Toviaz is an oral drug developed by Pfizer for the treatment of overactive bladder. It contains the active ingredient fesoterodine fumarate, which is a muscarinic receptor antagonist that works by relaxing the bladder smooth muscle and inhibiting contractions. Clinical trials showed Toviaz significantly improved symptoms of urinary urgency, frequency, and incontinence compared to placebo. The FDA initially gave the drug an approvable rating in 2007 pending inspection of the manufacturing facility and labeling updates, which Pfizer addressed in their response leading to final approval in October 2008.

1. NDA # 22-030 Toviaz (Drug Development overview) -Viral Patel Course-Regulation of Drugs and Biologics UCSC Extension

2. Introduction Structure - Fesoterodine fumarate:

3. C’ntinue Sponsor: Pfizer Inc. Drug class : Anti muscarinic Indication : Overactive bladder with symptoms of urinary urgency, frequency and urge incontinence. Approved Formulations : 4 mg and 8 mg sustained-release tablets Route of administration : Oral Toviaz has not been studied in children.

4. Overview Over 33 million men and women have OAB problems. 1 in every 6 adults in USA . For Normal person : Nerves tells brains to go for urinate when bladder is full. For OAB patient : Nerves doesn’t wait of bladder to get full, it sends frequent signals means ‘false alarm’ to brain.

5. Mode of Action Fesoterodine -> Muscarinic receptor antagonist means it possess anti muscarinic activity.

6. C’ntinue Overactive bladder is due to smooth muscle contraction in bladder, which is too frequent and uncontrollable. Muscarinic receptor responsible for contraction of urinary bladder smooth muscle and stimulation of salivary secretion. So, Fesoterodine’s anti muscarinic activity inhibits Muscarinic receptor. By this way fesoterodine produce its effects by relaxing smooth muscle of the bladder.

7. Clinical Study ‘‘ Toviaz success is mainly based on, a twelve week randomized placebo controlled ,Phase 3 trials in which Fesoterodine shows statistically significant and clinically meaningful improvement compared to placebo’’,according to FDA. For the combined study,554 subjects received placebo,554 subjects received 4 mg/day and 566 subjects received 8 mg/day study drug.

8. continue 8 mg Fesoterodine arm demonstrated upto an 88 percent median reduction in urge urinary incontinence compared with placebo.

9. Approval History NDA Submission : NDA submitted on March 2006 -> FDA respond on January 2007 ‘Approvable’ (two conditions) -> Pre-approval inspection of API manufacturing facility (Because site has not been available for PAI ) -> Labeling and safety data

10. 2. Complete response to FDA’s Approvable letter on May 01,2008. -> Pfizer received Approval letter on October 31,2008 . PDUFA goal date was Nov 02,2008