Pharmaceutical company DaraBiosciences is the latest firm to receive an Untitled Letter from the US Food and Drug Administration's (FDA) Office of Prescription Drug Promotion (OPDP), the latest in a long line of recipients alleged to have promoted their products using materials with insufficient risk information.

Background

FDA's Untitled Letter-a stern admonition that nevertheless does not threaten or announce enforcement action for failure to comply with regulation(s)-refers to a promotional piece for DaraBiosciences' Soltamox (tamoxifen citrate), an orally administered breast cancer drug intended for patients whose tumors are estrogen receptor positive.

The drug, like many cancer therapies, is not without serious risks. FDA has assigned the drug a Black Box ("Boxed") Warning for adverse events which include uterine malignancies, stroke and pulmonary embolisms in certain instances. The labeling for the drug also includes a long list of other risks, including patients developing hypercalcemia, endometrial cancer, uterine sarcoma, non-malignant effects on the uterus, liver cancer, non-malignant effects on the liver, fetal harm and others.

Omitted Risk Information

The problem, FDA notes in its Untitled Letter to DaraBiosciences, is that you wouldn't know of many of these risks if you had only been exposed to the drug through a cited promotional piece.

The piece is intended to promote the drug's increased palatability over other drugs, with the company touting its liquid, "pleasant tasting" formulation and advantages over pill-based drugs, which can be more difficult to swallow for some patients. This, the piece implies, might increase rates of compliance over alternative FDA-approved therapies.

Unfortunately for the piece, it falls prey to a common error, one cited time and again by OPDP: While the benefits of the drug are listed in some detail in the promotional piece, the risks are not explained in full, and the reader is instructed to see the "full prescribing information" in a piece accompanying the advertising.

While the piece contained some important information, it omitted several important bits of information as well, FDA charged. "By omitting this important risk information, the sales aid misleadingly suggests that Soltamox is safer than has been demonstrated," FDA explained. Even the piece's statement to see the complete prescribing information "does not mitigate the misleading omission of important risk information in the sales aid," FDA added.

The company also failed to include "material facts" relevant to the "full approved indications" for the drug, FDA charged-a relatively uncommon allegation among Untitled Letters, which most often deal with too many statements of efficacy, not too few.

Tasty Enough to Improve Compliance?

Another common error was called out by OPDP's review staff: While the piece makes implied claims of superiority over other drugs because of the drug's liquid formulation, the company does not back these claims using substantial evidence or clinical experience.

"The totality of these claims and presentations suggests that, as a result of its liquid dosage form, Soltamox offers a therapeutic advantage over other available formulations of tamoxifen, including a positive impact on long-term patient compliance, adherence to treatment, patient preference, convenience, and treatment outcomes," FDA wrote.

Such claims require more substantial evidence than the research cited in the promotional piece, FDA stated. Claims that the drug could improve compliance are, at this time, simply speculation.

FDA requested that the company "immediately cease misbranding Saltamox" and submit a response to FDA by 7 January 2014.

Untitled Letter