Bhavana Desai
Senior Director, Advertising and Promotional Compliance
Allergan, Inc. 
2525 Dupont Drive
P.O. Box 19534
Irvine, CA 92623-9534

RE:   NDA # 021275
        Lumigan^®(bimatoprost ophthalmic solution)
        0.03% MACMIS #18925

Dear Ms. Desai:

The Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed a professional “Direct Mail” (APC20SP09) (Direct Mail) for LUMIGAN^® (bimatoprost ophthalmic solution) 0.03% (Lumigan) submitted by Allergan, Inc. (Allergan) under cover of Form FDA 2253.  The Direct Mail is false or misleading because it makes unsubstantiated superiority claims.  Therefore, the Direct Mail misbrands Lumigan in violation of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 352(a). Cf. 21 CFR 202.1 (e)(6)(ii) & (e)(7)(i). 

Background

According to its FDA-approved product labeling (PI)¹ :

LUMIGAN^® is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension. 

Unsubstantiated Superiority Claims

Promotional materials are misleading if they contain representations or suggestions that a drug is safer or more effective than another drug when this has not been demonstrated by substantial evidence or substantial clinical experience.  The Direct Mail contains the following claims and presentation comparing Lumigan to latanoprost:

•  "When your PGA patients need a change... Steady CONTROL that lasts" - "Prescribe LUMIGAN^® for proven IOP lowering and tolerability after latanoprost”

•  “As presented by Jason Bacharach, MD, et al at the 19th Annual Meeting of the American Glaucoma Society, this large, randomized, well-controlled latanoprostreplacement trial found ... LUMIGAN^® was able to achieve low target IOP levels after latanoprost”

•  “Recent Data Presented at AGS – See what the latest latanoprost-replacement trial revealed about bimatoprost efficacy after latanoprost ...  Results from a large, randomized, well-controlled latanoprost-replacement trial”

•  “When your PGA patients need a change, consider ... LUMIGAN^® efficacy after latanoprost”

•  Bar graph titled, “Patients Reaching Specific IOP Levels at Week 18” showing up to 91.9% of Lumigan patients versus 85.3% of latanoprost patients achieved less than or equal to 20 IOP (mm Hg) and Bar graph claim, “Baseline mean diurnal IOP was comparable between groups: 21.9 mm Hg for LUMIGAN^® and 22.2 mm Hg for latanoprost (P = .106)”

These claims and presentation misleadingly imply that treatment with Lumigan is superior to treatment with latanoprost in that Lumigan will be effective after latanoprost stops working or when latanoprost is no longer effective in adequately lowering intraocular pressure (IOP), when this has not been demonstrated by substantial evidence or substantial clinical experience.  Superiority claims for drugs with an IOP-lowering indication should be supported by two adequate and well-controlled, head-to-head trials comparing the IOPlowering effect of each drug at all time points tested over at least 12 weeks.  The primary efficacy variable utilized in the cited study^2,3 [the change from baseline (day 1) in mean diurnal IOP at the week 12 and week 18 visits] does not constitute substantial evidence because it is an average of all the IOP time points tested (i.e., 8 am, 12 pm, and 4 pm).  Therefore, claims implying that Lumigan has demonstrated superior efficacy to latanoprost based on this study are misleading. 

Conclusion and Requested Actions

For the reasons discussed above, the Direct Mail misbrand Lumigan in violation of the Act, 21 U.S.C. 352(a). Cf. 21 CFR 202.1 (e)(6)(ii) & (e)(7)(i). 

DDMAC requests that Allergan immediately cease the dissemination of violative promotional materials for Lumigan such as those described above.  Please submit a written response to this letter on or before December 3, 2010, stating whether you intend to comply with this request, listing all promotional materials (with the 2253 submission date) for Lumigan that contain violations such as those described above, and explaining your plan for discontinuing use of such violative materials.  Please direct your response to me at the Food and Drug Administration, Center for Drug Evaluation and Research, Division of Drug Marketing, Advertising, and Communications, 5901-B Ammendale Road, Beltsville, MD 20705-1266, facsimile at 301-847-8444.  In all future correspondence regarding this matter, please refer to MACMIS # 18925 in addition to the NDA number.  We remind you that only written communications are considered official. 

The violations discussed in this letter do not necessarily constitute an exhaustive list.  It is your responsibility to ensure that your promotional materials for Lumigan comply with each applicable requirement of the Act and FDA implementing regulations. 

Sincerely,

Carole C. Broadnax, R.Ph., Pharm.D. 
Regulatory Review Officer
Division of Drug Marketing,
Advertising, and Communications

__________________________________________________

^' The approved PI submitted with the Direct Mail on Form FDA 2253 (and the version referred to in this letter) was dated September 2006.  Although not relevant to the issues cited in this letter, the most recent version of the Lumigan PI is dated August 2010. 
² Bacharach J, Schenker HI, Caprioli J, Liu C, Batoosingh AL.  Masked, randomized, parallel comparison of IOP-lowering efficacy after switching to bimatoprost 0.03% vs continuing with latanoprost 0.005%.  Poster presented at: 19th Annual Meeting of the American Glaucoma Society (AGS); March 5-8, 2009; San Diego, CA. 
3 Data on File, Allergan, Inc.; 192024-034-00.