Carnexiv is the first FDA-approved
intravenous carbamazepine option
Ligand earns $1.25 million milestone payment
to be recognized in the fourth quarter
Ligand Pharmaceuticals Incorporated (NASDAQ: LGND)
partner Lundbeck announced today that the U.S. Food and Drug
Administration (FDA) has approved Carnexiv™ (carbamazepine)
injection as a short-term replacement therapy for oral
carbamazepine formulations in adults with certain seizure types
when oral administration is temporarily not feasible. Carnexiv
received orphan drug designation for this indication and will be
the first available intravenous (IV) formulation of the
antiepileptic drug (AED) carbamazepine. Lundbeck plans to make
Carnexiv commercially available in the United States in early 2017.
With the approval, Ligand has earned a $1.25 million milestone
payment. Ligand is also entitled to receive a royalty of 2.75% on
net sales of Carnexiv.
Carnexiv is a short-term (≤7 days) intravenous replacement
therapy for oral carbamazepine formulations that provides
continuity of care for adult patients who are unable to take
carbamazepine by mouth and have the following seizure types:
- Partial seizures with complex
symptomatology
- Generalized tonic-clonic seizures
- Mixed seizure patterns which include
the above, or other partial or generalized seizures
As with the oral carbamazepine formulation, there is a risk of
serious dermatologic reactions during treatment with Carnexiv,
including toxic epidermal necrolysis (TEN) and Stevens-Johnson
syndrome (SJS), as well as a risk of aplastic anemia and
agranulocytosis.
Partial seizures and generalized tonic-clonic seizures can often
be difficult to control.1 As a result, many patients with epilepsy
are on a daily regimen of one or more AEDs that has been carefully
adjusted to obtain a therapeutic response. Switching or an abrupt
discontinuation of AEDs can lead to seizure recurrence or
breakthrough seizures.2,3
Researchers at the University of Minnesota College of Pharmacy
helped conduct early clinical proof-of-concept studies, which were
instrumental in developing the formulation of Carnexiv, making
intravenous administration possible. James Cloyd, PharmD, Angela
Birnbaum, PhD and Ilo E. Leppik, MD at the University of Minnesota
partnered closely with Lundbeck during the clinical trial and
approval process for Carnexiv.
Ligand’s previous outlook for third quarter 2016 revenue was
approximately one-third of the projected total revenues for the
second half of 2016 of $66 million to $70 million. The Carnexiv
approval milestone had been anticipated for the third quarter and
now will be recognized in the fourth quarter.
About Carnexiv™ (carbamazepine) injection
Carnexiv is an intravenous antiepileptic drug developed in the
United States by Lundbeck and approved for use in the United
States. Carnexiv is a short-term (≤7 days) replacement therapy for
oral carbamazepine for patients who are unable to take medication
by mouth. When switching from oral carbamazepine, the total daily
dosage of Carnexiv should be 70 percent of the total daily dose of
oral carbamazepine, divided equally into four separate 30-minute
infusions separated by 6 hours. At the end of the intravenous
replacement period, patients should be switched back to their
previous oral carbamazepine total daily dose and frequency as soon
as clinically appropriate.
Indications and Usage
CARNEXIV (carbamazepine) injection is indicated as replacement
therapy for oral carbamazepine formulations, when oral
administration is temporarily not feasible, in adults with the
following seizure types:
- Partial seizures with complex
symptomatology
- Generalized tonic-clonic seizures
- Mixed seizure patterns which include
the above, or other partial or generalized seizures
Limitations of Usage
CARNEXIV is not indicated for the treatment of absence seizures
(including atypical absence). Carbamazepine has been associated
with increased frequency of generalized convulsions in these
patients.
Important Safety
Information
WARNING: SERIOUS DERMATOLOGIC REACTIONS
and APLASTIC ANEMIA AND AGRANULOCYTOSIS
See full prescribing information for
complete boxed warning.
Serious
Dermatologic Reactions
- Serious and sometimes fatal
dermatologic reactions, including toxic epidermal necrolysis (TEN)
and Stevens-Johnson syndrome (SJS), have occurred with
carbamazepine. Discontinue CARNEXIV if these reactions
occur
- Patients of Asian ancestry have a
10-fold greater risk of TEN/SJS, compared to other populations.
Avoid use of CARNEXIV in genetically at-risk patients, including
those positive for the HLA-B*1502 allele
Aplastic Anemia
and Agranulocytosis
- Aplastic anemia and agranulocytosis
can occur with CARNEXIV
- Obtain complete CBC prior to
initiation of CARNEXIV. Consider discontinuing CARNEXIV if
significant bone marrow depression develops
Contraindications: Bone Marrow Depression, Hypersensitivity,
and Concomitant Drugs
- Patients with bone marrow depression or
a known hypersensitivity to carbamazepine or tricyclic
antidepressants. If patient or immediate family member has history
of hypersensitivity, consider benefits and risks and closely
monitor for symptoms
- Concomitant use with boceprevir,
nefazodone, and delavirdine or other non-nucleoside reverse
transcriptase inhibitors
- Use of monoamine oxidase inhibitors
(MAOIs) within the past 14 days before beginning carbamazepine
treatment
Toxic Epidural Necrolysis (TEN), Stevens-Johnson syndrome
(SJS), HLA-B*1502 Allele, and Aplastic Anemia and Agranulocytosis
(see Boxed Warning)
Renal Impairment
CARNEXIV should generally not be used in patients with moderate
or severe renal impairment. Closely monitor patients with renal
impairment.
Drug Reaction with Eosinophilia and Systemic Symptoms
(DRESS)
DRESS, also known as multiorgan hypersensitivity, has occurred
with carbamazepine. These events can be fatal or life-threatening.
Advise patients to report signs and symptoms such as fever, rash,
lymphadenopathy, and/or facial swelling immediately, and
discontinue CARNEXIV if an alternative etiology cannot be
established.
Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including CARNEXIV, increase the
risk of suicidal thoughts or behavior. Monitor patients for the
emergence or worsening of depression, any unusual changes in mood
or behavior, or suicidal thoughts, behavior, or thoughts of
self-harm; and instruct families and caregivers to report behaviors
of concern immediately.
Pregnancy Registry and Nursing Mothers
- CARNEXIV can cause fetal harm when
administered to a pregnant woman. If used during pregnancy, or if
the patient becomes pregnant while taking CARNEXIV, inform the
patient of the potential risk to the fetus and carefully consider
both the potential risks and benefits of treatment. Encourage
patients to call the toll-free number 1-888-233-2334 to enroll in
the Pregnancy Registry or visit
http://www.aedpregnancyregistry.org/.
- Discontinue CARNEXIV or discontinue
nursing, taking into consideration the importance of the drug to
the mother.
Abrupt Discontinuation and Seizure Risk
Do not discontinue CARNEXIV abruptly because of the risk of
seizures, status epilepticus, and other withdrawal
signs/symptoms.
Hyponatremia
Hyponatremia can result from treatment with CARNEXIV, and in
many cases appears to be caused by the syndrome of inappropriate
antidiuretic hormone secretion (SIADH). The risk of SIADH appears
to be dose-related. Elderly patients and patients treated with
diuretics are at a greater risk. Consider discontinuing CARNEXIV in
patients with symptomatic hyponatremia.
Neurologic Function
Carbamazepine has the potential to impair judgment, cognition,
motor function, and motor coordination, and it may also cause
dizziness, ataxia, and drowsiness. Caution patients about operating
hazardous machinery, including automobiles, until they are
reasonably certain that carbamazepine does not affect them
adversely.
Hepatic Toxicity
Hepatic effects, ranging from slight elevations in liver enzymes
to rare cases of hepatic failure, have been reported, and may
progress despite drug discontinuation. Rare instances of vanishing
bile duct syndrome have also been reported. Evaluate liver function
before and during treatment, particularly in patients with a
history of liver disease. Discontinue CARNEXIV based on clinical
judgment in the case of active liver disease, or with newly
occurring or worsening clinical or laboratory evidence of liver
dysfunction or hepatic damage. Avoid using CARNEXIV in patients
with a history of hepatic porphyria.
Increased Intraocular Pressure
Carbamazepine has mild anticholinergic activity. Consider
assessing intraocular pressure before initiating and periodically
during therapy in patients with a history of increased intraocular
pressure.
Hepatic Porphyria
Avoid using CARNEXIV in patients with a history of hepatic
porphyria, as acute attacks have been reported in such patients and
CARNEXIV increases porphyrin precursors in rodents.
Drug Interactions
Carbamazepine may reduce plasma concentrations of concomitant
medications metabolized by CYP1A2, 2B6, 2C9/19 and 3A4; closely
monitor carbamazepine levels and make appropriate dose adjustments.
CYP3A4 inhibitors can increase plasma carbamazepine levels. CYP3A4
inducers can decrease carbamazepine levels.
Adverse Reactions
The most common adverse reactions with CARNEXIV (incidence ≥2%)
were dizziness, somnolence, blurred vision, diplopia, headache,
infusion-related reaction, infusion site pain, and anemia. The most
common adverse reactions with oral carbamazepine were dizziness,
drowsiness, unsteadiness, nausea, and vomiting.
Important Dosing Information
Use of CARNEXIV for more than 7 days has not been studied and is
not recommended. At the end of intravenous (IV) replacement
therapy, switch patients back to oral carbamazepine at their
previous total daily oral dose and frequency as soon as clinically
appropriate.
Please see the full Prescribing Information, including
Boxed Warning for serious dermatologic reactions and aplastic
anemia and agranulocytosis, for complete details; or go
to www.CARNEXIV-US.com for more information.
CARNEXIV is a trademark of Lundbeck.All other trademarks or
registered trademarks are the property of their respective
owners.
About Ligand Pharmaceuticals
Ligand is a biopharmaceutical company focused on developing or
acquiring technologies that help pharmaceutical companies discover
and develop medicines. Our 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. Our 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. Our business model is
based on doing what we do best: drug discovery, early-stage drug
development, product reformulation and partnering. We partner 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 Novartis,
Amgen, Merck, Pfizer, Celgene, 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
Lundbeck’s plans to make Carnexiv commercially available in early
2017; Ligand’s future revenue; the timing of the $1.25 million
payment payable to Ligand; the potential for Carnexiv to provide
alternative treatment to AED carbamazepine; and the description of
the side effects and commercial opportunity for Carnexiv. Actual
events or results may differ from our expectations. For example,
there can be no assurances that Lundbeck will successfully launch
Carnexiv in 2017, if ever; the side effects or efficacy of Carnexiv
may prove different or worse than the results from previous
clinical trials; and Carnexiv may not be accepted as a treatment
option by doctors and other health professionals. In addition,
there can be no assurance that Lundbeck will make the required
milestone payment. 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.
Sources
- Mattson R, Cramer J, et al. A
comparison of valproate with carbamazepine for the treatment of
complex partial seizures and secondarily generalized tonic-clonic
seizures in adults. N Engl J Med. 1992. 327(11):765-71.
- Finamore JM, Sperling MR, et al.
Seizure outcome after switching antiepileptic drugs: A matched,
prospective study. Epilepsia. 2016 57(8):1294-300.
- Wang SP, Mintzer ST, et al. Seizure
recurrence and remission after switching antiepileptic drugs.
Epilepsia 2013. 54:187-193
View source
version on businesswire.com: http://www.businesswire.com/news/home/20161007005818/en/
Ligand Pharmaceuticals IncorporatedTodd Pettingill,
858-550-7500investors@ligand.comorLHABruce Voss,
310-691-7100bvoss@lhai.com
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