October 29, 2024, Covington Alert

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 third quarter of 2024 FDA’s Office of Prescription Drug Promotion (OPDP) posted the following three untiled letters.

  • Untitled Letter to AbbVie, Inc. re NDA 211765 UBRELVY (ubrogepant) tablets, for oral use (August 29, 2024) (Ubrelvy Untitled Letter)
  • Untitled Letter to Mirati Therapeutics Inc. (a Bristol Myers Squibb Co.) re NDA 216340 KRAZATI™ (adagrasib) tablets, for oral use MA 166 (August 1, 2024) (Krazati Untitled Letter)
  • Untitled Letter to Kaleo, Inc. re NDA 201739 AUVI-Q® (epinephrine injection, USP), for intramuscular or subcutaneous use MA 1021 (July 17, 2024) (Auvi-Q Untitled Letter)

The Office of Product Evaluation and Quality (OPEQ) at the Center for Devices and Radiological Health (CDRH) and the Office of Medical Device and Radiological Health Operations (OMDRHO) in the Office of Regulatory Affairs (ORA) did not post any warning letters relating to the advertising and promotion of medical devices during this period. 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 AbbVie, Inc. (August 29, 2024)

OPDP’s untitled letter to AbbVie, Inc. (AbbVie) alleges that a TV ad misbrands Ubrelvy by making false or misleading representations and suggestions about the efficacy of Ubrelvy. Ubrelvy is indicated for the acute treatment of migraine with or without aura in adults. Although portions of the letter are redacted, OPDP notes that it previously provided advisory comments on claims and presentations similar to those in the TV ad.

False or Misleading Benefit Presentation

OPDP alleges that the TV ad, which features Serena Williams, “misleadingly suggests that Ubrelvy will provide a greater treatment benefit to patients suffering from migraine headache than has been demonstrated.”

First, OPDP alleges that the advertisement “misleadingly suggests that Ubrelvy eliminates migraine pain and symptoms more quickly than was demonstrated in the clinical trials.” OPDP states that “[a]ccording to the CLINICAL STUDIES section of the Ubrelvy PI, the efficacy of Ubrelvy for the acute treatment of migraine was established in two clinical trials based on two endpoints: 1) effect on pain freedom at two hours post-dose (defined as a reduction of moderate or severe headache pain to no pain) and 2) effect on most bothersome symptom (MBS) (i.e., photophobia, phonophobia, nausea) freedom at two hours post-dose (defined as the absence of the self-identified MBS), compared to placebo.” OPDP explains that the claim “[s]ome people had pain freedom within 2 hours” appears in the ad but alleges that this is “not sufficient to mitigate this misleading suggestion that Ubrelvy can eliminate migraine pain and symptoms more quickly than has been demonstrated.”

Second, OPDP takes issue with the claim that “[o]ne dose works fast to eliminate migraine pain” (emphasis added by OPDP), stating that it “misleadingly suggests that all patients who take Ubrelvy can expect their migraine pain to be eliminated after a single dose of Ubrelvy, when this has not been demonstrated.” Again, OPDP noted that the disclaimer that “[s]ome people had pain freedom within 2 hours” appears in the frame but OPDP contends that it is not sufficient to “mitigate the misleading suggestion that ‘one dose eliminate[s] migraine pain.’”

Untitled Letter to Mirati Therapeutics Inc. (a Bristol Myers Squibb Co.) (August 1, 2024)

OPDP’s untitled letter to Mirati Therapeutics Inc. (Mirati) alleges that a webpage on the Healthcare Provider Branded Website for Krazati makes false or misleading claims and representations about the efficacy of Krazati. Krazati is indicated “for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy.” Krazati was approved under the accelerated approval pathway based on the results from a multicenter, single-arm, open-label expansion cohort study that evaluated the effect of Krazati on two efficacy endpoints: Objective Response Rate (ORR) and Duration of Response (DOR) (KRYSTAL-1).

False or Misleading Benefit Presentation

First, OPDP alleges that Mirati misleadingly suggests that Krazati improves the Disease Control Rate (DCR) and “depth of response” in patients based on a composite of complete response (CR), partial response (PR), and stable disease (SD) data, “even though the study was not designed to demonstrate this.” Specifically, OPDP states that “because KRYSTAL-1 was designed as a single arm trial, the study did not establish that the SD result was attributable to the effect of the drug.” Moreover, “the DCR calculations, which are based on a composite that includes SD data, and the associated ‘depth of response’ claim, are not supported by the data cited.”

Second, OPDP alleges that Mirati makes misleading claims regarding the overall survival (OS) and PFS (progression free survival) rates. Specifically, OPDP takes issue with the claims “‘MEDIAN OS IN PATIENTS TAKING KRAZATI: 14.1 MONTHS,’ and ‘MEDIAN PFS IN PATIENTS TAKING KRAZATI: 6.9 MONTHS’ in conjunction with two graphs presenting ‘Survival Probability’ and ‘PFS Probability,’ over time (months), respectively.” According to OPDP, the data from KRYSTAL-1 cannot support these claims because these are “time-to-event efficacy endpoints” and “[t]ime-to-event efficacy endpoints in a single-arm trials are generally uninterpretable because it is not possible to determine if the observed effect (e.g., survival time) is attributable to the drug or the natural history of the disease.” Therefore, OPDP states that “it is misleading to make such representations or suggestions about the efficacy of this drug based on KRYSTAL-1, which, as a single-arm trial, is not capable of supporting such representations or suggestions.” OPDP acknowledges that the text “‘descriptive analysis’ appears under the ‘OS’ and ‘PFS’ navigation bar item headers when you click to view each of the items” and that the page displays include a disclosure of the study limitations, stating “single-arm trials do not adequately characterize time-to-event endpoints such as OS/PFS. Thus, these data from KRYSTAL-1 cannot be interpreted as having OS/PFS benefit.” However, OPDP concludes that the allegedly misleading statement “is not corrected by disclosure of the study’s limitations.”

Third, OPDP alleges that a graph titled “DESCRIPTIVE ANALYSIS MEDIAN DOR IN PATIENTS TAKING KRAZATI: 12.5 MONTHS” overstates the efficacy of Krazati by stating that the median DOR is 12.5 months when, according to OPDP, the “median DOR for patients treated with Krazati is 8.5 months with a 95% confidence interval of 6.2 months to 13.8 months.” OPDP states that “FDA is not able to verify the presented results, and FDA is not aware of data that support your claim that the median DOR for patients treated with Krazati is 12.5 months.”

Fourth, OPDP alleges that claims that “33% INTRACRANIAL ORR IN PATIENTS WITH STABLE, ADEQUATELY TREATED BRAIN METASTASES” and “INTRACRANIAL DCR IN PATIENTS WITH BRAIN METASTASES: 85% (n=33; 95% CI: 68-95)” are misleading because they “imply that Krazati is effective in treating brain metastases even though such an effect is not established by [the cited] post hoc analysis.” OPDP states that the text “POST HOC ANALYSIS” and the disclosure “INTRACRANIAL ORR AND DCR CANNOT BE ATTRIBUTED TO KRAZATI ALONE GIVEN BRAIN METASTASES WERE PREVIOUSLY TREATED, SOME WITH RECENT PRIOR RADIATION. THESE RESULTS SHOULD BE INTERPRETED WITH CAUTION” are not sufficient “to mitigate the overall misleading impression created by the inclusion of this presentation.”

Untitled Letter to Kaleo, Inc. (July 17, 2024)

OPDP’s untitled letter to Kaleo, Inc. (Kaleo) alleges that a social media post for Auvi-Q is false or misleading in that it presents information about the benefits of Auvi-Q but fails to include any risk information about the drug. Auvi-Q is “indicated in the emergency treatment of allergic reactions (Type I) including anaphylaxis to stinging insects . . . and biting insects . . . allergen immunotherapy, foods, drugs, diagnostic testing substances . . . and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis.” The social media post was made by Brittany Mahomes on her personal Instagram account in “[p]aid partnership with auvi-q.”

False or Misleading Risk Presentation

OPDP alleges that the social media post is false or misleading in that it presents information about the benefits of Auvi-Q but fails to include any risk information about the drug. OPDP takes issue with the following claims:

  • “So, I have an infant and a toddler both who have severe food allergies . . . . Based on my experience, I can tell you that a severe reaction may not look how you think it should look. So, after the diagnosis, a big part of the plan was going to my pediatrician, and he did prescribe me Auvi-Q. Auvi-Q is the only epinephrine autoinjector out there for infants and toddlers.”
  • “AUVI-q® (epinephrine injection, USP) is for life-threatening allergic emergencies.”
  • “[S]haring my experience with [my child’s] severe allergic reaction to peanuts . . . . partnering with @auvi_q to help spread awareness about severe food allergies in young children and how to best respond . . . . AUVI-q 0.1 mg is for infants and toddlers 16.5-33 lbs.”

OPDP acknowledges that the post includes the statement, “[f]or Important Safety Information, visit @auviq_ISI[.]” However, OPDP states that “this does not mitigate the misleading impression created by the omission of risk information” and that “[b]y omitting the risks associated with Auvi-Q, the post fails to provide material information about the consequences that may result from the use of Auvi-Q and creates a misleading impression about the drug’s safety.”

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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Photo of Scott Cunningham Scott Cunningham

Scott Cunningham is a member of the firm’s Food and Drug practice group.  He represents pharmaceutical, biotechnology, and medical device companies as well as trade associations in matters before the FDA, Congress, state and federal courts, and other regulatory and enforcement agencies.  Scott has…

Scott Cunningham is a member of the firm’s Food and Drug practice group.  He represents pharmaceutical, biotechnology, and medical device companies as well as trade associations in matters before the FDA, Congress, state and federal courts, and other regulatory and enforcement agencies.  Scott has significant experience in areas including new product development and clinical trials; IRBs; new product approvals; Hatch-Waxman exclusivities and product life-cycle management; advertising and promotion; False Claims Act and Anti-Kickback compliance issues and pharmaceutical investigations; Orphan Drug; pediatric exclusivity; manufacturing and cGMPs; import/export; controlled substances; SEC disclosure; and other aspects of federal and state regulation of pharmaceuticals, biologics, and medical devices.

Scott also has an active pro bono practice where he regularly serves as a Guardian ad Litem representing children in neglect & abuse and child custody cases.

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Scott Danzis is a partner in Covington’s Food, Drug, and Device Practice Group and chairs the Firm’s Medical Device Industry Group. Scott is a leading expert on the regulation of medical devices, diagnostics, and digital health. He regularly helps clients navigate their most…

Scott Danzis is a partner in Covington’s Food, Drug, and Device Practice Group and chairs the Firm’s Medical Device Industry Group. Scott is a leading expert on the regulation of medical devices, diagnostics, and digital health. He regularly helps clients navigate their most complex regulatory challenges, including strategies for premarket review, postmarket compliance, and enforcement actions. Scott counsels many of the world’s preeminent medical device companies on a range of matters, including advertising and promotion, recalls, quality system issues, medical device reporting, clinical and non-clinical testing, FDA inspections, and other regulatory matters.

Scott previously served in FDA’s Office of the Chief Counsel where he served as the Special Assistant to the Chief Counsel of FDA. At FDA, Scott was involved in a wide range of legal and regulatory matters, including significant rulemaking, enforcement actions, and legislative initiatives.

Scott speaks regularly at conferences regarding FDA regulation of devices and diagnostics, and since 2010 serves as an Adjunct Professor of Law at the Georgetown University Law Center, where he teaches a course on FDA law.

Scott is a graduate of the University of Virginia School of Law where he was the Editor-in-Chief of the Virginia Law Review and elected to the Order of Coif. He also holds a Master’s Degree from George Washington University and a Bachelor of Science from Cornell University.

From 2006 to 2008, Scott served as the Special Assistant to the Chief Counsel of the U.S. Food and Drug Administration. While at FDA, he was broadly involved in a wide range of legal and regulatory matters related to medical devices and drugs. He also worked on implementing key provisions of the Food and Drug Administration Amendments Act of 2007.

Scott has significant experience in the following areas:

  • FDA regulatory strategies, including strategies for the premarket review (510(k)s, PMAs) of medical devices;
  • Appeals and dispute resolution within FDA;
  • IDEs, INDs, and clinical trial regulation;
  • Advertising, promotion, and scientific exchange, including responding to enforcement actions and investigations;
  • Imports and exports of FDA regulated products;
  • QSR and cGMP requirements, including responding to FDA 483s and enforcement actions;
  • Product recalls;
  • Adverse event and MDR reporting;
  • FDA consent decrees and OIG corporate integrity agreements;
  • Regulatory due diligence;
  • Compliance with antifraud statutes, including the anti-kickback statute and the False Claims Act.

Scott recently developed and edited a book on the regulation of in vitro diagnostic products and laboratory testing, In Vitro Diagnostics: The Complete Regulatory Guide (FDLI, 2010). He currently serves as an Adjunct Professor at the Georgetown University Law Center where he teaches a course on the regulation of drugs, biologics, and medical devices.

Scott clerked for the Honorable Chester J. Straub on the U.S. Court of Appeals for the Second Circuit. He is a graduate of the University of Virginia School of Law where he was the Editor-in-Chief of the Virginia Law Review and elected to the Order of the Coif. He holds a Masters Degree from George Washington University in Health Care Management and Policy, and a Bachelor of Science from Cornell University.

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Christina Kuhn advises medical device, pharmaceutical, and biotech companies on a broad range of FDA regulatory strategy and compliance matters. She has experience with cutting-edge and complex medical technologies, including software and digital health products, oncology products, next-generation sequencing, diagnostics, and combination products.

Christina frequently helps multinational device manufacturers as well as start-up device companies navigate the premarket regulatory process, advising companies on regulatory classification, clinical development strategy, and agency interactions. She also has significant experience counseling medical device companies on postmarket compliance requirements, including those related to advertising and promotion, quality systems and manufacturing, medical device reporting, registration and listing, and recalls. She advises clients on responding to and resolving enforcement actions, such as FDA inspections and Warning Letters as well as Department of Justice investigations.

Christina advises clients on, and performs regulatory due diligence for, corporate transactions, including acquisitions, public offerings, co-development agreements, and clinical trial agreements.

Christina also regularly assists industry associations and medical device and pharmaceutical companies in commenting on FDA guidance documents and rulemaking as well as drafting and analyzing federal legislation.

Christina is a frequent contributor to Covington’s Digital Health and InsideMedicalDevices blogs.

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