Alcon, Inc., Fort Worth, TX, Oct. 20 (DDMAC).

DDMAC, in consultation with the Division of Anti-Infective and Ophthalmology Products, reviewed a professional sales aid for Alcon's Nevanac (nepafenac ophthalmic suspension) and determined the sales aid to be misleading because it broadened the indication, presented unsubstantiated superiority claims, overstated the efficacy of Nevanac, omitted risk information, and presented misleading safety claims, including a dosing claim that was inconsistent with the FDA-approved product labeling or insert (PI) for Nevanac.

FDA objected to the Alco sales aid because it suggested that Nevanac is effective in a broader range of patients than has been demonstrated by substantial evidence or substantial clinical experience. Specifically, on page three, the sales aid stated: "Administration of nepafenac 0.1% suspension leads to significant suppression of PGEZ synthesis in the posterior portion of the eye." This claim, the agency emphasized, is misleading because it suggested that Nevanac is effective for treating ocular conditions involving the posterior portion of the eye (e.g., macular edema).

DDMAC added that the aforementioned issue is compounded by the following statement on the last page of the sales aid: "Prescribe Nevanac suspension for excellent postoperative pain and inflammation control." DDMAC felt that this claim also was misleading because it suggested that the drug was effective for post-operative pain and inflammation after any eye surgery.

Moreover, the agency took issue because the sales aid misleadingly suggested "that Nevanac is superior to other drug therapies when this has not been demonstrated by substantial evidence or substantial clinical experience." Specifically, on page three, the marketing piece contained a graph comparing the prostaglandin reduction in the vitreous humor of Nevanac with two other drugs in its class--diclofenac and ketorolac. FDA said it is not aware of substantial evidence or substantial clinical experience that demonstrates the superiority of Nevanac over these two ophthalmic NSAIDS in post-operative pain and inflammation or prostaglandin inhibition. In fact, FDA is not aware of any comparison trials between Nevanac and any other ophthalmic NSAID. According to the warning letter, Nevanac was approved based on comparison to its vehicle, without any comparison to other active agents.

FDA further objected to overstatements of efficacy contained in the Alcon sales aid, such as, on page three, a graph entitled "Percent Clinical Cures By Visit" next to which there was a bullet stating ">80% experienced clinical cures without use of steroids." According to the warning letter, this presentation is misleading because the clinical cure rates presented in the graph are greater than has been demonstrated by substantial evidence or substantial clinical experience.

Furthermore, although the sales aid contained information regarding the contraindication and most common and less severe AEs, it failed to communicate the most serious warnings and precautions associated with Nevanac therapy, such as, the potential for cross-sensitivity reactions, increased bleeding times, delay of healing, keratitis and other corneal AEs.

The agency also noted that safety presentations in the sales aid were misleading as well. For example, page four presented the claim: "The excellent safety of Nevanac suspension has been demonstrated in vivo at concentrations up to 1.5%, dosing regimens up to eight drops daily, and at periods up to six months."

According to DDMAC, this claim is misleading because the references cited to support it were studies conducted in animals. Moreover, such a suggestion was inconsistent with the PI, which recommended use of the 0.1% suspension three times daily for one day prior to surgery, continued on the day of surgery and through the first two weeks of the postoperative period for the treatment of pain and inflammation. The PI also contained a precaution stating that use beyond 14 days post surgery may increase patient risk for occurrence and severity of corneal AEs.

Finally, page four of the sales aid also contained the claim: "Proven safe and well tolerated throughout in vivo ocular tissues with no delays in wound healing." FDA pointed out that this claim was misleading because it directly contradicted the Precautions section of the PI, which contained the general precaution that NSAIDS, including Nevanac, may slow or delay healing. F-B, Lab; Doc. 13980W