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News from the Industry

SURFACE LOGIX PHASE 1 CLINICAL TRIAL ACHIEVES TARGET PROFILE

SLx-2101, A Novel Long Acting PDE-5 Inhibitor for Disorders Related to Endothelial Dysfunction

The Phase I study was designed to assess the safety and tolerability of SLx-2101, establish the pharmacokinetic (PK) profile and to provide evidence of activity in two pharmacodynamic (PD) models.

In a double-blind, placebo controlled, randomized study, healthy male volunteers received single oral doses of SLx-2101 or placebo. Five dose levels were included and subjects were monitored for adverse events and pharmacokinetic sampling was performed out to 48 hours post dose. Two methods of assessing pharmacodynamic activity were included in the study. Erectile response was assessed over 24 hours using the Rigiscan^TM Plus system and peripheral arterial tone was assessed using the Endo-PAT2000^TM device.

The results from the trial confirm the ability of the Pharmacomer^TM Technology Platform to design specific pharmacokinetic performance into a molecule while optimizing potency and selectivity. The design of SLx-2101 and its preclinical program was directed to differentiate SLx-2101 from other PDE5 inhibitors based on the combined features of potency and duration of action in excess of 24 hours. The development plan for SLx-2101 includes a number of conditions related to endothelial dysfunction including male erectile dysfunction (MED), pulmonary arterial hypertension (PAH), and congestive heart failure (CHF).

SLx-2101 is an oral phosphodiesterase-5 (PDE-5) inhibitor designed using Surface Logix' proprietary small molecule Pharmacomer^TM Technology. SLx-2101 is being developed to treat endothelial dysfunction, a physiological disability of endothelial cells, the cells that line the inner surface of all blood vessels, arteries and veins, that prevents them from carrying out their normal biochemical functions. Normal endothelial cells are involved in mediating the processes of coagulation, platelet adhesion, immune function, control of volume and electrolyte content of the intravascular and extravascular spaces. Endothelial dysfunction is believed to be the underlying cause for several major diseases including atherosclerosis, congestive heart failure, hypertension and erectile dysfunction.

VIVUS Completes Enrollment in Phase 3 Study of Evamist(TM) for Treatment of Menopausal Symptoms

A pivotal Phase 3 clinical study of an investigational drug Evamist (TM) (Estradiol MDTS(R)), an estradiol spray for the treatment of vasomotor symptoms associated with menopause. This Phase 3 trial is a multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of Evamist. The primary endpoint is the reduction in the frequency and severity of moderate-to-severe vasomotor symptoms associated with menopause at weeks 4 and 12 of the study. Over 400 patients were enrolled at 43 centers throughout the United States. The study was initiated in December 2004 under a Special Protocol Assessment ("SPA") with the Food and Drug Administration ("FDA").

The SPA is a formal agreement that designates the agreed upon terms and conditions under which VIVUS will conduct and analyze the data from its Phase 3 trial. The SPA provides official confirmation from the FDA that the protocol design is sufficient for a Phase 3 trial which, if completed as agreed, can form the basis of the submission of a New Drug Application ("NDA") that will include an efficacy label claim for Evamist for the relief of moderate to severe vasomotor symptoms associated with menopause.

Evamist is an investigational drug that has not been approved by the FDA or any other regulatory authority. Evamist is a small, hand-held, easy-to-use spray that is designed to provide an easy and convenient means to deliver a preset dose of estradiol via the skin. The Evamist applicator is placed gently against the skin and an actuator button is pushed. A light spray containing a proprietary formulation of estradiol is then released, where it is absorbed into the dermal layer. This method of delivery eliminates the requirement to touch the formulation, and may decrease the transfer of the active ingredient to other areas of the body or to other persons. Estradiol is released into the blood stream on a sustained basis over 24 hours, providing a practical and convenient once-a-day dosing regimen. Evamist is believed to be the first transdermal estradiol spray delivery system under development in the United States. Evamist is fast drying, non-irritating and invisible after application.