OPDP Issues Enforcement Letter for Investigational Drug Promotion

April 30, 2019 – In its first enforcement letter of 2019, the FDA’s Office of Prescription Drug Promotion (OPDP) asserts that an article posted on a sponsor’s website misbrands the investigational drug “Sodium Acetate C-11” (11-C Acetate) because it suggests in a promotional context that the drug is safe and effective for the purpose for which it is being investigated – as a PET scan agent for detecting recurrent prostate cancer.

“This is another reminder that sponsors must scrupulously avoid presenting an investigational drug as though its safety and effectiveness have been approved. It is notable that about half of enforcement letters over the past few years have been for unapproved drugs,” stated Coalition for Healthcare Communication Executive Director Jon Bigelow.

The claims at issue were included in an article about current and emerging PET/CT techniques used for screening for recurrent prostate cancer on a blog by Phoenix Molecular Imaging Center Medical Director Dr. Fabio Almeida, M.D.

Trials for 11-C Acetate are being conducted at Phoenix, according to the website, and OPDP states that Almeida is the sponsor and principal investigator for the investigational new drug. “Your webpage describes 11C-Acetate as a useful PET scan agent for detecting recurrent prostate cancer. This use is one for which a prescription would be needed because it requires the supervision of a physician and, thus, adequate directions for lay use cannot be written,” the Feb. 15 Untitled Letter states.

Although investigational drugs are exempt from being misbranded for a lack of “adequate directions for use,” FDA regulations stipulate that sponsors and investigators “shall not represent in a promotional context that an investigational new drug is safe or effective for the purposes for which it is under investigation or otherwise promote the drug.” OPDP alleges that promoting 11-C Acetate as safe and effective for the purpose for which it is being investigated when it has not yet been approved is a failure to comply with the terms of the exemption.

A few of the claims that the OPDP states misbrand 11-C Acetate include:

  • “11C-choline and 11C-acetate are lipid metabolism PET agents. Both of these agents are useful for detecting recurrent disease after a PSA [prostate-specific antigen] relapse.”
  • “Small direct comparison studies of 11C-acetate and 11C-choline have revealed no clear clinical differences between these agents, although a few studies have suggested a higher detection rate of local recurrences and small pelvic lymph node metastases with 11C-acetate.”
  • “In some patients, the muscle uptake of Axumin [(fluciclovine F 18)] may be so high as to render the study non-diagnostic, despite having properly abstained from physical activity prior to the scan. Additionally, in a small but significant number of patients, interfering urinary excretion is seen. These factors likely help explain the apparent lower performance of this agent compared to 11C-Acetate and Choline.”
  • “The lack of urinary tracer excretion of 11C-Acetate allows visualization of small and subtle lesions in this region, not typically possible with PSMA [prostate-specific membrane antigen] based agents.”

The OPDP concludes in the enforcement letter that these and other claims make statements about the safety and efficacy of 11-C Acetate and “suggest in a promotional context that 11-C Acetate, an investigational new drug, has been shown to be different from or superior to approved therapies for PET imaging.

And, although the webpage states that 11-C Acetate is “available under expanded access clinical trials at multiple institutions,” OPDP finds that this language “neither adequately conveys that the product is unapproved, nor sufficiently mitigates impressions conveyed by other presentations that 11C-Acetate is safe and effective for any use.” Further, OPDP states that the claims made are misleading, “especially considering the serious nature of disease recurrence and the need for early detection.”

In summary, the OPDP states that “the above cited claims and presentations on the webpage represent the drug as having an established role in the PET imaging of prostate cancer, when 11C-Acetate has not been proven to be safe and effective within the meaning of the FD&C Act and has not been approved as a drug under that authority for any use.”