDA alleges that the inspection revealed that Red Oak is marketing an AC Powered Dynamometer RU-Fit (Model SR-3053) medical device with major changes or modifications to the intended use without submitting a new 510(k) premarket notification to FDA.
According to FDA, AC-powered dynamometer devices classified under 21 CFR 888.1240 are exempt from premarket notification. Such devices are intended “to assess neuromuscular function or degree of neuromuscular blockage by measuring, with a force transducer (a device that translates force into electrical impulses), the grip-strength of a patient's hand.” However, FDA alleges “there is evidence that the RU-FIT (Model SR-3053) is intended for uses that are different from those of legally marketed devices classified under 21 CFR 888.1240 AC-powered dynamometer.” Specifically, FDA alleges “the device is intended to screen for possible mild traumatic brain injury (mTBI), also known as concussion.” FDA points to the following claims, among others, as evidence of this point:
- “This device is intended to screen for possible head injuries in the cases of head impact where there is not any visible blood, other than minor scraps [sic].”
- “The SR-3053 should be used…to compare recognition and choice reaction times of an injured or non-injured individual.”
- “Summary Sheet For Concussive Impact”
- “Since denial is a strong symptom of mTBI subjects, the necessary compliance is not always achievable. A better technology is needed. RedOak Instruments provides the needed technology.”
- “RedOak Instruments, LLC is a USA based biomechanical and software-based company which provides objective physiological measurements to screen for injuries, ailments and to monitor recovery. The test will document the reduction or improvement of factors related to head injury including fine motor control, coordination and reaction time.”
FDA also claims that because the RU-FIT (Model SR-3053) was previously cleared under K012492 for specific indications, which do not include mTBI, promoting the device to screen for possible mTBI “would constitute a major change or modification to its intended use, for which [Red Oak] lacks clearance or approval.”
If you have any questions concerning the material discussed in this client alert, please contact the members of our Food, Drugs, and Devices practice.
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