DDMAC Issues Two Untitled Letters Focusing on Comparative Claims and the Need for Substantial Evidence; A Momentary Departure From Past Practice or a Sign of Things to Come?

May 22, 2007

As we previously reported, FDA’s Division of Drug Marketing, Advertising, and Communications (“DDMAC”) has, in the past year, focused its efforts on ensuring that promotional pieces contain proper presentations of safety data and appropriate efficacy claims.  Two new Untitled Letters from DDMAC, however, illustrate that safety issues are not DDMAC’s sole focus; companies also need to support any comparative efficacy and superiority claims with substantial evidence. 

On May 9, 2007, DDMAC issued two Untitled Letters, one concerning a detail aid for GlaxoSmithKline’s FLONASE (fluticasone propionate) Nasal Spray, 50 mcg and the other regarding a detail aid for Schering Corporation’s NASONEX (mometasone furoate monohydrate) Nasal Spray, 50 mcg.  FLONASE and NASONEX are approved for seasonal allergic and perennial allergic rhinitis in certain patients. 

According to DDMAC’s Untitled Letters, the detail aids misbrand the drugs in violation of the FDC Act §§ 502(a) and 201(n) because:

  • Both detail aids make unsubstantiated superiority claims that misleadingly imply that each drug is superior to the other;
  • Both detail aids use the word “congestion” when neither drug is specifically indicated for congestion, thus overstating their efficacy; and
  • The FLONASE detail aid fails to reveal a material fact in that it does not contain the full, approved indication. 

Superiority Claims

DDMAC found that the superiority presentations in the FLONASE detail aid are misleading because the cited reference does not constitute “substantial evidence” for two reasons.  First, the study design did not clearly plan a head-to-head trial (it originally contemplated a placebo-controlled trial of FLONASE and, therefore, it is difficult to determine the significance of the comparison finding).  Second, the study was not replicated, and typically superiority claims should be based on comparisons of the two drug products in two adequate, well-designed, head-to-head clinical trials.

DDMAC found that the superiority presentations for NASONEX in the detail aid are misleading because they are based on patient responses to a single question in the “overall preference questionnaire” that assessed 8 product sensory attributes.  DDMAC found that the use of a response to a single question is insufficient to support the broad concept of overall patient preference.  DDMAC also stated that patient preference claims should be derived from well-designed and controlled head-to-head studies using well-developed instruments that can evaluate patient preference.  Further, DDMAC found a graph in the NASONEX detail aid to be misleading in that it only presented favorable results from the preference questionnaire, when NASONEX only received favorable results for half of the questions. 

Overstatement of Efficacy

DDMAC cited both detail aids for highlighting “congestion” when the drugs are approved, in relevant part, for seasonal allergic rhinitis.  The indication, “seasonal allergic rhinitis” is based on studies reviewing results of both FLONASE and NASONEX on a composite of several symptoms that may have included congestion as one of those symptoms.  These results are referred to as a total nasal symptoms score (“TNSS”).  DDMAC stated that because the primary efficacy endpoint of the studies for both drugs was on TNSS, the studies do not represent a clear effect on any individual TNSS component.

DDMAC’s Untitled Letters to Glaxo and Schering are consistent with previous enforcement letters addressing comparative claims, but are an interesting departure from DDMAC’s practices in the past year in that they do not cite to the omission or minimization of risk information.  As we previously reported, in 2006, of the 22 Enforcement Letters issued by DDMAC, only one did not cite the omission or minimization of risk as a violation. 

By Dara Katcher Levy

Categories: Enforcement