Apadaz is the First Prodrug of
Hydrocodone/Acetaminophen to be Approved by FDA
KemPharm, Inc. (NASDAQ:KMPH), a specialty pharmaceutical company
focused on the discovery and development of proprietary prodrugs,
announced today that the U.S. Food and Drug Administration (FDA)
approved its New Drug Application (NDA) for Apadaz™ for the
short-term (no more than 14 days) management of acute pain
severe enough to require an opioid analgesic and for which
alternative treatments are inadequate. Apadaz is an immediate
release (IR) combination of KemPharm’s prodrug, benzhydrocodone,
and acetaminophen (APAP).
“The approval of Apadaz is a significant
milestone for KemPharm as it creates the opportunity to introduce
what we believe is a differentiated product for the short-term
management of acute pain,” said Travis Mickle, Ph.D., KemPharm
President and Chief Executive Officer. “Based on its unique
properties, we firmly believe there is a commercial pathway for
Apadaz in what is a very high-volume market. We are excited
by the opportunity Apadaz offers to patients and for physicians who
now have the option of prescribing a differentiated product.”
“In addition to today’s approval, the U.S. Drug
Enforcement Administration (DEA) has indicated that it is their
intent to schedule Apadaz as a C-II product and will provide an
allocation of the Active Pharmaceutical Ingredient (API) consistent
with those scheduling provisions,” added Dr. Mickle. “This
prompt decision by the DEA essentially completes the regulatory
process with both Agencies and allows us to shift our focus towards
the product launch.”
“Finally, today is a validation of KemPharm’s
groundbreaking LATTM (Ligand Activated Therapy) platform and our
technological approach to drug development,” Dr. Mickle
closed. “KemPharm is first and foremost a prodrug development
company. The Apadaz approval highlights the value potential
that LAT™ offers in the discovery and development of proprietary
prodrugs that are designed to be differentiated versions of widely
prescribed, currently approved drugs, and that can successfully
complete the rigorous regulatory process.”
Conference Call
Information:
The company will host a conference call and live
audio webcast with slide presentation on Friday, February 23, 2018,
at 2:30 p.m. ET, to discuss the Apadaz approval by the FDA.
Interested participants and investors may access the conference
call by dialing either:
- (866) 395-2480 (U.S.)
- (678) 509-7538 (international)
- Conference ID: 9788408
The live webcast with accompanying slides will
be accessible via the Investor Relations section of the KemPharm
website http://investors.kempharm.com/. An archive of the webcast
and presentation will remain available following the call.
APADAZ™
Apadaz was developed from KemPharm’s proprietary
LATTM (Ligand Activated Therapy) platform technology and is
intended for the short-term (no more than 14 days) management
of acute pain severe enough to require an opioid analgesic and for
which alternative treatments are inadequate. KemPharm believes
Apadaz is unique among prescription opioids in that it contains a
prodrug that is chemically inert, or inactive, on its own.
When ingested, enzymes in the gastrointestinal tract cleave the
ligand from the prodrug (benzhydrocodone) and release the parent
drug (hydrocodone), which can then exert its therapeutic
effect. The final approved product labeling for Apadaz
includes these and other data points but concludes that the overall
results of the clinical program did not demonstrate
abuse-deterrence by current measurement standards.
The approval of Apadaz via the 505(b)(2) pathway
was based in part on pharmacokinetic studies with Vicoprofen®,
Ultracet®, and Norco® in which Apadaz demonstrated exposure to
hydrocodone and acetaminophen (APAP) that is expected to result in
therapeutic effects equivalent to currently approved
immediate-release hydrocodone/APAP combination products when
administered orally as intended.
Indication:Apadaz contains an
opioid agonist and acetaminophen and is indicated for the
short-term (no more than 14 days) management of acute pain
severe enough to require an opioid analgesic and for which
alternative treatments are inadequate.
Limitations of Use:Because of
the risks of addiction, abuse, and misuse with opioids, even at
recommended doses, reserve Apadaz for use in patients for whom
alternative treatment options [e.g., non-opioid analgesics] have
not been or are not expected tolerated, or have not provided
adequate analgesia, or are not expected to provide adequate
analgesia.
Important Safety
Information:
Apadaz is contraindicated in patients with:
significant respiratory depression; acute or severe bronchial
asthma in an unmonitored setting or in absence of resuscitative
equipment; known or suspected gastrointestinal obstruction,
including paralytic ileus; and hypersensitivity to hydrocodone or
acetaminophen.
Apadaz contains benzhydrocodone, a Schedule II
controlled substance. Apadaz can be abused and is subject to
misuse, addiction, and criminal diversion.
Potential risks associated with Apadaz include
addiction, abuse, and misuse, life-threatening respiratory
depression, neonatal opioid withdrawal syndrome, risks of
concomitant use or discontinuation of cytochrome P450 CYP3A4
inhibitors and inducers, acetaminophen hepatoxicity risks from
concomitant use with benzodiazepines or other CNS depressants, risk
of life-threatening respiratory depression in patients with chronic
pulmonary disease or in elderly, cachectic, or debilitated
patients, adrenal insufficiency, severe hypotension, serious skin
reactions, risks of use in patients with increased intracranial
pressure, brain tumors, head injury, or impaired consciousness,
hypersensitivity/anaphylaxis, risks of use in patients with
gastrointestinal conditions, risk of use in patients with seizure
disorders, and withdrawal, risks of driving and operating
machinery.
Potential drug interactions with Apadaz
include:
- Serotonergic Drugs: Concomitant use may result in serotonin
syndrome. Discontinue Apadaz if serotonin syndrome is
suspected.
- Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics:
Avoid use with Apadaz because they may reduce analgesic effect of
APADAZ or precipitate withdrawal symptoms.
- Monoamine Oxidase Inhibitors (MAOIs): Can potentiate the
effects of hydrocodone. Avoid concomitant use in patients receiving
MAOIs or within 14 days of stopping treatment with an MAOI.
Most common adverse reactions (>5%) are
nausea, somnolence, vomiting, constipation, pruritus, dizziness,
and headache.
The Full Prescribing Information for Apadaz
contains the following Boxed Warning:
WARNING: ADDICTION, ABUSE, AND MISUSE;
LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION;
NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4
INTERACTION; HEPATOTOXICITY; and RISKS FROM CONCOMITANT USE WITH
BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
Addiction, Abuse, and
Misuse:
Apadaz exposes patients and other users to the
risks of opioid addiction, abuse, and misuse, which can lead to
overdose and death. Assess each patient’s risk prior to prescribing
Apadaz and monitor all patients regularly for the development of
these behaviors and conditions.
Life-Threatening Respiratory
Depression:
Serious, life-threatening, or fatal respiratory
depression may occur with use of Apadaz. Monitor for
respiratory depression, especially during initiation of Apadaz or
following a dose increase.
Accidental Ingestion:
Accidental ingestion of even one dose of Apadaz,
especially by children, can result in a fatal overdose of
hydrocodone.
Neonatal Opioid Withdrawal
Syndrome:
Prolonged use of Apadaz during pregnancy can
result in neonatal opioid withdrawal syndrome, which may be
life-threatening if not recognized and treated, and requires
management according to protocols developed by neonatology
experts. If prolonged opioid use is required in a pregnant
woman, advise the patient of the risk of neonatal opioid withdrawal
syndrome and ensure that appropriate treatment will be
available.
Cytochrome P450 3A4
Interaction:
The concomitant use of Apadaz with all
cytochrome P450 3A4 inhibitors may result in an increase in
hydrocodone plasma concentrations, which could increase or prolong
adverse reactions and may cause potentially fatal respiratory
depression. In addition, discontinuation of a concomitantly used
cytochrome P450 3A4 inducer may result in an increase in
hydrocodone plasma concentration. Monitor patients receiving Apadaz
and any CYP3A4 inhibitor or inducer.
Hepatotoxicity:
Apadaz contains acetaminophen. Acetaminophen has
been associated with cases of acute liver failure, at times
resulting in liver transplant and death. Most of the cases of liver
injury are associated with the use of acetaminophen at doses that
exceed 4000 milligrams per day, and often involve more than
one acetaminophen-containing product.
Risks From Concomitant Use With
Benzodiazepines Or Other CNS Depressants:
Concomitant use of opioids with benzodiazepines
or other central nervous system (CNS) depressants, including
alcohol, may result in profound sedation, respiratory depression,
coma, and death.
- Reserve concomitant prescribing of Apadaz and benzodiazepines
or other CNS depressants for use in patients for whom alternative
treatment options are inadequate.
- Limit dosages and durations to the minimum required.
- Follow patients for signs and symptoms of respiratory
depression and sedation.
For Important Safety Information including full
prescribing information, visit: www.kempharm.com
About KemPharm:
KemPharm is a specialty pharmaceutical company
focused on the discovery and development of proprietary prodrugs to
treat serious medical conditions through its proprietary LATTM
(Ligand Activated Therapy) platform technology. KemPharm
utilizes its proprietary LATTM platform technology to generate
improved prodrug versions of FDA-approved drugs in the high need
areas of ADHD, pain and other central nervous system disorders.
KemPharm’s co-lead clinical development candidates are KP415 and
KP484, both based on a prodrug of methylphenidate, but with
differing extended-release/effect profiles for the treatment of
ADHD. In addition, the company has received FDA approval for
Apadaz™, an immediate-release combination product candidate of
benzhydrocodone, a prodrug of hydrocodone, and acetaminophen.
The company is also advancing KP201/IR, an acetaminophen-free
immediate-release formulation of the company’s benzhydrocodone
prodrug candidate. Both Apadaz™ and KP201/IR are intended for the
treatment of acute pain severe enough to require an opioid
analgesic and for which alternative treatments are inadequate. For
more information on KemPharm and its pipeline of prodrug product
candidates visit www.kempharm.com.
Caution Concerning Forward Looking
Statements:
This press release may contain forward-looking
statements made in reliance upon the safe harbor provisions of
Section 27A of the Securities Act of 1933, as amended, and Section
21E of the Securities Exchange Act of 1934, as amended.
Forward-looking statements include all statements that do not
relate solely to historical or current facts, and can be identified
by the use of words such as “may,” “will,” “expect,” “project,”
“estimate,” “anticipate,” “plan,” “believe,” “potential,” “should,”
“continue” or the negative versions of those words or other
comparable words. Forward-looking statements are not guarantees of
future actions or performance. These forward-looking statements are
based on information currently available to KemPharm and its
current plans or expectations and are subject to a number of
uncertainties and risks that could significantly affect current
plans. Risks concerning KemPharm’s business are described in detail
in KemPharm's Annual Report on Form 10-K for the year ended
December 31, 2016, and KemPharm’s other Periodic and Current
Reports filed with the Securities and Exchange Commission.
KemPharm is under no obligation to (and expressly disclaims any
such obligation to) update or alter its forward-looking statements,
whether as a result of new information, future events or
otherwise.
Investor Contacts: |
|
Media Contact: |
Jason
Rando / Joshua Drumm, Ph.D.Tiberend Strategic Advisors,
Inc.212-375-2665 / 2664jrando@tiberend.comjdrumm@tiberend.com |
|
Daniel L. CohenExecutive VP, Government and Public
RelationsKemPharm, Inc.202-329-1825dcohen@kempharm.com |
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