Patients with carcinoid syndrome, whose symptoms are not managed by octreotide therapy, are being recruited for a Phase 2 clinical trial of Lexicon Pharmaceuticals’ LX1606 (a.k.a. LX1032). The trial has been given Fast Track status in the U.S. and Orphan Drug designation in the European Union (EU). Studies are taking place in both the U.S. and in the EU (Germany).
In carcinoid syndrome, metastatic carcinoid tumors release excess serotonin and other substances into the blood stream. These are thought to cause a variety of symptoms including severe diarrhea, flushing, asthma-like wheezing, and rapid heartbeat. LX1606, an orally-delivered medication that acts by inhibiting the enzyme tryptophan hydoxylase (TPH), was designed to reduce serotonin production both inside and outside the GI tract without affecting brain serotonin levels. TPH is the rate-limiting enzyme involved in serotonin biosynthesis and is present in metastatic carcinoid tumor cells. Using research conducted in its Genome5000TM program, Lexicon scientists found that mice lacking the non-neuronal form of the TPH enzyme (TPH1) have virtually no peripheral serotonin, but do maintain normal levels of brain serotonin.
In Phase 1 clinical trials, LX1606 was tolerated at dose levels up to 1500 mg, and was well-tolerated over two weeks when given as 500 mg three times daily. In addition, a dose-dependent reduction in blood serotonin and urinary 5-HIAA levels (the primary metabolite of serotonin) was observed, confirming the compound’s mechanism of action. Learn more about the Phase 1 clinical results by watching Lexicon’s video presentation at http://www.lexpharma.com/lx1032-presentation.html.
In his introduction to the video, Dr. Arthur T. Sands, president and chief executive officer of Lexicon, notes, “LX1032 [LX1606] is now Lexicon’s third drug candidate to advance to Phase 2 clinical trials and we are very happy to see our new mechanisms translating now into opportunities to treat patients.”
According to Lexicon’s senior vice president of clinical development, Dr. Philip M. Brown, “Carcinoid syndrome truly represents an area of unmet medical need. We believe that LX1032 [LX1606] represents a novel approach to treating the symptoms associated with the condition.”
LX1606 has received Fast Track status from the FDA. The Fast Track program is designed to facilitate the development and expedite the review of new drugs intended to treat serious diseases, and which demonstrate the potential to address unmet medical needs. The purpose of the program is to get important new drugs to the patient earlier. Fast Track benefits include eligibility for an early review process that may significantly shorten FDA approval times. Carcinoid syndrome is the first therapeutic indication for which Lexicon has obtained Fast Track status.
In Europe, Orphan Drug designation promotes the development of drugs intended for the prevention or treatment of life-threatening or chronically debilitating conditions that affect no more than five in 10,000 people in the EU. LX1606 is the first drug candidate for which Lexicon has obtained Orphan Drug status.
In the United States, LX1606 is being evaluated in the following centers:
- M.D. Anderson Cancer Center, Houston, Texas
- Texas Oncology – McAllen, McAllen, Texas
- Hematology Oncology Services, Little Rock, Arkansas
- University of Iowa, Iowa City, Iowa
- Dana Farber Cancer Institute, Boston, Massachusetts
- Nebraska Methodist Hospital, Omaha, Nebraska
- Cedars-Sinai Medical Center, Los Angeles, California
- St. Francis Hospital & Health Center, Indianapolis, Indiana
In Europe, LX1606 is being evaluated in Germany at the following locations:
- Berlin, Germany
- Halle, Germany
- Marburg, Germany
- Munich, Germany
- Lübeck, Germany
For enrollment information about the ongoing LX1606 clinical trial in the U.S. for carcinoid syndrome, click here http://www.clinicaltrials.gov/ct2/show/NCT00853047?term=carcinoid+syndrome&rank=4.
Lexicon Pharmaceuticals (NASDAQ: LXRX) is a biopharmaceutical company focused on discovering breakthrough treatments for human disease. Lexicon currently has four drug candidates in mid-stage development for diabetes, irritable bowel syndrome, carcinoid syndrome and rheumatoid arthritis, all of which were discovered by Lexicon’s research team. Lexicon has used its proprietary gene knockout technology to identify more than 100 promising drug targets for small molecule drug discovery and development. For more information about the company please visit www.lexpharma.com.