Ligand Presents Positive Results from Phase 1 Clinical Trial of Captisol-enabled Iohexol
November 08 2019 - 8:30AM
Business Wire
Presentation at the American Society of
Nephrology (ASN) Kidney Week 2019
Ligand Pharmaceuticals Incorporated (NASDAQ: LGND)
presented positive results today from a Phase 1 clinical trial of
its Captisol-enabled (CE) Iohexol program at ASN Kidney Week 2019
in Washington, D.C. The CE-Iohexol program was established in
January 2018 to develop a Captisol-enabled, next-generation
contrast agent for diagnostic imaging with a reduced risk of renal
toxicity. The trial achieved the primary endpoint demonstrating
pharmacokinetic bioequivalence between CE-Iohexol injection and a
reference Iohexol injection (OMNIPAQUE™) after intravenous (IV)
administration in healthy adults. CE-Iohexol injection was safe and
well tolerated, and adverse events were in line with the known
safety profile of OMNIPAQUE.
Contrast agents are used to enhance diagnostic imaging. Despite
their benefits and widespread use, contrast agents may place
patients at an increased risk for acute kidney injury (AKI),
especially those with certain risk factors undergoing cardiac
interventional procedures utilizing intravascular iodinated
contrast.1 CE-Iohexol is designed to reduce the risk of AKI during
imaging procedures where iodinated contrast agents are
administered. In preclinical studies using an animal model of AKI,
CE-Iohexol administered at a dose similar to the clinical usage of
iohexol in humans significantly reduced renal injury compared to
iohexol alone and increased survival from 50% to 88%.2
The goal of the Phase 1 trial was to establish pharmacokinetic
bioequivalence to support subsequent clinical trials that could
support the submission of a 505(b)(2) new drug application (NDA) to
the U.S. Food and Drug Administration (FDA). The trial design
consisted of a single-center, randomized, double-blind, two-period
crossover study to determine relative bioavailability of CE-Iohexol
and a reference Iohexol injection (OMNIPAQUE) after IV
administration in a population of 24 healthy adults
(NCT03869983).
Highlights of the data presented today include:
- In two treatment periods, subjects received each treatment as a
single IV dose of 80 milliliters (mL) infused over approximately 20
seconds by a power injector: CE-Iohexol, 755 mg/mL iohexol (350 mg
I/mL)/50 mg CAPTISOL®/mL; OMNIPAQUE, 755 mg/mL iohexol (350 mg
I/mL).
- Bioequivalence between CE-Iohexol and OMNIPAQUE was
demonstrated for the key pharmacokinetic (PK) parameters of area
under the concentration-time curve (AUC) and maximum concentration
(Cmax).
- Geometric mean ratio of AUCs for CE-Iohexol and OMNIPAQUE was
1.0 with 94% confidence interval of 0.98-1.02. Geometric mean ratio
of Cmax for CE-Iohexol and OMNIPAQUE was 1.0 with 94% confidence
interval of 0.95-1.06.
- The means of AUC, Cmax, as well as half-life and elimination
constant, were similar between treatments; the mean elimination
constant was 0.3/hour for both treatments.
- Based on these results, it can be concluded that CE-Iohexol is
bioequivalent to the reference OMNIPAQUE following IV injection in
healthy adults.
- No subject had a serious adverse event or discontinued from the
study due to an adverse event. All adverse events were mild to
moderate in severity and the incidence of subjects with adverse
events was similar in both treatment groups.
- The most common adverse event was a sensation of warmth, which
is an adverse event known to occur during IV administration of
iodinated contrast agents such as OMNIPAQUE.3
- There were no clinically significant abnormal physical
examination findings, and there were no clinically meaningful
changes in vital signs, laboratory parameters., hematology,
urinalysis or ECG results.
- Overall, administration of the Captisol-containing CE-Iohexol
following IV injection was safe and well tolerated in normal
healthy subjects.
“This trial represents a promising milestone in the pursuit of a
safer agent for patients who receive intravenous contrast for their
radiology and cardiology tests and procedures,” said Peter A.
McCullough, MD, MPH, Vice Chief of Medicine, Baylor University
Medical Center, Dallas TX, and President, Cardiorenal Society of
America. “The results showed that this unique product candidate
incorporating a patented formulation ingredient had the expected
pharmacokinetic profile compared to the reference standard agent,
yet it offers potential for less kidney injury when given to
patients with baseline kidney disease, diabetes, and multiple
associated risk factors.”
About Captisol-enabled Iohexol
More than 30 million imaging procedures are performed each year
in the United States. Iodinated contrast agents represent more than
60% of all X-ray imaging agents sold with an annual U.S. market of
approximately $1.5 billion.4 Iohexol (marketed as OMNIPAQUE™ by GE
Healthcare), the most widely-used injectable diagnostic contrast
agent for imaging procedures, has global sales exceeding $500
million and no generic competition in the United States.
Contrast-induced acute kidney injury (CI-AKI) is the acute
impairment of renal function following intravascular administration
of an iodinated contrast agent, and occurs most frequently
following coronary angiography, percutaneous coronary intervention
and contrast-enhanced computed tomography, especially among
patients at risk of renal injury such as those with advanced age,
diabetes or heart failure. CI-AKI is an issue with broad medical
visibility as more than 50% of cardiovascular imaging procedures
are performed in patients age 65 or older.5
Currently no products are approved to prevent or treat CI-AKI in
this setting, and therefore Ligand believes a significant
opportunity exists for a safer formulation of contrast agents. The
goal is for CE-Iohexol to establish a new safety standard that
enables a future partner to gain meaningful market share.
About Captisol®
Captisol is a patent-protected, chemically modified cyclodextrin
with a structure designed to optimize the solubility and stability
of drugs. Captisol was invented and initially developed by
scientists in the laboratories of Dr. Valentino Stella, University
Distinguished Professor at the University of Kansas’ Higuchi
Biosciences Center for specific use in drug development and
formulation. This unique technology has enabled several
FDA-approved products, including Amgen’s KYPROLIS®, Baxter
International’s NEXTERONE®, Acrotech Biopharma L.L.C.’s and CASI
Pharmaceuticals’ EVOMELA® and Melinta Therapeutics’ BAXDELA™ and
Sage Therapeutics’ ZULRESSO™. There are many Captisol-enabled
products currently in various stages of development.
About Ligand Pharmaceuticals
Ligand is a biopharmaceutical company focused on developing or
acquiring technologies that help pharmaceutical companies discover
and develop medicines. Ligand’s business model creates value for
stockholders by providing a diversified portfolio of biotech and
pharmaceutical product revenue streams that are supported by an
efficient and low corporate cost structure. Ligand’s goal is to
offer investors an opportunity to participate in the promise of the
biotech industry in a profitable, diversified and lower-risk
business than a typical biotech company. Ligand’s business model is
based on doing what we do best: drug discovery, early-stage drug
development, product reformulation and partnering. Ligand partners
with other pharmaceutical companies to leverage what they do best
(late-stage development, regulatory management and
commercialization) to ultimately generate our revenue. Ligand’s
Captisol® platform technology is a patent-protected, chemically
modified cyclodextrin with a structure designed to optimize the
solubility and stability of drugs. OmniAb® is a patent-protected
transgenic animal platform used in the discovery of fully human
mono-and bispecific therapeutic antibodies. Ligand has established
multiple alliances, licenses and other business relationships with
the world's leading pharmaceutical companies including Amgen,
Merck, Pfizer, Bristol-Myers Squibb, Gilead, Janssen, Baxter
International and Eli Lilly.
Follow Ligand on Twitter @Ligand_LGND.
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 include statements regarding:
the potential that Ligand’s CE-Iohexol program to increase the
safety of widely-used commercial contrast agents; Ligand’s
expectations that the top-line Phase 1 clinical trial results can
support further clinical development or a new drug application to
the FDA in the future; the potential to partner or out-licensing
the CE-Iohexol program; the market size of contrast agent
procedures and the addressable market of CE-Iohexol; the potential
that CE-Iohexol could reduce renal toxicity and deliver a safer
radiocontrast agent; Ligand’s expectations that it will partner the
program or obtain a higher royalty rate or milestone payments due
to Ligand’s development activities; and Ligand’s view of that there
is a significant unmet need for safer radiocontrast agents. Actual
events or results may differ from our expectations. For example the
FDA may not agree with Ligand’s interpretation of the data Ligand
has reported; future clinical trials may demonstrate unexpected
adverse side effects or inadequate therapeutic efficacy of
CE-Iohexol may limit regulatory approval and/or commercialization,
or may result in recalls or product liability claims; Ligand may
choose to abandon the program for any reason or no reason; the
anticipated benefits of CE-Iohexol, including the possible
improvements in kidney safety, may not materialize; and Ligand may
be unable to secure licensing partners or buyers for products
developed from the contrast agent program. 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 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.
References
1. McCullough, J Am College of Cardiology 2016;68:1465-73 2.
Rowe ES, et al. Journal of Neuroimaging 2016; 26(5):511-8 3.
OMNIPAQUE (iohexol) injection [prescribing information]. GE
Healthcare, Inc.; April 2018. 4. Contrast Agents/Media Global
Market – Forecast to 2025 IQ4I Research & Consultancy Pvt.
Ltd., 2018 5. See:
http://www.onlinejacc.org/content/71/11_Supplement/A1637
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version on businesswire.com: https://www.businesswire.com/news/home/20191108005058/en/
Ligand Pharmaceuticals Incorporated Patrick O’Brien
investors@ligand.com (858) 550-7768 @Ligand_LGND
LHA Bruce Voss bvoss@lhai.com (310) 691-7100
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