FDA Sends Watson Letter Over Gelnique Promotion
SILVER SPRING, Md., Dec. 9, 2010 - The FDA today posted on its website a letter sent to Watson Pharmaceuticals regarding a promotion for its overactive bladder treatment Gelnique. The letter is below.
Wendy DeSpain, B.S., M.B.A., R.A.C. Associate Director, Proprietary Regulatory Affairs Watson Pharmaceuticals, Inc. 577 Chipeta Way Salt Lake City, UT 84108
RE: NDA #022204
GELNIQUE (oxybutynin chloride) 10% gel
MACMIS #19271
Dear Ms. DeSpain:
The Division of Drug Marketing, Advertising, and Communications (DDMAC) of the U.S. Food and Drug Administration (FDA) has reviewed Watson Pharmaceuticals, Inc.’s (Watson) ACOG 2010 Restroom Stall Cling (Part No. 06326) (stall cling) for its drug product, GELNIQUE (oxybutynin chloride) 10% gel (Gelnique). The stall cling was viewed at the American College of Obstetricians and Gynecologists annual clinical meeting held on May 15-19, 2010, in San Francisco, CA. The stall cling is misleading because it minimizes the risks of Gelnique, overstates its efficacy, broadens its indication, omits important risk information, and makes unsubstantiated claims for the drug. Thus, the stall cling misbrands Gelnique in violation of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 352(a) & 321(n) and FDA implementing regulations. 21 CFR 1.21(a); cf. 21 CFR 202.1(e)(5)(i), (iii); (e)(6)(i) & (e)(7)(viii).
Background
According to its FDA-approved product labeling (PI), Gelnique is
indicated for the treatment of overactive bladder with symptoms of
urge urinary incontinence, urgency, and frequency.
Gelnique is contraindicated in patients with urinary retention,
gastric retention, uncontrolled narrow-angle glaucoma, and known
hypersensitivity to Gelnique, including skin hypersensitivity.
Gelnique also has warnings and precautions regarding use in
patients with clinically significant bladder outflow obstruction,
gastrointestinal disorders, and myasthenia gravis; as well as risks
of skin hypersensitivity and skin transference. In addition, the
drug is an alcohol-based gel and is therefore flammable. The most
common adverse events in the randomized, double-blind,
placebo-controlled, 12-week study (>2% and > placebo) for
Gelnique- and placebo-treated patients were dry mouth (7.5% vs
2.8%), urinary tract infection (6.9% vs 4.3%), application site
reactions (5.4% vs 1.0%), upper respiratory tract infection (5.4%
vs 5.0%), dizziness (2.8% vs 1.0%), nasopharyngitis (2.8% vs 2.3%),
fatigue (2.1% vs 1.0%), and viral gastroenteritis (2.1% vs 1.8%).
Application site reactions included
Reference ID: 2870133 Wendy DeSpain, B.S., M.B.A., R.A.C Page 2
Watson Pharmaceuticals, Inc. NDA #022204/MACMIS #19271
application site pruritus, dermatitis, papules, anesthesia,
erythema, irritation, pain and papules.
The Clinical Studies section of the PI states that the efficacy and
safety of Gelnique were evaluated in a single, randomized,
double-blind, placebo-controlled, parallel-group, 12-week study.
Gelnique-treated patients experienced a statistically significant
decrease in the number of urinary incontinence episodes per day
from baseline to endpoint (the primary efficacy endpoint) compared
with placebo (p<0.0001). Mean and median change from baseline in
daily incontinence episodes between Gelnique- and placebo-treated
patients are shown below:
* Last-Observation-Carried-Forward statistical imputation for
missing data.
Minimization of Risk
Promotional materials are misleading if they fail to present risk
information with a prominence and readability reasonably comparable
with the presentation of information relating to the effectiveness
of the drug, taking into account all techniques apt to achieve
emphasis.
The stall cling very prominently presents efficacy claims and
presentations in large, bold, and colorful font and graphics,
including an image of a woman holding her hands in a
“pistol” position with Gelnique on her fingertips,
surrounded by a significant amount of space. In contrast, the risk
information is relegated to the bottom of the piece and written in
white text on a purple background in an extremely small font size
and in single-spaced paragraph format, making this information very
difficult to read. This presentation misleadingly minimizes the
serious risks associated with Gelnique because it fails to convey
this important risk information with a prominence and readability
reasonably comparable to the claims of effectiveness in the piece.
In addition, the most common adverse events are presented before
more serious risks. The overall effect of this presentation greatly
undermines the communication of important risk information,
minimizes the risks associated with Gelnique, and misleadingly
suggests that the drug is safer than has been demonstrated.
Reference ID: 2870133 Wendy DeSpain, B.S., M.B.A., R.A.C Page 3
Watson Pharmaceuticals, Inc. NDA #022204/MACMIS #19271
Overstatement of Efficacy
Promotional materials are misleading if they represent or suggest
that a drug is more effective than has been demonstrated by
substantial evidence or substantial clinical experience.
The stall cling contains the headline claim, “Smart gel
technology is her weapon against wetting” with a graphic of a
woman holding her hands in a “pistol” position with
Gelnique on her fingertips, and the claim “Significant
reduction in incontinence episodes (P<0.0001)
71%.” (emphasis in original; references omitted) The bottom
corner of the stall cling contains a footnote in extremely small
font size, “Represents median change from baseline. Reduction
with placebo was 55.6%.” The totality of this presentation is
misleading because it overstates the efficacy of Gelnique therapy
by omitting material information about the drug. Specifically, the
pivotal trials that supported approval of Gelnique reported a
reduction in incontinence episodes of 2.0 per day in
placebo-treated patients and 2.7 per day in Gelnique¬treated
patients, for a difference of <1 daily incontinence episode
between the treatment groups. The presentation cited above
overstates the magnitude of this effect by failing to disclose this
information. Additionally, the inclusion of the footnote,
“Reduction with placebo was 55.6%” in extremely small
font size in the bottom corner of the stall cling does not mitigate
this misleading presentation.
Broadening of Indication
Promotional materials are misleading if they suggest that a drug is
useful in a broader range of conditions or patients than has been
demonstrated by substantial evidence or substantial clinical
experience.
The stall cling prominently presents the claims, “Smart gel
technology is her weapon against wetting” and
“Significant reduction in incontinence episodes. . . .”
(bolded emphasis in original; underlined emphasis added) These
claims are misleading because they imply that Gelnique is useful in
a broader range of conditions or patients (i.e., for all types of
incontinence) than has been demonstrated by substantial evidence or
substantial clinical experience. According to the Indications and
Usage section of the PI, Gelnique is indicated for the treatment of
overactive bladder with symptoms of urge urinary incontinence,
urgency, and frequency. We note that Gelnique’s full
indication is presented at the bottom of the piece above the
“Important Safety Information.” However, the full
indication is far removed from the above misleading claims.
Additionally, the presentation of the full indication is written in
white text on a purple background in an extremely small font size
in single-spaced format, making this information very difficult to
read. In contrast, the above misleading claims and the accompanying
graphic are presented very prominently and can be easily seen by
viewers of this piece. Therefore, this presentation undermines the
communication of Gelnique’s indication and does not mitigate
these misleading claims.
Reference ID: 2870133 Wendy DeSpain, B.S., M.B.A., R.A.C Page 4
Watson Pharmaceuticals, Inc. NDA #022204/MACMIS #19271
Omission of Risk Information
Promotional materials are misleading if they fail to reveal facts
that are material in light of the representations made by the
materials or with respect to consequences that may result from the
use of the drug as recommended or suggested by the materials.
The stall cling is misleading because it omits the following
important material facts from the Gelnique PI (in pertinent part;
emphasis in original):
WARNINGS AND PRECAUTIONS
. . .
Skin Hypersensitivity
In a controlled clinical trial of skin sensitization, 1 of 200
patients (0.5%) demonstrated
skin hypersensitivity to GELNIQUE. Patients who develop skin
hypersensitivity to
GELNIQUE should discontinue drug treatment.
Unsubstantiated Claims
The stall cling contains the claim, “Fits into a
woman’s skin care routine. . . .” (emphasis in
original) This claim is misleading because it implies that the drug
will not interfere with a patient’s daily skin care routine
(as part of her daily activities), when such has not been
demonstrated by substantial evidence. There are multiple
considerations for use as discussed in the Contraindications,
Warnings and Precautions, and Adverse Reactions sections of the PI,
and detailed instructions for use as described in the Dosage and
Administration and Information for the Patient sections of the PI.
For example, the PI describes the risks of skin hypersensitivity
and application site reactions whose occurrence and management do
not necessarily “fit into a woman’s skin care
routine.” Also, the PI provides step-by-step instructions on
how to apply the gel correctly, including avoiding bathing,
swimming, showering, exercising, or immersing the treated area in
water for one hour after application, and avoiding covering the
treated area with clothing until the gel has dried. Therefore, the
claim, “Fits into a woman’s skin care routine” is
not face-valid. Additionally, we note that there are no references
cited to support this claim. Substantial evidence, as demonstrated
through adequate and well-controlled trials using well-developed
instruments, is necessary to support the suggestion that the
administration of Gelnique will not interfere with a woman’s
skin care routine as part of her daily activities.
Furthermore, the stall cling presents the headline claim,
“Smart gel technology is her weapon against wetting.”
(bolded emphasis in original; underlined emphasis added) This claim
is misleading because it implies that Gelnique’s gel
formulation offers a distinct effectiveness or other advantage over
other overactive bladder treatments. We are not are of substantial
evidence or substantial clinical experience to support this claim.
As described above, there is a difference of <1 daily
incontinence episode between Gelnique-and placebo-
Reference ID: 2870133 Wendy DeSpain, B.S., M.B.A., R.A.C Page 5
Watson Pharmaceuticals, Inc. NDA #022204/MACMIS #19271
treated patients. If Watson has any data supporting the implication
that Gelnique’s gel formulation offers an advantage over
other treatments for overactive bladder, please submit them to FDA
for review.
Conclusion and Requested Action
For the reasons discussed above, the stall cling misbrands Gelnique
in violation of the Act 21
U.S.C. 352(a) & 321(n) and FDA implementing regulations. 21 CFR
1.21(a); cf. 21 CFR 202.1(e)(5)(i), (iii); (e)(6)(i) &
(e)(7)(viii).
DDMAC requests that Watson immediately cease the dissemination of
violative promotional materials for Gelnique, such as those
described above. Please submit a written response to this letter on
or before December 13, 2010, stating whether you intend to comply
with this request, listing all promotional materials (with the 2253
submission date) for Gelnique 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 #19271 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 Gelnique comply with each
applicable requirement of the Act and FDA implementing
regulations.
Sincerely,
{See appended electronic signature page}
Michelle Safarik, MSPAS, PA-C Regulatory Review Officer Division of
Drug Marketing, Advertising, and Communications
Reference ID: 2870133
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This is a representation of an electronic record that was signed
electronically and this page is the manifestation of the electronic
signature.
/s/
MICHELLE L SAFARIK 11/30/2010
Link to promotional material
Posted: December 2010
