Drug Pipeline Series: Phase III ---Oct16-Oct23, 2006

AMITIZA™ (lubiprostone) Phase III Constipation Trial Results Demonstrate Improvements in Symptoms of Irritable Bowel Syndrome with Constipation
In recent studies, AMITIZA™ (lubiprostone) demonstrated improvements in relief of symptoms associated with irritable bowel syndrome with constipation (IBS-C), such as abdominal bloating and discomfort. Results of sub-analyses from two Phase III chronic constipation studies of AMITIZA, the first selective chloride channel activator approved by the FDA for the treatment of chronic idiopathic constipation in adults, were presented at the 71st American College of Gastroenterology (ACG) Annual Scientific Meeting.
According to the ACG, as many as 58 million Americans suffer from irritable bowel syndrome (IBS), a condition that accounts for as much as 50 percent of referrals to gastroenterologists each year, and includes IBS-C.
AMITIZA has a novel mechanism of action that works by activating chloride channels to increase fluid secretion in the intestine, thereby increasing the passage of stool and improving signs and symptoms associated with chronic idiopathic constipation. AMITIZA is the only prescription medication for chronic idiopathic constipation that has been approved by the FDA for use in adults, including those 65 years and over and that has demonstrated effectiveness for use beyond 12 weeks.
To evaluate efficacy and symptom improvements in chronic constipation patients treated with AMITIZA with a history of IBS-C, pooled results from two Phase III chronic idiopathic constipation trials were examined. To create an adequate group of IBS-C patients, data from two placebo-controlled clinical trials of 4 weeks were examined together. The pooled IBS-C subgroup consisted of 91 patients: 45 participants received placebo and 46 participants received AMITIZA 24 mcg taken twice daily.

Lilly Launches Phase III 'GALES' Trial of ALIMTA® (Pemetrexed for Injection) in Small Cell Lung Cancer
Eli Lilly and Company has launched a major clinical trial evaluating ALIMTA (pemetrexed for injection) in extensive-stage small cell lung cancer (SCLC), a devastating and rapidly spreading form of lung cancer. This international trial, expected to be the largest ever to be conducted in SCLC(1), will assess the potential clinical benefit of pemetrexed in combination with carboplatin, a commonly-used chemotherapeutic agent, in direct comparison to the current leading treatment option of etoposide in combination with carboplatin.
The trial -- known as GALES for Global Analysis of Pemetrexed in SCLC Extensive Stage -- is a Phase III, global, multicenter, randomized, open-label study that will enroll approximately 1,820 patients with extensive-stage SCLC. The study's primary objective is to compare the overall survival after treatment with pemetrexed plus carboplatin versus etoposide plus carboplatin in previously untreated patients with extensive-stage SCLC. The principal investigator of this study is Nick Thatcher, M.D. of Christie Hospital NHS Trust in Manchester, United Kingdom.
SCLC accounts for between 15 and 20 percent of all lung cancers.(2) Although SCLC is less common than the other main category of lung cancer -- non-small cell lung cancer, SCLC tends to spread more quickly and, as a result, people are typically diagnosed with extensive disease and left without options such as surgery to remove the cancer.

Somaxon Pharmaceuticals' SILENOR™ Demonstrates Positive Results in a Phase 3 Transient Insomnia Clinical Trial
Somaxon Pharmaceuticals, Inc. announced positive results from the company's Phase 3 clinical trial evaluating SILENOR™ (doxepin HCl) in adults with transient insomnia. SILENOR™ demonstrated statistically significant improvements compared to placebo (p<0.0001) in the primary endpoint of this trial, Latency to Persistent Sleep (LPS), a measure of sleep onset. SILENOR™ also produced statistically significant improvements relative to placebo in multiple secondary endpoints, including measures of both sleep onset and sleep maintenance.
This Phase 3 trial was a randomized, double-blind, placebo-controlled, multi-center, parallel group study that enrolled 565 adults in a sleep laboratory setting using a phase-advance, first night assessment model of induced transient insomnia. Efficacy assessments evaluated both objective PSG (polysomnography) and subjective measures of sleep. Results demonstrated that 6mg of SILENOR™ was effective at inducing sleep and maintaining sleep throughout the night.
SILENOR™ achieved statistically significant results in multiple endpoints including:
* Latency to Persistent Sleep (LPS): Improvement compared with placebo of 13 minutes (p<0.0001) * Latency to Sleep Onset (LSO), a subjective measure: Improvement compared with placebo of 16 minutes (p<0.0001) * Wake After Sleep Onset (WASO): Improvement compared with placebo of 40 minutes (p<0.0001) * Total Sleep Time (TST): Improvement compared with placebo of 51 minutes (p<0.0001)

NEUROGESX REPORTS RESULTS OF POST-HERPETIC NEURALGIA STUDY
NeurogesX has announced positive results from a multicenter, double-blind, controlled Phase III trial of Transacin (NGX-4010), the company's high-concentration trans-capsaicin dermal patch, in patients with post-herpetic neuralgia (PHN). The study met its prespecified primary endpoint with patients reporting statistically significant pain reduction after a single one-hour application of Transacin. A significant reduction in pain was noted during the first week following treatment and was maintained throughout the 12-week study period. At 12 weeks, more than one-half of all subjects treated with Transacin reported improvement in their condition, as measured by the Patient Global Impression of Change scale.
The study was conducted at 53 clinical sites in the U.S. A total of 402 patients suffering from PHN were randomized to a single, one-hour treatment with Transacin or to a matching, low-concentration capsaicin control patch. Study subjects were then followed for 12 weeks. Pain was recorded daily by study subjects using the Numeric Pain Rating Scale of zero (no pain) to 10 (worst possible pain).
Transacin is a topical, physician-administered patch containing a high concentration of trans-capsaicin, a synthetic form of the naturally occurring TRPV1 agonist capsaicin. Unlike current treatment approaches for neuropathic pain that include opioids and other agents - which act on the central nervous system and can cause drowsiness or other systemic side effects - the patch is designed to act peripherally in the skin, where the pain frequently originates. The incidence for safety issues or side effects that negatively impact quality of life is expected to be low.