Lexicon Pharmaceuticals, Inc. (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.”
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. (Original Source)
Shares of Lexicon Pharmaceuticals yesterday at $10.90. LXRX has a 1-year high of $15.79 and a 1-year low of $5.60. The stock’s 50-day moving average is $12.14 and its 200-day moving average is $8.96.
On the ratings front, Lexicon has been the subject of a number of recent research reports. In a report released yesterday, Wedbush analyst Liana Moussatos reiterated a Buy rating on LXRX, with a price target of $19, which represents a potential upside of 74.3% from where the stock is currently trading. Separately, on August 10, J.P. Morgan’s Jessica Fye downgraded the stock to Hold and has a price target of $14.
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Liana Moussatos and Jessica Fye have a total average return of 10.8% and -30.4% respectively. Moussatos has a success rate of 35.0% and is ranked #277 out of 3752 analysts, while Fye has a success rate of 0.0% and is ranked #3577.
Lexicon Pharmaceuticals Inc operates as a biopharmaceutical company engaged in discovery and development of breakthrough treatments for human disease.