First Presentation at a Scientific Meeting of Data from Companion Phase 3 Trial Designed to Assess Safety of Telotristat Ethyl for Carcinoid Syndrome
The Woodlands, Texas, October 3, 2016 – Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced that data from its TELECAST Phase 3 study were presented at the 2016 Annual Symposium of the North American Neuroendocrine Tumor Society (NANETS), held September 30 to October 1, 2016 in Jackson, Wyoming, by Dr. Marianne Pavel in a presentation, entitled “Efficacy and Safety Results of Telotristat Ethyl in Patients with Carcinoid Syndrome During the Double-blind Treatment Period of the TELECAST Phase 3 Clinical Trial.”
The Phase 3 TELECAST study was designed as a companion to Lexicon’s pivotal Phase 3 TELESTAR study primarily to provide additional safety exposure while further evaluating the activity of telotristat ethyl (previously referenced as telotristat etiprate, for telotristat ethyl hippurate) in carcinoid syndrome. TELECAST mostly enrolled patients treated with somatostatin analog (SSA) therapy, the current standard of care, with carcinoid syndrome characterized by less severe bowel movement frequency than those patients in TELESTAR (which required that patients have an average of at least four bowel movements a day to qualify for the study), but also enrolled a smaller number of carcinoid syndrome patients not treated with SSA therapy.
Safety and tolerability was one of the primary objectives of the TELECAST study, and telotristat ethyl was well tolerated during the double-blind treatment period. Across all three treatment arms (placebo, 250 mg, 500 mg, each taken three times daily), the incidence of treatment-emergent adverse events (AEs) were 80.8%, 100% and 84.0%, respectively; the incidence of serious AEs (SAEs) were 19.2%, 4.0% and 8.0%, respectively; and discontinuation due to AEs were 3.8%, 8.0% and 0%, respectively. AEs of depression or depressed mood were seen in two patients (7.7%) in the placebo arm and one (4.0%) in each of the telotristat ethyl treatment arms. Gastrointestinal AEs were seen in 57.7%, 64.0% and 36.0% of patients in the placebo, 250 mg and 500 mg treatment arms, respectively.
Telotristat ethyl met the study’s primary efficacy endpoint, the percent change from baseline in urinary 5-hydroxyindoleacetic acid (5-HIAA, the main metabolite of serotonin) at week 12, the final week of the double-blind treatment portion of the study (p<0.001 for both telotristat ethyl arms compared to placebo). The placebo-adjusted change in 5-HIAA was -54.0% and -89.7% for the 250 mg and 500 mg treatment arms, respectively.
In addition, despite the lower baseline bowel movement frequency than in TELESTAR, telotristat ethyl achieved statistically significant reductions in daily bowel movement frequency over the 12 weeks of the study (p=0.004 for the 250 mg treatment arm and p<0.001 for the 500 mg treatment arm compared to placebo). Baseline mean daily bowel movement frequency was 2.2, 2.5 and 2.8 in the placebo, 250 mg and 500 mg arms. Patients in the 250 mg and 500 mg dose arms experienced noteworthy reductions in daily bowel movement frequency early in the study that tended to increase over time. The placebo-adjusted reduction in daily bowel movement frequency over the entire 12-week period was -0.45 and -0.54 for the 250 mg and 500 mg treatment arms, respectively.
Notably, 40% of patients in each of the telotristat ethyl treatment arms achieved a ≥30% reduction in BM frequency for at least 50% of the days in the double-blind treatment period, while not a single patient in the placebo arm achieved that result (p=0.001 for both doses compared to placebo).
About Carcinoid Syndrome
Carcinoid syndrome is a rare disease affecting thousands of cancer patients with metastatic neuroendocrine tumors (mNETs) that have spread to the liver and other organs from the gastrointestinal tract. The condition is characterized by frequent and debilitating diarrhea that often prevents patients from leading active, predictable lives, as well as by facial flushing, abdominal pain, fatigue and, over time, heart valve damage.
About TELECAST and TELESTAR
The double-blind Phase 3 TELECAST study enrolled 76 patients with or without concomitant SSA therapy provided they qualified based on at least one sign/symptom of carcinoid syndrome, signs and symptoms of carcinoid syndrome, relating to either flushing, gastrointestinal symptoms, or elevated urinary 5-HIAA. The three-arm study evaluated two doses of oral telotristat ethyl – 250 mg and 500 mg, each taken three times daily – against placebo over a 12-week period with primary outcome measures consisting of safety and the percent change from baseline in urinary 5-HIAA, and secondary outcome measures including change from baseline in the number of daily bowel movements. Patients in both the treatment and placebo arms who were on SSA therapy at baseline continued their SSA therapy throughout the study.
Results from Lexicon’s pivotal Phase 3 TELESTAR study were presented in 2015 at the European Cancer Congress and the annual symposium of the North American Neuroendocrine Tumor Society.
About Telotristat Ethyl
Discovered using Lexicon’s unique approach to gene science, telotristat ethyl is the first investigational drug in clinical studies to target tryptophan hydroxylase, an enzyme that triggers the excess serotonin production within mNET cells that is a key driver of carcinoid syndrome. While existing treatments for carcinoid syndrome work to reduce the release of serotonin outside tumor cells, telotristat ethyl works at the source to reduce serotonin production within the tumor cells. By specifically inhibiting serotonin production, telotristat ethyl seeks to control this important driver of carcinoid syndrome and, in combination with SSA therapy, the current standard of care, to provide patients with more control over their disease.
Telotristat ethyl has received Fast Track and Orphan Drug designation from the U.S. Food and Drug Administration and has been granted priority review by the FDA with a Prescription Drug User Fee Act (PDUFA) target action date of February 28, 2017.
Lexicon retains rights to market telotristat ethyl in the U.S. and Japan, and is building the in-house commercial infrastructure to serve the U.S. market. Lexicon has a license and collaboration agreement with Ipsen to commercialize telotristat ethyl in Europe and other countries outside the U.S. and Japan.
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 ethyl (formerly referred to as telotristat etiprate and LX1032) and the results of and projected timing of clinical trials and the potential therapeutic and commercial potential of telotristat ethyl. 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 ethyl may be halted, delayed or otherwise not demonstrate safety or efficacy, the risk that the FDA and other regulatory authorities may not grant regulatory approval of telotristat ethyl 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 ethyl. As a result, telotristat ethyl 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, 2015, 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.