Blog & Resources Camargo Blog January 29th, 2009

Watson’s 505(b)(2) Overactive Bladder Gel Approved by FDA

On 1/27/2009 Watson Pharmaceuticals announced that the FDA had approved its GELNIQUE(tm) (oxybutynin chloride) Gel 10% for the treatment of overactive bladder. The gel product supplements a transdermal patch made by Watson (Oxytrol) which has not had the marketing success one might expect, perhaps due to the acceptance of the patch form by patients.

So why the dermal route? What is the 505(b)(2) advantage? The first approved oxybutynin was Ditropan®, an oral, immediate-release product. Dry mouth is the major adverse event for this product, occurring in 60-80% of patients. Dry mouth is believed by many investigators to be caused by the metabolite of oxybutynin, the hepatic metabolism of oxybutynin to N-desethyloxybutynin (DEO). The development of Ditropan XL, an oral extended release formulation somewhat reduced the incidence of dry mouth but was not considered a solution. Hence, a product that delivers oxybutynin via the dermal route would largely bypass the hepatic metabolism. The following table compares the AE’s for the three products (note that the Ditropan XL data was obtained in a different study so direct comparison is not feasible).

Summary of Anticholinergic Adverse Events (%) Occurring in a Phase II Clinical Trial Evaluating the Efficacy and Safety of Oxybutynin TDS versus Oral Oxybutynin (IR)1and in Patients using Ditropan XL®, OROS® Technology (5-30 mg/day)2

**Oral IR** **(%)** **TDS** **(%)** **Ditropan XL** **(5-30 mg/day)**
Dry Mouth 82% 39% 60.8%
Constipation 50% 21% 13.1%
Nausea 26% 8% 8.9%
Blurred Vision 24% 18% 7.7%
1. Davila, G. W.; Daugherty, C. A.; Sanders, S. W. A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence. J Urol. 2001, 166, 140-145.
2. Alza Corporation. Ditropan XL (oxybutynin extended release tablets) Package Insert. 2000. Mountain View, CA, ALZA Corporation.

So, what is the incidence of dry mouth for Watson’s new gel? The web site for GELNIQUE indicates that 6.9% of the patients had dry mouth. The information posted does not include the percentage for patients on the placebo, but it appears that Watson has met its goal of having an OAB product with low AE’s.

Now that Watson’s OAB gel is approved, what happens with Antares’ OAB gel product in development? In 505(b)(2) drug development the first product that gets approved becomes the RLD for the other products in development – if the products are deemed by FDA to be the same. Antares hasn’t disclosed information about it’s product to determine if it is the same (it is described as a gel, but the concentration of oxybutynin is unknown).

OAB is characterized by a sudden, uncomfortable need to urinate with or without urge incontinence (urine leakage), and usually includes more frequent urination and nocturia (waking up at least once during the night to urinate).

Get Our Expertise Working for You

To learn how you can benefit from our regulatory and strategic development expertise, view our solutions or contact us.

Camargo Pharmaceutical Services provides comprehensive drug development solutions, specializing in customized programs including the 505(b)(2) pathway.

9825 Kenwood Road
Suite 203
Cincinnati OH, 45242
Durham Office
800 Taylor Street
Suite 101
Durham NC, 27701
Montreal Office
507 Place d'Armes
Suite 1101
Montreal, QC H2Y 2W8, Canada
Phone 513.561.3329
Toll Free 888.451.5708
Subscribe for our Latest Insights