FDA Advertising and Promotion Enforcement Activities: Update

FDA Advertising and Promotion Enforcement Activities: Update

July 22, 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. Beginning this year, alerts will be released on a quarterly basis.

In the first quarter of 2024 the Office of Prescription Drug Promotion (OPDP) posted the following untitled letter on FDA's website:

• Untitled Letter to Novartis Pharmaceuticals Corporation, re: NDA 209092, KISQALI® (ribociclib) tablets, for oral use, MA 1344 (January 18, 2024) (Kisqali Untitled Letter)

During the same period, 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) posted the following four warning letters.[1]

• Warning Letter to Dr. Joel Kaplan Inc. re: MegaVac Pump System, Metal Hand Pump System, STIMULATE: Red Light Therapy Wrap, DEEP: The Ultimate Penis Extender, and the Clitoris Enhancement System (January 8, 2024) (Dr. Joel Kaplan Inc. Warning Letter)
• Warning Letter to Soulaire Corporation re: External Counterpulsation Device Model: Soulaire (January 29, 2024) (Soulaire Corporation Warning Letter)
• Warning Letter to Trexo Robotics Holdings Inc. re Trexo Home and Trexo Plus (February 7, 2024) (Trexo Robotics Warning Letter)
• Warning Letter to Sol-Millennium Medical, Inc. re: sterile and non-sterile syringes and needles intended for aspiration and injection of medications and fluids into the body (March 18, 2024) (Sol-Millennium Medical, Inc. Warning Letter)

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)

Kisqali Untitled Letter (January 2024)

OPDP's untitled letter to Novartis Pharmaceuticals Corporation alleges that a TV ad misbrands Kisqali by making false or misleading representations about the drug's efficacy. Kisqali is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.

False or Misleading Claims About Efficacy

OPDP makes multiple allegations regarding the following claims based on the MONALEESA-2 clinical trial:

• "And KISQALI helps preserve quality of life so you're not just living, you're living well."
• "PRESERVES QUALITY OF LIFE[.]"
• "Quality of life was a secondary outcome measure of the trial. At a 26-month check-in, median time to worsening of at least 10% in quality of life score was 27.7 months with KISQALI + letrozole vs 27.6 months with placebo + letrozole. This analysis was not pre-planned to detect a false positive."

First, OPDP alleges that "[t]he claims that Kisqali 'preserves quality of life' and that patients taking the drug are 'living well' create a misleading impression that Kisqali has demonstrated a benefit on the patient reported outcome (PRO) measure of global quality of life (QoL)." OPDP states that the PRO data are "considered exploratory (i.e., hypothesis generating)."

Second, OPDP takes issue with the presentation of the 26-month check-in data from MONALEESA-2, again citing limitations to the relevant PRO analysis. Specifically, OPDP alleges that the PRO assessments may not have been frequent enough to collect data to support the claims and that the PRO endpoint of global QoL can be confounded by non-treatment and non-disease related factors. Additionally, OPDP states that "the study measured global QoL based on a 10% deterioration threshold with no confirmation of or justification for a 10% decrease in global health score being a meaningful deterioration specifically for patients with metastatic breast cancer who are undergoing treatment." OPDP also states that the sponsor "ha[s] not demonstrated that the time to deterioration endpoint, as assessed in [the] trial, is appropriate for evaluating PROs."

Third, OPDP alleges that the first claim above "presupposes that patients [were] 'living well' at trial baseline (i.e., before they beg[an] treatment with Kisqali), which is not necessarily the case for patients living with metastatic breast cancer and who have received prior lines of therapy." OPDP explains further that, because the exploratory PRO analyses in MONALEESA-2 were not designed to capture the concept of "living well," claims that patients who are taking Kisqali are "living well" are unsupported.

OPDP goes on to address the claim that patients taking Kisqali will "live longer" and similar claims and presentations, such as "[l]ong live family time," "[l]ong live dreams," "long live you," "[l]ong live hugs and kisses," and "long live life." OPDP acknowledges that two frames of the ad include a SUPER at the bottom that explains that "[o]verall survival (OS) was a secondary end point of the trial" and provides additional context on how OS was measured. However, OPDP states that the SUPER appears for only five seconds and "is more than twice the number of words, on average, than an adult can read within 5 seconds." OPDP states further that "the presentation of the SUPER is undermined by multiple, competing presentational aspects that distract the viewer from material information about the benefits of Kisqali and, therefore, creates a misleading impression about the drug's efficacy."

CDRH Office of Product Evaluation and Quality (OPEQ) and ORA Office of Medical Device and Radiological Health Operations (OMDRHO)

Dr. Joel Kaplan Inc. Warning Letter (January 8, 2024)

FDA's warning letter to Dr. Joel Kaplan Inc. (JKI), issued by OPEQ and OMDRHO, arose out of an inspection and alleges that four of the company's sexual health enhancement medical devices are being marketed outside the scope of the relevant 510(k) exemption. Specifically:

• The MegaVac Pump System and Metal Hand Pump System were listed under 21 CFR 876.5020 as external penile rigidity devices. By regulation, such devices are "intended to create or maintain sufficient penile rigidity for sexual intercourse." However, according to FDA, the product inserts and the firm's website claim that the products will cause an "increase in length and thickness," "correct mild penis curvature," and "lead to bigger, harder erections." FDA cites guidance stating that devices intended for penile enhancement, such as penis enlargement, and for treatment of diseases or conditions of the penis with respect to curvature, are outside the scope of the classification regulation at 21 CFR 876.5020. Therefore, FDA concludes that the exemption from premarket notification procedures does not apply to these JKI products.
• The STIMULATE: Red Light Therapy Wrap was listed under 21 CFR 890.5500 as an Infrared Therapeutic Heating Lamp, defined as being "a device intended for medical purposes that emits energy at infrared frequencies (approximately 700 nanometers to 50,000 nanometers) to provide topical heating." However, according to FDA, claims made on the firm's website "show an intent for use in the treatment of disease or other conditions." Specifically, FDA cites claims that the product will "[r]everse Penile Atrophy" and "maximize erection quality and size by boosting blood-flow, testosterone, and cellular repair."
• The DEEP: The Ultimate Penis Extender was listed under 21 CFR 890.3475 as a Limb Brace Orthosis "intended for medical purposes that is worn on the upper or lower extremities to support, to correct, or to prevent deformities or to align body structures for functional improvement." According to FDA, the product is wrongly classified because it is not used on an upper or lower extremity and, as per claims made on the firm's website, is intended for straightening penile curvature and treating Peyronie's disease.

In addition, FDA alleges that the Clitoris Enhancement System is a Class II device that requires premarket approval, citing claims on the firm website that the product will "use vacuum pressure to increase blood flow to the clitoral region and stimulate clitoral nerve endings to treat female sexual arousal disorder show[] an intent for use in the treatment of disease or other conditions." The letter indicates that FDA sent JKI a warning letter in 2014 regarding this device but that relevant concerns were not addressed.

Soulaire Corporation Warning Letter (January 29, 2024)

FDA's warning letter to Soulaire Corporation (Soulaire), issued by OPEQ, addresses Soulaire's external counterpulsation (ECP) device, marketed as an enhanced ECP (EECP) therapy. The device was cleared in 2020 under section 510(k) "for the treatment of chronic stable angina that is refractory to optimal anti-anginal medical therapy and without options for revascularization" as well as for "use in healthy patients to provide improvement in vasodilation and increased blood flow." FDA alleges that the firm is marketing the product for multiple intended uses outside of its original clearance, citing claims on the firm website that "EECP therapy by Soulaire has shown significant potential in managing Long Term Covid symptoms, particularly those related to heart health" and that "patients with diabetes often see improved pancreatic function," among others.

Additionally, FDA states that the device is misbranded because claims on the website offer the device for sale to "business[es],… home[s] or sports team[s]." which suggests the potential for sale and use of the device without physician oversight. The 2020 cleared labeling for the ECP states that the product is "intended for use under the oversight of a healthcare professional" and includes the Rx Only Caution statement indicating that "Federal law restricts this device to sale by or on the order of a physician." FDA concludes by stating that ECP devices intended for uses other than treatment of chronic stable angina that is refractory to optimal anti-anginal medical therapy and without options for revascularization are classified as class III and thus require premarket approval.

Trexo Robotics Holdings Inc. Warning Letter (February 7, 2024)

FDA's warning letter to Trexo Robotics Holdings, Inc. (Trexo), issued by OPEQ, arose out of an inspection. FDA alleges that the Trexo Home and Trexo Plus devices were marketed under the 510(k)-exempt classification regulation for isokinetic testing and evaluation systems, but that based on the firm's website and information obtained during the inspection, the Trexo devices are intended for uses different from and operate using different fundamental scientific technology than isokinetic testing and evaluation systems. FDA cited promotional claims that such devices could assist with ambulatory functions such as walking and standing.

Sol-Millennium Medical, Inc. Warning Letter (March 18, 2024)

FDA's warning letter to Sol-Millenium Medical, Inc. (SMM), issued by OPEQ and OMDRHO, arose out of an inspection, during which SMM provided a list of products purportedly covered under the 510(k) clearance for the company's Inviro Medical Luer Lock Syringe. That device was cleared "to inject medicines and vaccines into, or withdraw fluids from, the body."

FDA alleges that SMM is marketing syringes with substantially different technological characteristics, each of which requires a new 510(k). Of particular relevance is FDA's allegation that SMM is marketing syringes with a "low dead space claim." FDA states that "unsupported low dead space claims can result in patient harm such as dose inaccuracy and misleading users about the risk of disease transmission while using the device." FDA also alleges that SMM is promoting accessories, i.e., "devices intended for use with syringes," and that "[u]nsupported accessory device claims may lead to patient harm by increasing the existing risks of syringes when used together, including breakage, leaking, contamination, and dose inaccuracy."

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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