Even sponsors not aiming for the benign prostatic hyperplasia market should take notice of the Oct. 8 approval of Watson Pharmaceuticals' Rapaflo (silodosin).

The on-time, first-cycle approval of a me-too drug in a crowded class could indicate a regulatory environment not as black and white as current conditions seem to indicate.

The selective alpha-1 adrenergic receptor antagonist was approved to treat the signs and symptoms of BPH, a disease characterized by urination problems including decreased urine flow, more frequent urination and nocturia.

The alpha blocker will compete directly with products including GlaxoSmithKline's Avodart (dutasteride), Pfizer's Cardura XL (doxazosin extended-release), finasteride (Merck's Proscar and generics), and Boehringer Ingelheim's Flomax (tamsulosin).

Watson plans to launch Rapaflo in early 2009, aiming to differentiate it from existing treatments by highlighting its unique selectivity (¹ Also see "Phase III Results Buoy Watson’s Benign Prostatic Hyperplasia Candidate" - Pink Sheet, 16 January, 2007.).

According to the firm, Rapaflo's preferential binding to alpha-1A receptors maximizes efficacy, while its lower binding affinity for the alpha-1B receptors minimizes cardiovascular side effects, such as drops in blood pressure and dizziness.

Improved tolerability, by way of greater specificity, is often used as a point of differentiation for a me-too product entering a crowded market. Tolerability has been a primary marketing message for Forest/Mylan's Bystolic (nebivolol), which in late 2007 became the 19th beta blocker to clear FDA (² Also see "Forest Hopes Efficacy In Blacks And Tolerability Will Set Bystolic Apart" - Pink Sheet, 7 January, 2008., p. 5).

Sales Force To Tackle Growing Urology Portfolio

The Rapaflo approval is the first of possibly three urology products that could be approved for Watson in the next 18 months.

The firm's oxybutynin gel product for overactive bladder has a PDUFA date in late January, meaning Watson may face multiple product launches simultaneously.

"Given that we got an outright approval in 10 months - which is pretty unique these days - we'll have to evaluate a little further how we deploy the sales force on [Rapaflo]," Watson Executive Director-Investor Relations Patty Eisenhaur said.

The firm has a urology sales force of about 100 reps, and may have to call on its 120-rep specialty field force - which calls on gynecologists and high-prescribing urologists - if the oxybutynin gel product is approval on time.

The company also has plans to file an sNDA later this year for a six-month formulation of its prostate cancer treatment Trelstar (triptorelin); currently marketed formulations include Trelstar LA, given as a shot every 12 weeks, and Trelstar Depot, injected once every four weeks.

Rapaflo's approval was based on two Phase III, 12-week, placebo-controlled trials in 923 patients with signs and symptoms of BPH, as well as a 40-week open-label study. In the two placebo trials, 8 mg once-daily Rapaflo for 12 weeks resulted in significant and rapid relief of BPH symptoms compared to placebo, as measured by the International Prostate Symptom Score. IPSS includes irritative (frequency, urgency, and nocturia) and obstructive (hesitancy, incomplete emptying, intermittency, and weak stream) symptoms.

Rapaflo was also proven to significantly improve Qmax scores (maximum urine flow rates) as early as two hours following first dose and at 12 weeks of treatment.

BPH Market Leader Goes Generic In 2010

Pricing for Rapaflo has not yet been determined, the company said.

The U.S. market for BPH is estimated to be about $2 billion annually, of which $1.7 billion is attributed to alpha blockers. Market leader Flomax - which had U.S. sales of about $1.5 billion in the last 12 months, according to IMS sales data - is expected to face generic competition in 2010.

An Oct. 9 analyst note by Cowen and Company estimates that Rapaflo will reach $40 million in sales in 2009, rising to $120 million in 2012.

- Jamie Hammon (j.hammon@elsevier.com)

Rapaflo Approved For BPH; Watson Will Stress Unique Selectivity

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