Ligand Announces Favorable Results From Phase 1b Trial With LGD-6972 in Type 2 Diabetes and Plans to Initiate a Phase 2 Trial
Presentation at the American Diabetes Association 75th
Scientific Sessions
SAN DIEGO--
Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) announces
results from a Phase 1b clinical trial with LGD-6972 that demonstrate
favorable safety, tolerability and pharmacokinetics in normal healthy
volunteers and in subjects with type 2 diabetes mellitus. The trial
results also demonstrate a robust, dose-dependent reduction of fasting
plasma glucose. LGD-6972 is Ligand’s novel glucagon receptor antagonist,
and these results were presented at the American Diabetes Association’s
75th Scientific Sessions meeting underway in Boston.
Glucagon receptor antagonists are the leading non-insulin mechanism in
development for the treatment of type 2 diabetes. Based on earlier data
and these latest results, Ligand believes LGD-6972 has best-in-class
properties given its potency, preliminary effectiveness in lowering
plasma glucose in patients with type 2 diabetes and its safety profile
demonstrated in two Ligand-sponsored clinical trials.
In this randomized, double-blind, placebo-controlled trial, LGD-6972 was
administered in sequential increasing oral doses daily over two weeks to
both healthy subjects and subjects with type 2 diabetes. A total of 48
subjects were enrolled in the trial.
Highlights of the study include:
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LGD-6972 tested at 5mg, 10mg and 15mg was safe and well-tolerated with
no clinically significant or dose-dependent changes in hematology,
clinical chemistry or urinalysis panels, ECG or vital signs. There
were no serious adverse events and no study discontinuations. All
treatment-emergent adverse events were of mild or moderate severity
(grade 1 or 2).
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Plasma levels increased linearly with LGD-6972 dosage, and the
pharmacokinetic profiles were comparable between normal and type 2
diabetes subjects, supporting once-daily dosing.
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LGD-6972 lowered fasting plasma glucose in normal subjects and in
subjects with type 2 diabetes. Glucose was reduced throughout the
14-day dosing period. Baseline adjusted glucose values showed
dose-dependent effects of LGD-6972 in type 2 diabetic subjects with a
maximal decrease of 60 mg/dL.
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7 point glucose measurements were performed at baseline and Day 14 and
illustrated that LGD-6972 decreased glucose throughout a 24-hour
period in both fasting and post-prandial states.
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LGD-6972 is a highly potent and selective glucagon receptor antagonist
and is a promising agent for the treatment of type 2 diabetes.
Ligand is preparing to initiate a Phase 2 trial with LGD-6972 in 2016
with the goal to establish additional safety and efficacy for the
program in 12 consecutive weeks of dosing in subjects with type 2
diabetes. Approximately 100 subjects will be enrolled in this
randomized, double-blind, multicenter trial. The trial is estimated to
cost approximately $10 million and should be completed in 2017. Any
incremental increase to Ligand’s annual R&D spending as a result of this
program is expected to be covered within Ligand’s financial operations,
and there is no change to the company’s long-term earnings guidance.
“We are very pleased with these most recent findings with LGD-6972 which
build upon the Phase 1 single-ascending dose trial results we reported
at last year’s ADA meeting. We believe we are at the right place at the
right time as given what we know about LGD-6972 and the programs
underway at Eli Lilly and Pfizer, we may have the best-in-class
molecule. Moreover, glucagon antagonism has emerged over the past few
years as the leading non-insulin mechanism for type 2 diabetes in
development,” said John L. Higgins, Chief Executive Officer.
“We have the team, the capital and the financial strength to advance
this program, and believe continued internal development of LGD-6972 is
in the best interests of Ligand’s shareholders,” he added. “Against the
backdrop of the largest product portfolio ever, promising late-stage
partnered assets and an increasingly profitable business, we are excited
to be advancing a potentially major novel molecule for a very large
therapeutic opportunity.”
About Ligand’s Glucagon Receptor Antagonist Program
Glucagon is a hormone produced by the pancreas that stimulates the liver
to produce glucose (sugar). Overproduction of glucose by the liver is an
important cause of high glucose levels in patients with type 2 diabetes
and is believed to be due in part to inappropriately elevated levels of
glucagon. Glucagon receptor antagonists are designed to lower glucose
levels by reducing the production of glucose by the liver. Glucagon
receptor antagonists are novel molecules that have demonstrated a
reduction of glucose and hemoglobin A1c (HbA1c) in mid-stage clinical
trials.
LGD-6972 has been studied in previously-published preclinical and
clinical studies. Presentations from preclinical studies have shown that
LGD-6972 is highly potent and selective and inhibits glucagon-induced
hyperglycemia in both rats and monkeys, and that it also significantly
lowers glucose in a mouse model of type 2 diabetes. Additionally,
LGD-6972 significantly lowered fasting and non-fasting glucose levels in
a mouse model of type 1 diabetes and also reduced HbA1c, ketone bodies
and free fatty acids. LGD-6972 also has been shown to have additive
effects when used in combination with insulin therapy and may also be
useful in an insulin-sparing regimen. In a previous Phase 1a
single-ascending dose clinical study, LGD-6972 was well-tolerated, with
no clinically significant or dose-dependent changes in hematology,
clinical chemistry or urinalysis panels, ECG or vital signs, and no
serious adverse events. After a single dose, LGD-6972 reduced fasting
plasma glucose in normal healthy volunteers and in subjects with type 2
diabetes; fasting plasma glucose was reduced by 57 mg/dL
(placebo-adjusted) in subjects with type 2 diabetes.
About Diabetes
Diabetes is a growing global epidemic that currently affects more than
387 million people worldwide. In the United States, approximately 29
million people have diabetes, or roughly 9% of the total population. If
current trends continue, by 2050 fully 33% of the U.S. population will
be affected. People with type 2 diabetes either are resistant to the
effects of insulin or do not produce enough insulin to maintain a normal
glucose level. Sustained high glucose levels can cause diabetic
complications such as heart disease, stroke, kidney failure, neuropathy,
lower-limb amputations and blindness. Although type 2 diabetes is more
common in adults, it increasingly affects children as childhood obesity
increases. An estimated 90% to 95% of Americans with diabetes have type
2 diabetes.
The market for diabetes drugs is expected to nearly double to $68
billion by 2022 as treatment paradigms shift toward combination
therapies and novel non-insulin drugs. The top 10 non-insulin diabetes
drugs had total sales of $12 billion in 2014, and sales are expected to
increase to $20 billion by 2020.
About Ligand Pharmaceuticals
Ligand is a biopharmaceutical company with a business model focused on
developing or acquiring royalty generating assets and coupling them with
a lean corporate cost structure. Ligand’s goal is to produce a bottom
line that supports a sustainably profitable business. By diversifying
the portfolio of assets across numerous technology types, therapeutic
areas, drug targets and industry partners, we offer investors an
opportunity to invest in the increasingly complicated and unpredictable
pharmaceutical industry. In comparison to its peers, we believe Ligand
has assembled one of the largest and most diversified asset portfolios
in the industry with the potential to generate revenue in the future.
These therapies seek to address the unmet medical needs of patients for
a broad spectrum of diseases including diabetes, hepatitis, muscle
wasting, Alzheimer’s disease, dyslipidemia, anemia, asthma and
osteoporosis. Ligand’s Captisol® platform technology is a
patent-protected, chemically modified cyclodextrin with a structure
designed to optimize the solubility and stability of drugs. Ligand has
established multiple alliances with the world's leading pharmaceutical
companies including; Novartis, Amgen, Merck, Pfizer, Baxter
International and Eli Lilly.
Forward-Looking Statements
This news release contains forward-looking statements by Ligand that
involve risks and uncertainties and reflect Ligand's judgment as of the
date of this release. These forward-looking statements include comments
regarding the costs and timing of future clinical trials, the ability of
Ligand to enroll patients in a new clinical trial, the expectation that
the results from completed clinical trials predict the results of future
clinical trials, the ability of Ligand’s cash flow from operations to
cover the costs of a Phase 2 clinical trial, the impact of clinical
trials on Ligand’s financial guidance, the expected positive return to
investors, as well as the growth of the population with diabetes and the
trends in the market to treat diabetes. The failure to meet expectations
with respect to any of the foregoing matters may reduce Ligand's stock
price. Additional information concerning these and other important risk
factors affecting Ligand (including Ligand’s current reliance on
revenues based on sales of Promacta® and Kyprolis®, and various risks to
which Ligand’s Captisol® cyclodextrin operations are subject) can be
found in Ligand's prior press releases available at www.ligand.com
as well as in Ligand's public periodic filings with the Securities and
Exchange Commission, available at www.sec.gov.
Ligand disclaims any intent or obligation to update these
forward-looking statements beyond the date of this press release, except
as required by law. This caution is made under the safe harbor
provisions of the Private Securities Litigation Reform Act of 1995.
View source version on businesswire.com: http://www.businesswire.com/news/home/20150607005055/en/
Ligand Pharmaceuticals Incorporated
Todd Pettingill, 858-550-7500
investors@ligand.com
or
LHA
Bruce
Voss, 310-691-7100
bvoss@lhai.com
Source: Ligand Pharmaceuticals Incorporated
Released June 7, 2015