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.
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SOURCE Lexicon Pharmaceuticals, Inc.