Skip to Content

Watson Announces Positive Data for RAPAFLO (silodosin), Its Investigational Product for BPH, at Regional AUA Conferences

- Results demonstrate the efficacy, safety and tolerability of RAPAFLO(TM) alone or in combination with treatments for erectile dysfunction -

CORONA, Calif., Sept. 29 /PRNewswire-FirstCall/ -- Watson Pharmaceuticals, Inc., a leading specialty pharmaceutical company, announced today that investigators presented efficacy and safety data on silodosin, its investigational treatment for benign prostatic hyperplasia (BPH, or prostate enlargement), at two regional meetings of the American Urological Association (AUA). The trade name for silodosin will be RAPAFLO(TM).

These abstracts included results of Phase 3 studies, which showed that treatment with RAPAFLO for up to one year effectively reduces the symptoms of BPH and is well tolerated without causing any significant changes in blood pressure or adverse cardiac effects. Cardiac safety data further demonstrated that RAPAFLO, used alone or in combination with medications for erectile dysfunction (ED), showed only minimal effects on blood pressure or heart rate.

"We are excited by these clinical data as they further support the strong and sustained efficacy, as well as the safety and tolerability of RAPAFLO that have been demonstrated in other trials," said Edward Heimers, Jr., Executive Vice President and President of Watson's Brand Division. "As a highly selective alpha-1A blocker, we believe that RAPAFLO will address an important medical need in urology. Earlier this year, the New Drug Application for RAPAFLO was filed, and we look forward to working with the U.S., Food and Drug Administration to make this treatment option available to patients."

Data at the New England Regional AUA

At this year's New England Regional meeting of the AUA, investigators presented two abstracts on the efficacy and safety of RAPAFLO.

The first abstract was a pooled analysis of two Phase 3 double-blind, placebo-controlled trials involving 923 generally healthy men ages 50 or older, with signs and symptoms of BPH, including a peak urine flow rate (Qmax) between 4 and 15 mL/sec (mean of 8.7 to 8.9) and International Prostate Symptom Score (IPSS) > or = 13 (mean of 21.3). Patients were randomized to either 8 mg RAPAFLO once daily (n=466) or placebo (n=457) for 12 weeks.

After 12 weeks of treatment, RAPAFLO significantly improved urinary symptoms, including IPSS (the primary endpoint), compared to placebo (mean reduction of -6.4 vs. -3.5, respectively; p<0.0001). On secondary measures, RAPAFLO improved Qmax scores both at 2 to 6 hours following the first dose (mean improvement of 2.8 mL/sec vs. 1.5 mL/sec for placebo; p<0.0001) and after 12 weeks (mean improvement of 2.6 vs. 1.5 for placebo; p=0.0007). In addition to reducing overall IPSS, RAPAFLO also improved IPSS subscores at 12 weeks, including irritative subscore (mean decline of -2.3 vs. -1.4 for placebo; p<0.0001), and obstructive subscore (mean decline of -4.0 vs. -2.1 for placebo; p<0.0001).

Over the course of 12 weeks, treatment was well tolerated and the effect on blood pressure was similar between the RAPAFLO and placebo groups. Incidences of treatment-related dizziness and headache were low. Adverse events were minimal and were generally mild and related to retrograde ejaculation (reduced semen). There were no treatment-related cardiac events or hypertension.

The second abstract included data from a 9-month, open-label extension trial involving patients who had successfully completed the two previous 12-week, Phase 3 trials. A total of 661 patients were enrolled to receive RAPAFLO 8 mg once daily for an additional 40 weeks; 435 (65.8%) completed the extension study. A safety evaluation was based on adverse events, vital signs and clinical laboratory tests, electrocardiography (ECG), and physical examinations. An efficacy endpoint was change in IPSS at 40 weeks.

All 661 patients were included in the safety evaluation. Over the course of one-year of treatment, RAPAFLO was shown to be safe and well tolerated. Sixty-five percent (65.2%) of all patients reported at least one adverse event; less than one third of these (28.4%) were drug related. There were no serious drug-related adverse events. RAPAFLO was not associated with any clinically meaningful changes in blood pressure, clinical laboratory parameters, ECG results, or physical examination findings. Retrograde ejaculation (reduced semen) was the most common adverse event, though it rarely leads to drug discontinuation.

In the evaluable population of 429 (64.9%) patients, the IPSS decreased by a mean of 3.1 points between weeks 0 and 40. Although the change was larger (mean .4.4 points) in patients previously given placebo, the total score also decreased (mean .1.6 points) in patients previously treated with RAPAFLO. Treatment with RAPAFLO for up to one year also reduced IPSS irritative subscore (-1.7 points in patients previously on placebo and -0.6 in patients continuing RAPAFLO) and obstructive subscore (-2.7 in patients previously on placebo and -1.0 in patients continuing RAPAFLO).

Data at the Mid Atlantic Regional AUA

A placebo-controlled, open-label, crossover trial, presented at the Mid Atlantic Regional meeting, evaluated the concomitant use of RAPAFLO with the maximum doses of sildenafil or tadalafil, two agents commonly used to treat ED.

In the study, 22 healthy men (ages 45 to 78 years) received 8 mg RAPAFLO once daily for 21 days. On days 7, 14, and 21, subjects randomly received a single dose of 100 mg sildenafil, 20 mg tadalafil, or placebo. Resting (baseline) and standing orthostatic measurements were performed 0h (predose) to 12h after single-dose treatment. A positive orthostatic test was defined as a decrease in systolic (or diastolic) blood pressure by >30 (or >20) mm Hg, increased heart rate (>20 bpm), or orthostatic symptoms on change of position, such as dizziness.

Overall, concomitant use of RAPAFLO and maximum doses of sildenafil or tadalafil in healthy men caused no symptomatic changes in blood pressure, heart rate, or orthostatic symptoms. The cumulative number of positive orthostatic tests was similar for all treatments -- in 16 subjects <65 years (sildenafil, 28; tadalafil, 27; placebo 29) and in six subjects> or = 65 years (sildenafil, 6; tadalafil, 8; placebo 5).

"These data provide important new evidence about this potential treatment option for BPH. Considering that many men with BPH also have other co-morbid conditions, including erectile dysfunction, heart failure, hypertension and coronary artery disease, it's important to find complementary treatments that can be used with other medications without deleterious cardiovascular interactions, including the prolongation of the QTc interval and do not complicate patient care," said Norman Lepor, M.D., a cardiologist and associate clinical professor of medicine, University of California, Los Angeles (UCLA) and attending cardiologist at the Heart Institute at Cedars-Sinai Medical Center.

About RAPAFLO(TM) (silodosin)

RAPAFLO is a highly selective alpha-1 adrenergic receptor antagonist under development in the US for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). RAPAFLO binds with high affinity to the alpha (1A) receptors in the prostate causing the smooth muscles in these tissues to relax, resulting in an improvement in urine flow and a reduction in BPH symptoms. The binding affinity for the alpha (1B) receptors that cause smooth muscle relaxation and blood pressure effects in the cardiovascular system is significantly lower, thereby maximizing target organ activity for treating BPH while minimizing the potential for blood pressure effects. RAPAFLO was originally developed by Kissei Pharmaceutical Co., Ltd. in Japan and licensed to Watson for the US, Canada and Mexico markets.

About Watson Pharmaceuticals, Inc.

Watson Pharmaceuticals, Inc., headquartered in Corona, CA, is a leading specialty pharmaceutical company that develops, manufactures, markets, sells and distributes brand and generic pharmaceutical products. Watson pursues a growth strategy combining internal product development, strategic alliances and collaborations and synergistic acquisitions of products and businesses.

The mission of Watson Urology is to offer products and services that improve the quality of patients' lives, and satisfy the needs of physicians who specialize in the diagnosis, management, and treatment of urological disorders. By advancing education and support for urological diseases, we are creating the differences that make life more livable.

In the U.S., the Watson portfolio includes: Oxytrol(R); TRELSTAR(R) LA; TRELSTAR(R) Depot; Androderm(R); ProQuin(R) XR, under a co-promotion agreement with Depomed, Inc.; and AndroGel(R), under a co-promotion agreement with Solvay Pharmaceuticals, Inc. The Watson portfolio also includes a number of products under development including: silodosin, a product under development for the treatment of benign prostatic hyperplasia; a six-month formulation of TRELSTAR(R) (triptorelin pamoate for injectable suspension), under development for the treatment of advanced prostate cancer; and OTG, under development for overactive bladder.

Forward-Looking Statement

Any statements contained in this press release that refer to future events or other non-historical facts are forward-looking statements that reflect Watson's current perspective of existing trends and information as of the date of this release. Except as expressly required by law, Watson disclaims any intent or obligation to update these forward-looking statements. Actual results may differ materially from Watson's current expectations depending upon a number of factors affecting Watson's business. These factors include, among others, the difficulty of predicting the timing or outcome of product development efforts and FDA or other regulatory agency approvals or actions, if any; whether the results of clinical trials for silodosin and other information will be sufficient to support approval by FDA or other regulatory authorities; the impact of competitive products and pricing; market acceptance of and continued demand for Watson's products, including silodosin; difficulties or delays in manufacturing; and other risks and uncertainties detailed in Watson's periodic public filings with the Securities and Exchange Commission, including but not limited to Watson's Annual Report on Form 10-K for the year ended December 31, 2007.

Source: Watson Pharmaceuticals, Inc.

CONTACT: Patty Eisenhaur of Watson Pharmaceuticals, Inc.,
+1-951-493-56;sup id="bwanpa17">TM study (Fluocinolone Acetonide in Diabetic Macular Edema), is designed primarily to assess systemic exposure of the corticosteroid, fluocinolone acetonide (FA) after administration of Iluvien in diabetic macular edema (DME) patients. The study is also designed to provide information on the safety and efficacy of Iluvien in a DME population.

A total of 37 subjects were enrolled in the PK study, 20 patients received a low-dose Iluvien (which delivers an approximate 0.23µg per day dose) and 17 patients received a higher-dose Iluvien (which delivers an approximate 0.45µg per day dose).

The six-month interim readout from the PK study showed 25% of the low dose patients and 41% of the higher dose patients had an improvement in best corrected visual acuity (BCVA) of 10 or more letters on an eyechart compared with their baseline vision. In addition, the six-month readout showed 18% of the higher dose patients had an improvement in BCVA of 15 or more letters from baseline. The percentage of low dose patients that had an improvement in BCVA of 15 or more letters from baseline decreased from the 20% seen at the three-month readout due to one patient having developed a cataract and one patient having developed an epiretinal membrane involving the macula prior to the readout. The development of cataracts and epiretinal membranes in a diabetic population are not unusual and are commonly addressed with surgical intervention.

At three months, 29% of higher dose patients and 20% of low dose patients had gained 10 or more letters in BCVA compared to baseline. 18% of the higher dose and 20% of the low dose patients had gained 15 or more letters.

From a safety perspective, 12% of patients in the higher dose group and no patients in the low dose had a recorded intraocular pressure (IOP) of above 30mmHg during the six months. This was unchanged from the three month read-out. At six months, two patients in each group had experienced an adverse event related to cataract formation and one additional patient in each group underwent cataract extraction.

Iluvien is an intravitreal insert (formerly known as Medidur) being developed for the treatment of DME, a disease of the retina that affects individuals with diabetes. DME is one of the leading causes of blindness in people under 65 years of age. Each Iluvien insert is designed to provide a sustained therapeutic effect, up to 24 months for the low dose and up to 36 months for the higher dose. Iluvien is inserted into the patients eye with a 25-gauge injector system, which allows for a self-sealing wound. This insertion is very similar to an intravitreal injection, a procedure commonly employed by retinal specialists.

The early readout from this PK study and comparison with Bausch & Lombs Retisert® (also developed by pSivida) provides further insight into the dose-response of Iluvien. Retisert releases the same drug, FA, as Iluvien but at a higher dose and faster release rate (initially 0.6 µg per day). In a similarly sized clinical trial of Retisert in DME at 6 months, 27% of patients receiving Retisert had gained 10 or more letters of BCVA and 15% gained more than 15 lettersii. Iluvien was designed with the hypothesis that by better device design it would be possible to achieve similar efficacy in DME to Retisert, while reducing side effects and improving ease of administration.

This very encouraging six-month readout from the Iluvien PK study indicates continued improvement of visual acuity and continues to support the hypothesis that Iluvien, can have a substantial impact on DME while minimizing the side effects usually associated with corticosteroids, said Dr. Paul Ashton, Managing Director, pSivida Corp.

Data from the PK study is being evaluated on an ongoing basis with interim looks at months 3,6,12 18, 24 and 36. Except for the month 12 and final month 36 looks, when the database will be fully locked, interim evaluations are based on unaudited data. The last patient was enrolled in this study at the end of February 2008.

i The study of absorption, distribution, metabolism and excretion of a drug.

ii Data presented at the American Academy of Ophthalmology in 2002

About pSivida Corp.

pSivida is a drug delivery company committed to the biomedical sector, with a primary focus on ophthalmology and oncology. pSivida has two products approved by the Food and Drug Administration (FDA): Retisert® for the treatment of uveitis and Vitrasert® for the treatment of AIDS-related cytomegalovirus (CMV) retinitis. pSivida has licensed both of these products and the technologies underlying them to Bausch & Lomb Incorporated. pSivida has one product in fully recruited Phase III clinical trials: Iluvien, which delivers fluocinolone acetonide (FA) for the treatment of diabetic macular edema (DME), formerly known as Medidur FA for DME. pSivida has licensed certain drug delivery technology to Alimera Sciences, Inc. for the development of Iluvien and certain other ophthalmic products. pSivida has a worldwide collaborative research and license agreement with Pfizer Inc. under which Pfizer may develop additional ophthalmic products..

pSivida owns the rights to develop and commercialize a modified form of silicon known as BioSilicon, which has potential therapeutic applications. The most advanced BioSilicon product candidate, BrachySil, delivers a therapeutic P32, a radioactive form of phosphorus used to treat cancer, directly to solid tumors. pSivida recently completed a initial safety and efficacy clinical trial of BrachySil for the treatment of pancreatic cancer and has commenced a dose-ranging clinical trial.

pSividas intellectual property portfolio consists of 64 patent families, 122 granted patents, including patents accepted for issuance, and 282 patent applications. pSivida conducts its operations from Boston in the United States, and Malvern in the United Kingdom .

SAFE HARBOR STATEMENTS UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995: Various statements made in this release are forward-looking and involve a number of risks and uncertainties. All statements that address activities, events or developments that we intend, expect or believe may occur in the future are forward-looking statements. The following are some of the factors that could cause actual results to differ materially from the forward-looking statements: inability to raise capital; continued losses and lack of profitability; inability to derive revenue from Retisert; termination of license agreements; inability to pay any registration penalties; inability to develop or obtain regulatory approval for new products; inability to protect intellectual property or infringement of others intellectual property; inability to obtain partners to develop and market products; competition; risks and costs of international business operations; manufacturing problems; insufficient third-party reimbursement for products; failure to retain key personnel; product liability; failure to comply with laws; failure to achieve and maintain effective internal control over financial reporting; impairment of intangibles; volatility of stock price; possible dilution through exercise of outstanding warrants and stock options or future stock issuances; possible influence by Pfizer; and other factors that may be described in our filings with the Securities and Exchange Commission. Given these uncertainties, readers are cautioned not to place undue reliance on such forward-looking statements. We do not undertake to publicly update or revise our forward-looking statements even if experience or future changes make it clear that any projected results expressed or implied in such statements will not be realized.

Sivida Corp.

Posted: October 2008