OPDP Sends Six Warning and Untitled Letters in 2020 – Final Letter Sent to Azurity Pharmaceuticals
At the end of November 2020, the Office of Prescription Drug Promotions (OPDP) sent its sixth – and final – letter of the year to Azurity Pharmaceuticals for an email the company sent to doctors about its oral leukemia drug, Xatmep (methotrexate) used to treat pediatric patients with acute lymphoblastic leukemia as part of a multi-phase, combination chemotherapy maintenance regimen.
The OPDP takes issue with the email, stating it “makes false or misleading claims and/or representations about the risks and efficacy associated with Xatmep” and therefore “misbrands Xatmep within the meaning of the Federal Food, Drug and Cosmetic Act (FD&C Act) and makes its distribution violative.”
OPDP found the violations “especially concerning from a public health perspective” because Xatmep is not only used in a vulnerable pediatric patient population but also bears a Boxed Warning due to the possibility of serious and life-threatening risks, including embryo-fetal toxicity. The product labeling also includes warnings and precautions regarding bone marrow suppression, serious infections, renal toxicity, and increased toxicity with renal impairment, gastrointestinal toxicity, hepatic toxicity, pulmonary toxicity, hypersensitivity and dermatologic reactions, secondary malignancies, and ineffective immunization and risks associated with live vaccines.
The letter also references prior advisory comments made in 2017 to Silvergate Pharmaceuticals, Inc. (the initial company who received approval to market the drug, later acquired by CutisPharma and subsequently renamed Azurity Pharmaceuticals) though they are redacted from the untitled letter. When the letter resumes, it states that “Azurity appears to be promoting Xatmep without presenting the serious risks of the drug in a truthful and non-misleading manner, despite concerns previously expressed by OPDP.”
Additionally, OPDP takes issue with the statement made in the email that “Xatmep® (methotrexate) oral solution is available for your patients with Acute Lymphoblastic Leukemia” as it does not include the full approved indication for the drug, which is actually “the treatment of pediatric patients with acute lymphoblastic leukemia (ALL) as part of a multi-phase, combination chemotherapy maintenance regimen.”
OPDP also notes that the email prominently presents benefit claims for Xatmep in the body of the email in a bulleted list while the limited risk information provided (i.e., the Boxed Warning) is included only after the signature block, which typically signals the close or end of a correspondence, and therefore, the email fails to present the limited risk information with a prominence and readability reasonably comparable to the presentation of information relating to the benefits of the drug.
While the six letters sent in 2020 is below the 10 sent in 2019, it is just shy of the seven that were sent in 2018. It’s possible that the COVID-19 pandemic may have had an impact on the number of letters sent by OPDP in 2020 (no letters were sent between February 21, 2020 and August 14, 2020) it is also possible that OPDP will continue the slower pace of letters, as the agency grapples with fewer resources. However, smaller pharmaceutical companies should still be aware of the red tape and regulations involved in promoting pharmaceutical and device products.