Synergy Pharmaceuticals’ TRULANCE™ (Plecanatide) Receives U.S. FDA Approval for the Treatment of Adults with Chronic Idiopathic Constipation

NEW YORK–(BUSINESS WIRE)– Synergy Pharmaceuticals Inc. (NASDAQ:SGYP) announced today that the U.S.
Food and Drug Administration (FDA) has approved TRULANCE^™
(plecanatide) for the treatment of adults with chronic idiopathic
constipation (CIC). TRULANCE is the first drug designed to replicate the
function of uroguanylin, a naturally occurring and endogenous human
gastrointestinal (GI) peptide that is thought to stimulate fluid
secretion which results in a stool consistency associated with more
regular bowel function.

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“We are thrilled with the approval of TRULANCE because it provides an
additional, much-needed, new treatment option to help adults with
chronic idiopathic constipation and their healthcare providers manage
this condition,” said Gary S. Jacob, Ph.D., Chairman and CEO of Synergy
Pharmaceuticals Inc. “I am confident that we truly have the right team
with the right strategic vision and the right launch plan to
successfully bring TRULANCE into this large but underserved market.”

CIC is a complex, functional GI disorder defined by symptoms including
fewer than three bowel movements a week and hard-to-pass or incomplete
bowel movements, for which there is no identifiable cause.^1,2
CIC affects approximately 33 million Americans and an estimated 14
percent of the global population.²

The efficacy and safety of TRULANCE was evaluated in the largest Phase 3
CIC clinical trials to date, which included more than 2,600 patients in
two randomized, 12-week, double-blind, placebo-controlled studies of
TRULANCE.

Over 12 weeks, patients treated with TRULANCE achieved a significantly
greater efficacy responder rate — the primary endpoint defined by the
FDA for regulatory approval in CIC — in both studies compared to placebo
(Study 1: 21% vs. 10%; Study 2: 21% vs. 13%, p<0.005 for both studies).
Efficacy responders were defined as patients who had at least three
complete spontaneous bowel movements (CSBMs) in a given week and an
increase of at least one CSBM over baseline in the same week for at
least nine weeks out of the 12-week period, including at least three of
the last four weeks.

Over 12 weeks, patients who received TRULANCE in both studies also had
improvements as compared to placebo in stool frequency (as measured by
the number of spontaneous bowel movements per week), stool consistency
(as measured by the Bristol Stool Form Scale) and straining with bowel
movements.

« The impact of chronic constipation on the lives of affected patients is
often underestimated,” said William D. Chey, M.D., Professor of
Medicine, Director of the GI Physiology Laboratory, and Co-Director of
the Michigan Bowel Control Program at the University of Michigan.
“TRULANCE presents an exciting new treatment option for patients with
chronic constipation. Its efficacy and safety profile, plus its
negligible systemic absorption, are attractive attributes that make it a
welcome addition to our treatment options.”

In an integrated analysis of both studies, diarrhea was the most common
adverse reaction, reported in 5% of patients treated with TRULANCE
compared to 1% of patients treated with placebo. Overall discontinuation
rates were low among patients treated with TRULANCE and placebo (4% vs.
2%, respectively) and the most common adverse reaction leading to
discontinuation was diarrhea (2% for TRULANCE compared to 0.5% in
placebo).

The approved dosing regimen for TRULANCE is 3 mg taken orally, once
daily, with or without food at any time of the day. TRULANCE can be
swallowed whole or crushed in applesauce for those who are unable to
swallow medication.

TRULANCE will be available in the U.S. later this quarter.

Synergy has also completed two Phase 3 clinical trials for TRULANCE in
irritable bowel syndrome with constipation (IBS-C) and plans to file a
New Drug Application Supplement with Clinical Data (sNDA) later this
quarter with an expected 10-month review period from submission.

Indications and Usage

TRULANCE is a guanylate cyclase-C (GC-C) agonist indicated in adults for
the treatment of chronic idiopathic constipation (CIC).

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS
Trulance™
is contraindicated in patients less than 6 years of age; in nonclinical
studies in young juvenile mice administration of a single oral dose of
plecanatide caused deaths due to dehydration. Use of Trulance should be
avoided in patients 6 years to less than 18 years of age. The safety and
efficacy of Trulance have not been established in pediatric patients
less than 18 years of age.

Contraindications

• Trulance is contraindicated in patients less than 6 years of age due
  to the risk of serious dehydration.
• Trulance is contraindicated in patients with known or suspected
  mechanical gastrointestinal obstruction.

Warnings and Precautions

Risk of Serious Dehydration in Pediatric Patients

• Trulance is contraindicated in patients less than 6 years of age. The
  safety and effectiveness of Trulance in patients less than 18 years of
  age have not been established. In young juvenile mice (human age
  equivalent of approximately 1 month to less than 2 years), plecanatide
  increased fluid secretion as a consequence of stimulation of guanylate
  cyclase-C (GC-C), resulting in mortality in some mice within the first
  24 hours, apparently due to dehydration. Due to increased intestinal
  expression of GC-C, patients less than 6 years of age may be more
  likely than older patients to develop severe diarrhea and its
  potentially serious consequences.
• Use of Trulance should be avoided in patients 6 years to less than 18
  years of age. Although there were no deaths in older juvenile mice,
  given the deaths in young mice and the lack of clinical safety and
  efficacy data in pediatric patients, use of Trulance should be avoided
  in patients 6 years to less than 18 years of age.

Diarrhea

• Diarrhea was the most common adverse reaction in the two
  placebo-controlled clinical trials. Severe diarrhea was reported in
  0.6% of patients.
• If severe diarrhea occurs, the health care provider should suspend
  dosing and rehydrate the patient.

Adverse Reactions

• In the two combined CIC clinical trials, the most common adverse
  reaction in Trulance-treated patients (incidence ≥2% than in the
  placebo group) was diarrhea (5% vs 1% placebo).

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About Chronic Idiopathic Constipation (CIC)

CIC affects approximately 14 percent of the global population,
disproportionately affecting women and older adults.² People
with CIC have persistent symptoms of difficult and infrequent bowel
movements.¹ In addition to physical symptoms including
abdominal bloating and discomfort, CIC can adversely affect an
individual’s quality of life, including increasing stress levels and
anxiety.¹

About TRULANCE^™

TRULANCE^™ (plecanatide) is a once-daily tablet approved for
adults with CIC and is being evaluated for IBS-C. With the exception of
a single amino acid, TRULANCE is structurally related to uroguanylin, a
naturally occurring and endogenous human GI peptide. Uroguanylin is
thought to act in a pH-sensitive manner, targeting GC-C receptors
primarily in the small intestine coinciding with areas of fluid
secretion.

About Synergy Pharmaceuticals

Synergy is a biopharmaceutical company focused on the development and
commercialization of novel GI therapies. The company has pioneered
discovery, research and development efforts on uroguanylin analogs for
the treatment of functional GI disorders and inflammatory bowel disease.
Synergy’s proprietary uroguanylin analog platform includes two lead
product candidates – plecanatide and dolcanatide. For more information,
please visit www.synergypharma.com.

Forward-Looking Statement

This press release and any statements made for and during any
presentation or meeting contain forward-looking statements related to
Synergy Pharmaceuticals Inc. under the safe harbor provisions of Section
21E of the Private Securities Litigation Reform Act of 1995 and are
subject to risks and uncertainties that could cause actual results to
differ materially from those projected. These statements may be
identified by the use of forward-looking words such as « anticipate, »
« planned, » « believe, » « forecast, » « estimated, » « expected, » and « intend, »
among others. There are a number of factors that could cause actual
events to differ materially from those indicated by such forward-looking
statements. These factors include, but are not limited to, the
development, launch, introduction and commercial potential of TRULANCE;
growth and opportunity, including peak sales and the potential demand
for TRULANCE, as well as its potential impact on applicable markets;
market size; substantial competition; our ability to continue as a going
concern; our need for additional financing; uncertainties of patent
protection and litigation; uncertainties of government or third party
payer reimbursement; dependence upon third parties; our financial
performance and results, including the risk that we are unable to manage
our operating expenses or cash use for operations, or are unable to
commercialize our products, within the guided ranges or otherwise as
expected; and risks related to failure to obtain FDA clearances or
approvals and noncompliance with FDA regulations. As with any
pharmaceutical under development, there are significant risks in the
development, regulatory approval and commercialization of new products.
There are no guarantees that future clinical trials discussed in this
press release will be completed or successful or that any product will
receive regulatory approval for any indication or prove to be
commercially successful. Investors should read the risk factors set
forth in Synergy’s most recent periodic reports filed with the
Securities and Exchange Commission, including Synergy’s Form 10-K for
the year ended December 31, 2015. While the list of factors presented
here is considered representative, no such list should be considered to
be a complete statement of all potential risks and uncertainties.
Unlisted factors may present significant additional obstacles to the
realization of forward-looking statements. Forward-looking statements
included herein are made as of the date hereof, and Synergy does not
undertake any obligation to update publicly such statements to reflect
subsequent events or circumstances except as required by law.

¹ Thomas R, Luthin D. Current and emerging treatments for
irritable bowel syndrome with constipation and chronic idiopathic
constipation: focus on prosecretory agents. Pharmacotherapy Pub. 2015;
613-630.
² Suares NC, Ford AC. Prevalence of, and risk
factors for chronic idiopathic constipation in the community: systematic
review and meta-analysis. Am J Gastroenterol.
2011;106(9):1582-1591.

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