Lexicon (LXRX) Up as Phase 2 Trial Of Telotristat Etiprate Shows Positive Results
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Shares of Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) are moving higher on Friday after the company announced positive, top-line data from a recently completed Phase 2 study in carcinoid syndrome with telotristat etiprate. Results from the trial will be presented at the North American Neuroendocrine Tumor Society on Saturday, October 13, 2012 in San Diego, California.
Carcinoid syndrome is a chronic condition caused by neuroendocrine tumors that usually originate from the gastrointestinal tract. It is characterized by severe diarrhea and flushing episodes with long-term consequences including malnutrition, heart disease, and death. Carcinoid syndrome has been linked to excess production of serotonin by metastatic tumor cells. Telotristat etiprate is an oral investigational new drug designed to treat carcinoid syndrome by reducing serotonin production in patients with metastatic carcinoid tumors. Telotristat etiprate has Fast Track status and Orphan Drug designation from the Food and Drug Administration, and Orphan Drug designation from the European Medicines Agency.
The primary efficacy endpoint of the trial was the reduction of bowel movements from baseline in patients with metastatic carcinoid syndrome who were refractory to or could not tolerate somatostatin analog therapy. Patients experienced a 46.4% median reduction from baseline at week 12, with the number of daily bowel movements steadily decreasing over time. All observed changes from baseline were statistically significant at p < 0.001. This change corresponded with an increased proportion of patients reporting adequate relief of their carcinoid symptoms, a global assessment which also improved over time, with 75% of the patients with data at week 12 reporting improvement. Clinically relevant decreases from baseline were likewise seen for a number of key secondary endpoints, including statistically significant improvements in stool consistency (p < 0.001) and trends of reductions in abdominal pain (p=0.09) and the number of cutaneous flushing episodes (p=0.052). The median percentage reductions from baseline of urinary 5-HIAA at weeks 8 and 12 were 68.3% (p=0.019) and 72.7% (p=0.031), respectively. Urinary 5-HIAA is a biomarker of serotonin synthesis and is of key interest in these patients.
"In this trial, telotristat etiprate provided rapid and durable benefit across several dimensions of carcinoid syndrome, a devastating metastatic cancer syndrome with few treatment options for patients," said Dr. Pablo Lapuerta, Lexicon's senior vice president and chief medical officer. "Of additional interest was improvement seen in two patients who were not on background somatostatin analog therapy, the only currently-approved treatment."
The open-label, dose-escalation study was conducted in Europe in 15 patients with metastatic carcinoid syndrome who were refractory to or could not tolerate somatostatin analog therapy. Efficacy measures included change in bowel movement frequency, relief of symptoms, and reduction in serotonin synthesis. Patients received ascending doses of 150 mg, 250 mg, 350 mg and 500 mg of telotristat etiprate, administered three times daily (TID), for 14 days on each dose until reaching a maximal dose, which was then continued until the completion of 12 weeks of therapy. Escalation to a higher dose was contingent on tolerability and clinical response. Fourteen patients (93%) completed the trial, and 12 of these 14 patients were treated with 500 mg TID of study drug during the last four weeks of the treatment period. The one patient who discontinued early withdrew from the 350mg TID dose level for reasons not related to drug safety. Notably, the two patients in the study who were not receiving background somatostatin analog therapy observed reductions in bowel movements of 67% and 48% from baseline to week 12.
Telotristat etiprate was well tolerated. There was no evidence of dose–limiting toxicity, and no patient discontinued from the study early due to an adverse event. Only three patients reported a serious adverse event, none of which was related to study drug.
"The positive results from this second Phase 2 trial of telotristat etiprate further support its potential utility in the treatment of carcinoid syndrome in a population that is refractory to or cannot tolerate current therapies," said Dr. Arthur T. Sands, Lexicon's president and chief executive officer. "Building upon results from our previously reported placebo-controlled four-week Phase 2 trial, this study showed strongly positive results in multiple parameters over twelve weeks of therapy, the same treatment period in our upcoming registrational, Phase 3 clinical trial."
Carcinoid syndrome is a chronic condition caused by neuroendocrine tumors that usually originate from the gastrointestinal tract. It is characterized by severe diarrhea and flushing episodes with long-term consequences including malnutrition, heart disease, and death. Carcinoid syndrome has been linked to excess production of serotonin by metastatic tumor cells. Telotristat etiprate is an oral investigational new drug designed to treat carcinoid syndrome by reducing serotonin production in patients with metastatic carcinoid tumors. Telotristat etiprate has Fast Track status and Orphan Drug designation from the Food and Drug Administration, and Orphan Drug designation from the European Medicines Agency.
The primary efficacy endpoint of the trial was the reduction of bowel movements from baseline in patients with metastatic carcinoid syndrome who were refractory to or could not tolerate somatostatin analog therapy. Patients experienced a 46.4% median reduction from baseline at week 12, with the number of daily bowel movements steadily decreasing over time. All observed changes from baseline were statistically significant at p < 0.001. This change corresponded with an increased proportion of patients reporting adequate relief of their carcinoid symptoms, a global assessment which also improved over time, with 75% of the patients with data at week 12 reporting improvement. Clinically relevant decreases from baseline were likewise seen for a number of key secondary endpoints, including statistically significant improvements in stool consistency (p < 0.001) and trends of reductions in abdominal pain (p=0.09) and the number of cutaneous flushing episodes (p=0.052). The median percentage reductions from baseline of urinary 5-HIAA at weeks 8 and 12 were 68.3% (p=0.019) and 72.7% (p=0.031), respectively. Urinary 5-HIAA is a biomarker of serotonin synthesis and is of key interest in these patients.
"In this trial, telotristat etiprate provided rapid and durable benefit across several dimensions of carcinoid syndrome, a devastating metastatic cancer syndrome with few treatment options for patients," said Dr. Pablo Lapuerta, Lexicon's senior vice president and chief medical officer. "Of additional interest was improvement seen in two patients who were not on background somatostatin analog therapy, the only currently-approved treatment."
The open-label, dose-escalation study was conducted in Europe in 15 patients with metastatic carcinoid syndrome who were refractory to or could not tolerate somatostatin analog therapy. Efficacy measures included change in bowel movement frequency, relief of symptoms, and reduction in serotonin synthesis. Patients received ascending doses of 150 mg, 250 mg, 350 mg and 500 mg of telotristat etiprate, administered three times daily (TID), for 14 days on each dose until reaching a maximal dose, which was then continued until the completion of 12 weeks of therapy. Escalation to a higher dose was contingent on tolerability and clinical response. Fourteen patients (93%) completed the trial, and 12 of these 14 patients were treated with 500 mg TID of study drug during the last four weeks of the treatment period. The one patient who discontinued early withdrew from the 350mg TID dose level for reasons not related to drug safety. Notably, the two patients in the study who were not receiving background somatostatin analog therapy observed reductions in bowel movements of 67% and 48% from baseline to week 12.
Telotristat etiprate was well tolerated. There was no evidence of dose–limiting toxicity, and no patient discontinued from the study early due to an adverse event. Only three patients reported a serious adverse event, none of which was related to study drug.
"The positive results from this second Phase 2 trial of telotristat etiprate further support its potential utility in the treatment of carcinoid syndrome in a population that is refractory to or cannot tolerate current therapies," said Dr. Arthur T. Sands, Lexicon's president and chief executive officer. "Building upon results from our previously reported placebo-controlled four-week Phase 2 trial, this study showed strongly positive results in multiple parameters over twelve weeks of therapy, the same treatment period in our upcoming registrational, Phase 3 clinical trial."
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