Feb. 23, 2021 – Amid a surge in opioid overdose deaths over the past year – due in part to the ongoing COVID-19 pandemic and its corresponding isolation and lack of employment and support services – the FDA’s Office of Prescription Drug Promotion (OPDP) has asserted the agency’s “ongoing commitment to combat inappropriate opioid use.”
This FDA statement was included in a Feb. 16 press release announcing a Feb. 11 Warning Letter OPDP issued to AcelRx for making false and misleading claims about the risks and benefits of Dsuvia®, a potent opioid analgesic.
Dsuvia, which is indicated for the management of acute pain in adults that is severe enough to require and opioid analgesic and for which alternative treatments are inadequate, had been approved with a Risk Evaluation and Mitigation Strategy (REMS) that reflects the serious risks associated with the product, which include respiratory depression and death.
Center for Drug Evaluation and Research (CDER) officials have indicated that promotional claims made for opioids will be scrutinized by the agency. In a recent “CDER Conversation” with OPDP Acting Director Katie Gray, Pharm.D., she noted that OPDP focuses its resources on promotional materials for high-risk drugs, such as opioids.
“We want to make sure the promotional materials accurately convey the risks associated with these drugs, convey responsible use of opioids, and do not inadvertently contribute to the opioid epidemic,” Gray stated. As the pandemic heads into year two, there are concerns that the opioid epidemic may become even worse.
As reported in a Nov. 28, 2020, article in Politico, “more than 76,000 people died of a drug overdose between April 2019 and April 2020, according to the most recent preliminary federal data, the most ever recorded during a 12-month period,” and the numbers of deaths caused by opioids during the past year are expected to rise.
As such, the stakes for FDA’s stance that promotional materials be truthful and non-misleading are even higher for opioid products. “Opioid products are highly addictive controlled substances and there are serious public health risks associated with their use, including addiction, abuse, and misuse, that can lead to overdose and death,” according to the FDA press release.
“False and misleading claims can negatively impact prescriber awareness and understanding about approved opioid drugs, their risks, and the actions and precautions necessary for the safe use of these products,” the press release states.
In the Warning Letter to AcelRx, OPDP cites a Dsuvia banner ad and tabletop display for using a “Tongue and Done” claim that the agency says is misleading because it implies “that the administration of Dsuvia consists of a simple, one-step process, when this is not the case. In fact, there are numerous administration steps outlined in the PI, including a separate, distinct step to visually confirm tablet placement in the patient’s sublingual space of the mouth.”
In its press release, the FDA states that “critical conditions for the safe use of Dsuvia are not appropriately conveyed in the promotional communications” cited in the Warning Letter, which specifies that Dsuvia is indicated for use “in a certified medically supervised healthcare setting, such as hospitals, surgical centers, and emergency departments.”
AcelRx also is cited for claims that create a misleading impression about the dosing and administration of Dsuvia, and for failing to present information “related to the drug’s Boxed Warning, Contraindications, Warnings and Precautions, and Adverse Reactions for Dsuvia with a prominence and readability reasonably comparable” with the presentation of information relating to its benefits in the banner and display.
Further, although the banner ad provided the healthcare settings in which Dsuvia should be administered and the Important Safety Information (ISI), this information is only seen when scrolling and is “intermingled with risk information in a paragraph format in a much smaller font size and a plain white background,” unlike the benefit information, which is presented in a color background and a larger font.
“Therefore, this does not mitigate the misleading impression,” according to the Warning Letter, which also lists the factors that impact prominence and readability.
OPDP calls for AcelRx to cease these alleged violations, submit a written response to the agency addressing its concerns, listing all promotional materials for Dsuvia that contain similar claims and when they will be discontinued, and conduct corrective communications.
The AcelRx Warning Letter is the first Warning Letter and only enforcement letter issued by OPDP to date in 2021. In 2020, OPDP issued just four Warning Letters and two Untitled Letters.