Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) and Progenics Pharmaceuticals,
Inc. (NASDAQ:PGNX) today announced that the Food and Drug Administration
has approved RELISTOR® (methylnaltrexone bromide)
Subcutaneous Injection, 12 mg/0.6ml, for the treatment of opioid-induced
constipation (OIC) in patients taking opioids for chronic non-cancer
pain. RELISTOR subcutaneous injection is currently the only available
peripherally acting mu opioid receptor antagonist (PAMORA) that is
approved for treating OIC at the cause without interfering with the
centrally acting analgesic properties of the opioid.
“Frequently, opioid analgesics are prescribed to manage pain in patients
suffering from chronic conditions. Unfortunately, the use of an opioid
can result in debilitating constipation for a significant number of
these patients,” stated Bill Forbes, Executive Vice President, Medical,
Research and Development and Chief Development Officer, Salix. “The
approval and availability of RELISTOR for treating the underlying cause
of OIC provides an important and welcomed advancement for many patients
who experience constipation while taking opioids for chronic non-cancer
pain.”
Traditional laxative treatments are often ineffective for many chronic
pain patients suffering with opioid-induced constipation. Approximately
80% of chronic pain patients with OIC that were taking laxative therapy
continued to report difficulties dealing with their constipation
symptoms, as documented by a large patient survey published in 2008 in Pain
Medicine. One third of these chronic pain patients reported stopping
or lowering their opioid dose in order to relieve their opioid induced
constipation, resulting in increased pain levels.
“Unlike other opioid-related side effects, such as nausea and vomiting,
constipation never goes away,” said Eugene Viscusi, MD, Director of
Acute Pain Management, Department of Anesthesiology at Thomas Jefferson
University in Philadelphia. “Constipation is one of the side effects for
which patients do not develop tolerance with chronic exposure. It can be
a significant burden affecting a patient’s ability to function
adequately.”
Dr. Viscusi continued, “Patients generally experience a rapid bowel
movement following administration of methylnaltrexone, often within 30
minutes. Unlike laxatives, RELISTOR offers patients a relatively
predictable timed response for a bowel movement. Additionally, most
patients describe the sensation like a normal bowel activity. These
attributes of treatment with RELISTOR are tremendous advantages.”
About the Phase III Clinical Trial for OIC in chronic non-cancer pain
A randomized, double blind, placebo-controlled trial was conducted to
evaluate the efficacy and safety of RELISTOR 12mg once daily for the
treatment of opioid induced constipation in patients with chronic
non-cancer pain.
A total of 312 patients with a history of non-cancer pain and taking
opioids for at least one month prior to study entry were eligible for
enrollment. Patients also had confirmed OIC defined at <3 spontaneous
bowel movements per week during the screening period. Constipation due
to opioid use had to be associated with 1 or more of the following: A
Bristol Stool Form Scale score of 1 or 2 for at least 25% of the bowel
movements (BM), straining during at least 25% of the BMs or a sensation
of incomplete evacuation after at least 25% of the BMs. The median
duration of opioid-induced constipation at baseline was 59 months. The
median daily baseline oral morphine equivalent dose was 161 mg. Patients
were randomized to receive RELISTOR 12 mg or placebo once daily for four
weeks followed by an eight week open label phase when patients could
take medications as needed.
In the study a significantly greater portion of patients taking RELISTOR
12mg daily reported having three or more spontaneous bowel movements
(SBM) per week during the four week double blind period compared to
placebo (59% vs. 38%). Following the first dose, 33% of patients in the
RELISTOR 12 mg once daily treatment group had a SBM within 4 hours and
approximately half of patients had a SBM prior to the second dose of
RELISTOR.
RELISTOR subcutaneous injection was well tolerated and the adverse event
profile was consistent with other studies of RELISTOR in an advanced
illness population. The most commonly reported side effects included:
abdominal pain (21%), diarrhea (6%), nausea (9%) and hyperhidrosis (6%)
About Opioids, Constipation and RELISTOR (methylnaltrexone bromide)
Opioid analgesics are frequently prescribed for patients with chronic
pain, including patients with advanced illness. An estimated 27 million
patients in the US take opioids for chronic pain. Constipation is one of
the most common and distressing side effects in patients receiving
chronic opioid therapy. Approximately 40% of chronic pain patients, or
nearly 11 million patients, on opioid therapy will experience OIC.
RELISTOR is the first approved medication that specifically targets the
underlying cause of OIC.
RELISTOR is a Peripherally Acting Mu Opioid Receptor Antagonist (PAMORA)
specifically designed to block the constipating effects of opioids in
the gastrointestinal tract. The unique molecular structure of RELISTOR
restricts it from crossing the blood-brain barrier and interfering with
the analgesic effect of opioids.
RELISTOR Subcutaneous Injection was approved in the United States in
2008 for the treatment of OIC in patients with advanced illness who are
receiving palliative care, when response to laxative therapy has not
been sufficient. The use of RELISTOR beyond four months has not been
studied in the advanced illness population. The drug is also approved
for use in over 50 countries worldwide, including the European Union,
Canada, and Australia. In the 28 member countries of the E.U., as well
as Iceland, Norway and Liechtenstein, RELISTOR is approved for the
treatment of OIC in advanced illness patients who are receiving
palliative care when response to usual laxative therapy has not been
sufficient. In Canada, the drug is approved for the treatment of OIC in
patients with advanced illness, receiving palliative care. When response
to laxatives has been insufficient, RELISTOR should be used as an
adjunct therapy to induce a prompt bowel movement. Applications in
additional countries are pending. RELISTOR is under license to Salix
Pharmaceuticals, Inc. from Progenics Pharmaceuticals, Inc.
For more information about RELISTOR, please visit www.RELISTOR.com
Important Safety Information about RELISTOR
RELISTOR® (methylnaltrexone bromide) Subcutaneous Injection
is contraindicated in patients with known or suspected gastrointestinal
obstruction and patients at increased risk of recurrent obstruction, due
to the potential for gastrointestinal perforation.
Cases of gastrointestinal perforation have been reported in adult
patients with opioid-induced constipation and advanced illness with
conditions that may be associated with localized or diffuse reduction of
structural integrity in the wall of the gastrointestinal tract (e.g.,
peptic ulcer disease, Ogilvie’s syndrome, diverticular disease,
infiltrative gastrointestinal tract malignancies or peritoneal
metastases). Take into account the overall risk-benefit profile when
using RELISTOR in patients with these conditions or other conditions
which might result in impaired integrity of the gastrointestinal tract
wall (e.g., Crohn’s disease). Monitor for the development of severe,
persistent, or worsening abdominal pain; discontinue RELISTOR in
patients who develop this symptom.
If severe or persistent diarrhea occurs during treatment, advise
patients to discontinue therapy with RELISTOR and consult their
physician.
Symptoms consistent with opioid withdrawal, including hyperhidrosis,
chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in
patients treated with RELISTOR. Patients having disruptions to the
blood-brain barrier may be at increased risk for opioid withdrawal
and/or reduced analgesia and should be monitored closely for adequacy of
analgesia and symptoms of opioid withdrawal.
Avoid concomitant use of RELISTOR with other opioid antagonists because
of the potential for additive effects of opioid receptor antagonism and
increased risk of opioid withdrawal.
RELISTOR may precipitate opioid withdrawal in a fetus and should be used
during pregnancy only if the potential benefit justifies the potential
risk to the fetus. In nursing mothers, a decision should be made to
discontinue nursing or discontinue the drug, taking into account the
importance of the drug to the mother.
In the clinical study in adult patients with opioid-induced constipation
and chronic non-cancer pain, the most common adverse reactions (≥ 1%)
were abdominal pain, nausea, diarrhea, and hyperhidrosis, hot flush,
tremor, and chills.
In clinical studies in adult patients with opioid-induced constipation
and advanced illness, the most common adverse reactions (≥ 5%) were
abdominal pain, flatulence, nausea, dizziness, and diarrhea.
Please see complete Prescribing Information for RELISTOR.
About Salix
Salix Pharmaceuticals, Ltd., headquartered in Raleigh, North Carolina,
develops and markets prescription pharmaceutical products and medical
devices for the prevention and treatment of gastrointestinal diseases.
Salix’s strategy is to in-license late-stage or marketed proprietary
therapeutic products, complete any required development and regulatory
submission of these products, and commercialize them through the
Company’s 500-member specialty sales force.
Salix markets XIFAXAN® (rifaximin) tablets 200 mg and 550 mg,
MOVIPREP® (PEG 3350, sodium sulfate, sodium chloride,
potassium chloride, sodium ascorbate and ascorbic acid for oral
solution, 100 g/7.5 g/2.691 g/1.015 g/5.9 g/4.7 g), OSMOPREP®
(sodium phosphate monobasic monohydrate, USP, and sodium phosphate
dibasic anhydrous, USP) Tablets, APRISO® (mesalamine)
extended-release capsules 0.375 g, UCERIS® (budesonide)
extended release tablets, for oral use, UCERIS (budesonide) rectal foam,
GIAZO® (balsalazide disodium) tablets, COLAZAL®
(balsalazide disodium) Capsules, GLUMETZA® (metformin
hydrochloride extended-release tablets) 500 mg and 1000 mg, ZEGERID®
(omeprazole/sodium bicarbonate) Powder for Oral Suspension, ZEGERID®
(omeprazole/sodium bicarbonate) Capsules, METOZOLV® ODT
(metoclopramide hydrochloride), RELISTOR® (methylnaltrexone
bromide) Subcutaneous Injection, FULYZAQ® (crofelemer)
delayed-release tablets, SOLESTA®, DEFLUX®,
RUCONEST® C1 esterase inhibitor (recombinant), PEPCID® (famotidine)
for Oral Suspension, DIURIL® (chlorothiazide) Oral
Suspension, AZASAN® (azathioprine) Tablets, USP, 75/100 mg,
ANUSOL-HC® 2.5% (Hydrocortisone Cream, USP), ANUSOL-HC®
25 mg Suppository (Hydrocortisone Acetate), PROCTOCORT® Cream
(Hydrocortisone Cream, USP) 1% and PROCTOCORT® Suppository
(Hydrocortisone Acetate Rectal Suppositories) 30 mg, CYCLOSET®
(bromocriptine mesylate) tablets, FENOGLIDE® (fenofibrate)
tablets. RELISTOR® oral tablet, encapsulated bowel
preparation and rifaximin for additional indications are under
development.
For full prescribing information and important safety information on
Salix products, including BOXED WARNINGS for OSMOPREP, AZASAN, GLUMETZA
and METOZOLV, please visit www.salix.com
where the Company promptly posts press releases, SEC filings and other
important information or contact the Company at 919 862-1000.
Salix trades on the NASDAQ Global Select Market under the ticker symbol
“SLXP”.
For more information, please visit our website at www.salix.com
or contact Salix at 919-862-1000. Follow us on Twitter (@SalixPharma)
and Facebook (www.facebook.com/SalixPharma).
Information on our Twitter feed, Facebook page and website is not
incorporated in our filings with the SEC.
About Progenics
Progenics Pharmaceuticals, Inc. is developing innovative medicines for
oncology, with a pipeline that includes several product candidates in
late-stage clinical development. Progenics’ first-in-class PSMA targeted
technology platform includes an antibody drug conjugate therapeutic in a
two-cohort phase 2 clinical trial and a small molecule targeted imaging
agent that has completed dosing in a phase 2 trial. Among other assets
in its pipeline of targeted radiotherapy and molecular imaging compounds
is Azedra™, an ultra-orphan radiotherapy candidate also in a
phase 2 study under an SPA. Progenics’ first commercial product, Relistor®
(methylnaltrexone bromide) for opioid-induced constipation, is partnered
with and marketed by Salix Pharmaceuticals, Inc.
Additional information concerning Progenics and its business may be
available in press releases or other public announcements and public
filings made after this release.
For additional information, please visit www.progenics.com.
Information on or accessed through our website is not included in the
company's SEC filings. Follow us on LinkedIn.
Salix Disclosure Notice
Please Note: The statements provided herein that are not historical
facts are or might constitute projections and other forward-looking
statements regarding future events. Although we believe the expectations
reflected in such forward-looking statements are based on reasonable
assumptions, our expectations might not be attained. Forward-looking
statements are just predictions and are subject to known and unknown
risks and uncertainties that could cause actual events or results to
differ materially from expected results. Factors that could cause actual
events or results to differ materially from those described herein
include, among others: market acceptance for approved product including
new indications for RELISTOR; uncertainties as to the ability to
successfully complete the proposed Cosmo transaction in accordance with
its terms and in accordance with the expected schedule; the possibility
that competing offers will be made; the possibility that various closing
conditions for the proposed Cosmo transaction may not be satisfied or
waived, including that a governmental entity may prohibit or refuse to
grant any approval required for the consummation of the proposed
transaction; the unpredictability of the duration and results of
regulatory review of New Drug Applications, Biologics License
Agreements, and Investigational NDAs; generic and other competition in
an increasingly global industry; litigation and the possible impairment
of, or inability to obtain, intellectual property rights and the costs
of obtaining such rights from third parties in an increasingly global
industry; the cost, timing and results of clinical trials and other
development activities involving pharmaceutical products; post-marketing
approval regulation, including the ongoing Department of Justice
investigation of Salix’s marketing practices; revenue recognition and
other critical accounting policies; the need to acquire new products;
changes in tax laws or interpretations thereof; general economic and
business conditions; and other factors. Readers are cautioned not to
place undue reliance on the forward-looking statements included herein,
which speak only as of the date hereof. Salix does not undertake to
update any of these statements in light of new information or future
events, except as required by law. The reader is referred to the
documents that Salix files from time to time with the SEC.
Progenics Disclosure Notice
This press release may contain projections and other forward-looking
statements regarding future events. Such statements are predictions
only, and are subject to risks and uncertainties that could cause actual
events or results to differ materially. These risks and uncertainties
include, among others: the cost, timing and results of clinical trials
and other development activities; the unpredictability of the duration
and the results of regulatory review of New Drug Applications and
Investigational NDAs; market acceptance for approved products; generic
and other competition; the possible impairment of, inability to obtain
and costs of obtaining intellectual property rights; and possible safety
or efficacy concerns, general business, financial and accounting
matters, litigation and other risks. More information concerning
Progenics and such risks and uncertainties is available on its website,
and in its press releases and reports it files with the U.S. Securities
and Exchange Commission. Progenics is providing the information in this
press release as of its date and does not undertake any obligation to
update or revise it, whether as a result of new information, future
events or circumstances or otherwise.
Copyright Business Wire 2014