Ligand Licensee Onyx Pharmaceuticals Receives FDA Accelerated Approval of
Kyprolis(TM) (carfilzomib) for Injection
SAN DIEGO, Jul 20, 2012 (BUSINESS WIRE) -- Ligand Pharmaceuticals Incorporated
(LGND) today announced that its licensee, Onyx Pharmaceuticals (ONXX), received
accelerated approval from the U.S. Food and Drug Administration (FDA) for
Kyprolis(TM) (carfilzomib) for Injection, a proteasome inhibitor indicated for
the treatment of patients with multiple myeloma who have received at least two
prior therapies, including bortezomib and an immunomodulatory agent, and have
demonstrated disease progression on or within 60 days of completion of the last
therapy. The indication for Kyprolis is based on response rate. Currently, no
data are available for Kyprolis that demonstrate an improvement in
progression-free survival or overall survival.
Kyprolis is formulated with Ligand's Captisol(R), which improves drug solubility
and enables a reduced drug load. Ligand is entitled to receive a $600,000
milestone payment from Onyx Pharmaceuticals; Ligand also is required to make a
payment of $3.5 million toward the former stockholders of CyDex Pharmaceuticals,
which Ligand acquired in 2011.
"We are very pleased with the FDA's decision and congratulate Onyx on this
significant achievement," said John Higgins, President and Chief Executive
Officer of Ligand Pharmaceuticals. "Our Captisol license agreement with Onyx is a
highly valuable asset for Ligand, and we look forward to the near-term launch of
the product. The approval of Kyprolis further demonstrates the clinical
advantages and commercial potential of Captisol."
The approval of Kyprolis was based on the results of the Phase 2b 003-A1 study, a
single-arm, multicenter clinical trial that enrolled 266 patients with multiple
myeloma, who had received a median of five prior anti-myeloma regimens. The
primary efficacy endpoint was overall response (ORR) and determined by an
Independent Review Committee using the International Myeloma Working Group (IMWG)
criteria. ORR was 22.9% and median response duration was 7.8 months.
Safety data were evaluated in 526 patients with relapsed and/or refractory
multiple myeloma who received single-agent carfilzomib. There were 37 deaths on
study, or 7% of patients. The most common causes of death, other than disease
progression, were cardiac (5 patients), end-organ failure (4 patients), and
infection (4 patients). Important warnings and precautions include cardiac
arrest, congestive heart failure, myocardial ischemia; pulmonary hypertension,
pulmonary complications, infusion reactions, infusion reactions, tumor lysis
syndrome, thrombocytopenia, hepatic toxicity and embryo-fetal toxicity. The most
common serious adverse reactions were pneumonia, acute renal failure, pyrexia,
and congestive heart failure. The most common adverse reactions (incidence of 30%
or greater) observed in clinical trials of patients with multiple myeloma were
fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and pyrexia.
Serious adverse reactions were reported in 45% of patients.
Full prescribing information is available at onyx.com.
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 at the University of Kansas' Higuchi
Biosciences Center for specific use in drug development and formulation. This
unique technology has enabled six FDA-approved products, including Onyx
Pharmaceuticals' Kyprolis(TM), Pfizer's Vfend(R)IV and Baxter International's
Nexterone(R). There are currently more than 20 Captisol-enabled products in
development, including The Medicines Company's MDCO-157 project and Rib-X's
Delafloxacin program.
Important Safety Information Regarding Kyprolis(TM) (carfilzomib) for Injection
Death due to cardiac arrest has occurred within a day of Kyprolis administration.
Patients with New York Heart Association Class III and IV heart failure,
myocardial infarction in the preceding 6 months, and conduction abnormalities
uncontrolled by medications were not eligible for the clinical trials. These
patients may be at greater risk for cardiac complications.
Pulmonary arterial hypertension (PAH) was reported in 2% of patients treated with
Kyprolis and was Grade 3 or greater in less than 1% of patients. Dyspnea was
reported in 35% of patients enrolled in clinical trials. Grade 3 dyspnea occurred
in 5%; no Grade 4 events, and 1 death (Grade 5) was reported.
Infusion reactions, characterized by a spectrum of systemic symptoms including
fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting,
weakness, shortness of breath, hypotension, syncope, chest tightness, or angina
can occur immediately following or up to 24 hours after administration of
Kyprolis. Administration of dexamethasone prior to Kyprolis reduces the incidence
and severity of reactions. Tumor lysis syndrome (TLS) occurred following Kyprolis
administration in < 1% of patients. Patients with multiple myeloma and a high
tumor burden should be considered to be at greater risk for TLS.
Thrombocytopenia following Kyprolis administration resulted in a dose reduction
in 1% of patients and discontinuation of treatment with Kyprolis in < 1% of
patients.
Cases of hepatic failure, including fatal cases, have been reported (< 1%).
Kyprolis can cause elevations of serum transaminases and bilirubin.
There are no adequate and well-controlled studies in pregnant women using
Kyprolis. Females of reproductive potential should be advised to avoid becoming
pregnant while being treated with Kyprolis.
About Ligand Pharmaceuticals
Ligand is a biopharmaceutical company with a business model that is based upon
the concept of developing or acquiring royalty revenue generating assets and
coupling them to 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 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 GlaxoSmithKline, Merck, Pfizer, Eli Lilly &
Company, Baxter International, Bristol-Myers Squibb, Celgene, Onyx
Pharmaceuticals, Lundbeck Inc., The Medicines Company, Curis, Inc. and Rib-X
Pharmaceuticals. Please visit captisol.com for more information on
Captisol. For more information on Ligand, please visit ligand.com.
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