Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) today announced that the FDA
has granted tentative approval for UCERIS® (budesonide) rectal foam for
the induction of remission in patients with active mild-to-moderate
distal ulcerative colitis (UC) extending up to 40cm from the anal verge.
The foam is a rectally administered corticosteroid that overcomes
treatment limitations associated with currently approved therapies which
are often ineffective due to insufficient distribution of active drug to
the distal colon.
The FDA’s tentative approval of this product means that Salix’s product
meets all of the FDA’s manufacturing quality and clinical safety and
efficacy standards and will be granted final approval upon the
resolution of patent issues. Salix anticipates resolution of patent
issues early in the fourth quarter of 2014 and the launch of UCERIS
rectal foam during the first quarter of 2015.
“Distal ulcerative colitis can be challenging for patients to live with
and gastroenterologists to treat. Our goal is to put the disease into
remission so that patients can get on with their lives,” said Bill
Forbes, Executive Vice President, Medical and Research and Development
and Chief Development Officer, Salix. “The unique delivery system of
UCERIS rectal foam can help overcome current treatment limitations by
reaching the affected area of the distal colon and keeping the
medication there long enough to be effective. People suffering from
distal UC now have another option to consider when facing this disease.”
Two identically designed, randomized, double-blind, placebo-controlled
Phase III studies found that a significantly greater percentage of
patients receiving UCERIS 2mg rectal foam achieved remission of distal
ulcerative colitis at six weeks compared with placebo (41.2% vs 24.0%).
Significantly more patients treated with UCERIS rectal foam also
achieved key secondary outcome measures compared with placebo at six
weeks, including a Modified Mayo Disease Activity Index (MMDAI)
endoscopy score of 0 or 1 in 55.6% versus 43.2% in the first trial and
56.0% vs 36.7% in the second trial.
A significantly greater percentage of patients treated with UCERIS
rectal foam experienced improvement in rectal bleeding within the first
two weeks of treatment (twice daily dosing); this percentage increased
and was maintained after an additional two and four weeks of treatment
once a day. At week six, the percentage of patients achieving MMDAI
rectal bleeding score of 0 was 46.6% vs 28.0% in the first trial and
50.0% vs 28.6% in the second trial.
“These trials definitively demonstrated that UCERIS rectal foam is an
efficacious and well-tolerated rectal therapy for the induction of
remission in patients with mild-to-moderate distal UC. Treatment with
UCERIS rectal foam also led to a rapid response for rectal bleeding that
was sustained through the sixth week of the trial,” said William
Sandborn, MD, Chief, Division of Gastroenterology and Director, UCSD IBD
Center, University of California San Diego and UC San Diego Health
System, and principle investigator of the trials. “This unique treatment
modality allows the medication to reach the target area and stay there
long enough to work. UCERIS rectal foam is a welcome addition to the
treatment options available to gastroenterologists and their patients
coping with this complex disease.”
UC is a chronic disease of the large intestine, also known as the colon,
in which the lining of the colon becomes inflamed and develops tiny open
sores, or ulcers, that produce pus and mucous. The combination of
inflammation and ulceration can cause abdominal discomfort and frequent
emptying of the colon. Distal ulcerative colitis is characterized as
either ulcerative proctitis (inflammation localized to the rectum) or
ulcerative proctosigmoiditis (inflammation localized to the distal colon
and rectum).
The Crohn’s and Colitis Foundation of America (CCFA) estimates that UC
may affect as many as 700,000 Americans. While most people are diagnosed
in their mid-30’s, the disease can occur at any age and equally affects
men and women. An estimated 46% of people with UC have a diagnosis of
distal UC.
About half of all patients with ulcerative colitis experience at least
mild symptoms including persistent diarrhea accompanied by abdominal
pain and blood in the stool and more urgent bowel movements. CCFA also
notes that people suffering from UC often experience loss of appetite
and may lose weight as a result. A feeling of low energy and fatigue is
also common.
Rectal therapy is recommended for the induction of remission in patients
with mild-to-moderate ulcerative proctitis, and recommended alone or in
combination with oral aminosalicyclic acid (ASA) for mild-to-moderate
distal UC. However, currently available rectal therapies have
limitations, including difficulty of administration and retention
(enemas) and limited proximal spread (suppositories).
About the Phase III Clinical Trials
Two identically designed, randomized, double-blind, placebo-controlled
Phase III studies were conducted with the goal of evaluating the
efficacy and safety of UCERIS rectal foam for induction of remission in
patients with mild-to-moderate distal ulcerative colitis. The studies
were funded by Salix Pharmaceuticals, Inc.
A total of 546 patients with endoscopically confirmed mild-to-moderate
active distal UC extending ≥5cm, but no further than 40cm from the anal
verge, and baseline MMDAI score between 5 and 10, inclusive, with
subscale ratings of 2 or 3 for endoscopic appearance and rectal bleeding
were eligible for the studies. Patients were randomized 1:1 to receive
UCERIS rectal foam (2 mg/25 mL; n=267) or placebo (n=279) twice daily
for two weeks, then once daily for four weeks. Concomitant use of oral
5-ASAs at doses up to 4.8 g/d was permitted. Demographic and baseline
disease characteristics were generally comparable across groups.
UCERIS rectal foam was well tolerated and the adverse event profile was
consistent with other studies of rectal budesonide in this patient
population. The most commonly-reported side effects included: decreased
blood cortisol levels (17.2%); adrenal insufficiency (3.7%); and, nausea
(2.2%) and headache (2.2%).
Important Safety Information for UCERIS rectaI foam:
UCERIS (budesonide) rectal foam is contraindicated in patients with a
history of a known hypersensitivity to budesonide or any of the
ingredients of UCERIS rectal foam. Reactions have included anaphylaxis.
When glucocorticosteroids are used chronically, systemic effects such as
hypercorticism and adrenal suppression may occur. Since UCERIS rectal
foam contains a glucocorticosteroid, general warnings concerning
glucocorticoids should be followed.
Care is needed in patients who are transferred from glucocorticosteroid
treatment with higher systemic effects to glucocorticosteroids with
lower systemic effects, such as UCERIS rectal foam, since symptoms
attributed to withdrawal of steroid therapy, including those of acute
adrenal suppression or benign intracranial hypertension, may develop.
Taper patients slowly from systemic corticosteroids if transferring to
UCERIS rectal foam. Monitor for withdrawal symptoms and unmasking of
allergies.
Patients who are on drugs that suppress the immune system are more
susceptible to infection than healthy individuals. Monitor patients with
active or quiescent tuberculosis infection, untreated fungal, bacterial,
systemic viral or parasitic infections, or ocular herpes simplex. More
serious or even fatal courses of chickenpox or measles can occur in
susceptible patients.
Monitor patients with hypertension, diabetes mellitus, osteoporosis,
peptic ulcer, glaucoma or cataracts, or with a family history of
diabetes or glaucoma, or with any other condition where
glucocorticosteroids may have unwanted effects.
The contents of UCERIS rectal foam are flammable. Instruct
the patient to avoid fire, flame and smoking during and immediately
following administration.
Concomitant use of inhibitors of Cytochrome P450 3A4 (for example
ketoconazole and erythromycin) should be avoided and patients should be
closely monitored for increased signs and/or symptoms of hypercorticism.
Avoid grapefruit juice, which is known to inhibit CYP3A4, when taking
UCERIS rectal foam.
Based on animal data, UCERIS rectal foam may cause fetal harm.
Patients with moderate to severe hepatic impairment should be monitored
for increased signs and/or symptoms of hypercorticism.
In clinical studies, the most common adverse reactions (incidence ≥ 2%)
were decreased blood cortisol, adrenal insufficiency, and nausea.
Please see complete Prescribing Information for UCERIS rectal foam.
About UCERIS® (budesonide) rectal foam
Budesonide is a high potency corticosteroid that was developed to
minimize the systemic adverse consequences of classic corticosteroids,
such as hydrocortisone, which have higher levels of systemic absorption.
In several large studies UCERIS rectal foam was highly effective in the
treatment of distal ulcerative colitis. Clinical trials suggest that the
foam formulation demonstrates improved reach (or spread) and rapid
distribution of budesonide to the sigmoid colon and the rectum, without
the difficulties and inconvenience associated with retention of enema
formulations. These trials also suggest that the foam provides more
immediate and targeted therapy for distal ulcerative colitis than is
available with oral therapies. The foam formulation for rectal
administration was designed to improve both the patient’s ability to
retain the drug in the rectum following administration as well as
distribution of the active drug to the rectum and sigmoid colon. Salix
licensed UCERIS rectal foam from Dr. Falk Pharma. The product was
approved in Europe in 2006 and is marketed in Europe by Dr. Falk Pharma.
Full prescribing data for UCERIS® (budesonide) rectal foam is available
at www.salix.com.
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 market them through Salix’s
gastroenterology specialty sales and marketing team.
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 web site is not
incorporated in our filings with the SEC.
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: uncertainty that Uceris (budesonide) 2 mg
rectal foam will be commercially successful; market acceptance for
approved products; 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.
Copyright Business Wire 2014