Lexicon's Telotristat Etiprate Shows Clinical Benefit In Treating Carcinoid Syndrome In Cancer Patients When Added To Standard Of Care

Pivotal TELESTAR Phase 3 Data Presented as Late-Breaking Oral Presentation at European Cancer Congress

Conference Call and Webcast on September 29, 2015 at 8:00 a.m. Eastern Time

Sep 29, 2015, 06:00 ET from Lexicon Pharmaceuticals, Inc.

THE WOODLANDS, Texas, Sept. 29, 2015 /PRNewswire/ -- Lexicon Pharmaceuticals, Inc.'s (Nasdaq: LXRX)  telotristat etiprate was shown to have clinical benefit in treating carcinoid syndrome in cancer patients not adequately controlled by long-acting somatostatin analog (SSA) therapy, the current standard of care, according to data from the Phase 3 TELESTAR study presented today at the European Cancer Congress in Vienna, Austria.

Telotristat etiprate, Lexicon's most advanced product candidate, met the study's primary endpoint with clinically meaningful reductions in bowel movement frequency in patients whose condition was not adequately controlled by SSA therapy. Carcinoid syndrome is characterized by frequent and debilitating diarrhea that often prevents patients from leading active, predictable lives, as well as by facial flushing, abdominal pain, heart valve damage and other serious consequences.

"We are pleased with the efficacy and safety results of telotristat etiprate and also with the durability of the response shown in this study," said Lexicon Executive Vice President and Chief Medical Officer Pablo Lapuerta, M.D. "The data also support that the compound is acting directly on the cause of carcinoid syndrome, by reducing serotonin production within tumor cells."

"Telotristat etiprate represents a novel approach by specifically inhibiting serotonin synthesis and, as such, is a promising potential new treatment for patients whose lives can be significantly impacted by this debilitating condition," said TELESTAR primary investigator Matthew H. Kulke, M.D., Director, Program in Neuroendocrine and Carcinoid Tumors and Senior Physician, Dana Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School. "These results are exciting from both an efficacy and safety perspective for carcinoid syndrome patients."  

Dr. Kulke's abstract, entitled "Telotristat etiprate is effective in treating patients with carcinoid syndrome that is inadequately controlled by somatostatin analog therapy (the Phase 3 TELESTAR clinical trial)" (37 LBA), was presented in a proffered paper session on gastrointestinal malignancies, Tuesday, September 29, at 10:30 a.m. CEST.

"Carcinoid syndrome has a significant impact on the lives of patients who already have been battling metastatic cancer," said Maryann Wahmann, Founder and President of the Neuroendocrine Cancer Awareness Network. "These patients can live for many years with their cancer, yet the symptoms of carcinoid syndrome are what frequently limit their lives and restrict their activities every single day. So there is a tremendous need for effective new treatment options."

TELESTAR Results

The double-blind Phase 3 study enrolled 135 patients with carcinoid syndrome that was not adequately controlled on SSA therapy. The three-arm study evaluated two doses of oral telotristat etiprate – 250 mg and 500 mg, each taken three times daily – against placebo over a 12-week period and measured the reduction from baseline in the average number of daily bowel movements. Patients in both the treatment and placebo arms continued their SSA therapy throughout the study.

Data show that patients who added telotristat etiprate to SSA therapy at both the 250 mg and 500 mg doses experienced a statistically significant reduction from baseline compared to placebo in the average number of daily bowel movements over the 12-week study period (p<0.001), meeting the study's primary endpoint.

Patients who received 250 mg of telotristat etiprate experienced a reduction of 1.71 bowel movements (29%) in the average number of daily bowel movements during the final week of the study compared to baseline, and those in the 500 mg arm experienced a reduction of 2.11 bowel movements (35%); the placebo group showed a reduction of 0.87 bowel movements (17%).

A substantially greater proportion of patients on telotristat etiprate achieved a durable response (44 percent and 42 percent in the 250 mg and 500 mg arms, respectively), defined as at least a 30 percent reduction in daily bowel movements over at least half the days of the study period, as compared to 20 percent response on placebo (p<=0.02).

The mean change in urinary 5-HIAA, the main metabolite of serotonin, from baseline to week 12 was a reduction of 40 mg/24 hours in the 250 mg arm and 58 mg/24 hours in the 500 mg arm versus an increase of 11 mg/24 hours in the placebo group (p<0.001).  Baseline urinary 5-HIAA levels were 93 mg/24 hours in the 250 mg arm, 90 mg/24 hours in the 500 mg arm, and 81 mg/24 hours in the placebo group.

Patients who received telotristat etiprate also experienced a lower frequency of flushing episodes and less intense abdominal pain compared to placebo, though these differences did not reach statistical significance. 

Treatment with telotristat etiprate was generally well tolerated during the double-blind treatment period.  The proportions of patients with treatment-emergent adverse events (AEs) were 82% in the 250 mg arm, 93% in the 500 mg arm and 87% in the placebo group during the 12-week study period.  The proportions of patients who discontinued treatment due to AEs in both the 250 mg and 500 mg arms were 7% as compared to 13% in the placebo group. 

The tolerability profile of the telotristat etiprate 250 mg dose appeared similar to placebo and somewhat better than the 500 mg dose in terms of gastrointestinal discomfort and mood. There were six events of patients experiencing mild to moderate nausea in the 250 mg arm, 13 in the 500 mg arm and five in the placebo group.  There were two events of depression or depressed mood in the 250 mg arm, eight in the 500 mg arm and three in the placebo group.  There were no discontinuations of treatment due to nausea, depression or depressed mood in the 250 mg and 500 mg arms during the 12-week study period.

Conference Call Information

Lexicon management will hold a conference call and webcast to discuss the TELESTAR Phase 3 results at 8:00 a.m. Eastern Time on September 29, 2015.  The dial-in number for the conference call is 888-645-5785 (within the US/Canada) or 970-300-1531 (international).  The conference ID for all callers is 49610409.  Investors can access a live webcast of the call at www.lexpharma.com.  An archived version of the webcast will be available on the website through October 29, 2015.

About Telotristat Etiprate

Discovered using Lexicon's unique approach to gene science, telotristat etiprate is the first investigational drug in clinical studies to target tryptophan hydroxylase, an enzyme that triggers the excess serotonin production within mNET cells that leads to carcinoid syndrome. While existing treatments for carcinoid syndrome work to reduce the release of serotonin outside tumor cells, telotristat etiprate works at the source to reduce serotonin production within the tumor cells. By specifically inhibiting serotonin production, telotristat etiprate seeks to control this important driver of carcinoid syndrome and, in turn, provide patients with more control over their disease.

Telotristat etiprate has received Fast Track and Orphan Drug designation from the U.S. Food and Drug Administration.

Lexicon retains rights to market telotristat etiprate in the U.S. and Japan, and is building the in-house commercial infrastructure to serve the U.S. market. The Company has a license and collaboration agreement with Ipsen to commercialize telotristat etiprate in Europe and other countries outside the U.S. and Japan.

About Carcinoid Syndrome

Carcinoid syndrome is a rare disease affecting thousands of patients with neuroendocrine tumors that originate in the gastrointestinal tract and metastasize or spread to the liver or other organs. Overproduction of serotonin within these metastatic neuroendocrine tumor (mNET) cells is a driver of carcinoid syndrome, which is characterized by debilitating diarrhea, facial flushing, abdominal pain, heart valve damage and other serious consequences. The severe and unpredictable diarrhea associated with carcinoid syndrome has a profound impact on cancer patients' lives, often preventing them from participating in daily activities.

The current standard of care for carcinoid syndrome is somatostatin analog depot injection (SSA), first approved in 1998. SSA therapy fails over time to maintain adequate control of carcinoid syndrome for most patients, with many becoming not adequately controlled within the first two years after the therapy is initiated. Patients with carcinoid syndrome can live for many years with metastatic cancer, requiring the need for long-term treatment options to effectively manage their disease.

About Lexicon

Lexicon is a fully integrated biopharmaceutical company that is applying a unique approach to gene science based on Nobel Prize-winning technology to discover and develop precise medicines for patients with serious, chronic conditions. Through its Genome5000™ program, Lexicon scientists have studied the role and function of nearly 5,000 genes over the last 20 years and have identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to safely and effectively treat disease. Lexicon has a pipeline of promising drug candidates in clinical and pre-clinical development in oncology, diabetes and metabolism. For additional information please visit www.lexpharma.com.

Safe Harbor Statement

This press release contains "forward-looking statements," including statements relating to Lexicon's clinical development of telotristat etiprate (LX1032) and the results of and projected timing of clinical trials and the potential therapeutic and commercial potential of telotristat etiprate.  In addition, this press release also contains forward-looking statements relating to Lexicon's growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information.  All forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including the risk that clinical studies of telotristat etiprate may be halted, delayed or otherwise not demonstrate safety or efficacy, the risk that Lexicon and its licensees may be unable to file for regulatory approval of telotristat etiprate with the FDA and other regulatory authorities in accordance with its currently anticipated timelines, the risk that the FDA and other regulatory authorities may not grant regulatory approval of telotristat etiprate in accordance with Lexicon's currently anticipated timelines or at all, and the risk that such regulatory approvals, if granted, may have significant limitations on the approved use of telotristat etiprate.  As a result, telotristat etiprate may never be successfully commercialized.  Other risks include Lexicon's ability to meet its capital requirements, successfully conduct preclinical and clinical development and obtain necessary regulatory approvals of its other potential drug candidates, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates.  Any of these risks, uncertainties and other factors may cause Lexicon's actual results to be materially different from any future results expressed or implied by such forward-looking statements.  Information identifying such important factors is contained under "Risk Factors" in Lexicon's annual report on Form 10-K for the year ended December 31, 2014, as filed with the Securities and Exchange Commission.  Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.

 

SOURCE Lexicon Pharmaceuticals, Inc.



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