RALEIGH, N.C.–(BUSINESS WIRE)–Merz North America announced today that the U.S. Food and Drug
Administration (FDA) has approved the supplemental Biologics License
Application (sBLA) for XEOMIN^® (incobotulinumtoxinA)
for the treatment of chronic sialorrhea, or excessive drooling, in adult
patients. XEOMIN is the first and only neurotoxin with this approved
indication in the U.S.

“Until now, there has not been an FDA approved treatment for this
debilitating condition,” said Kevin O’Brien, Vice President and U.S.
Head of Neurosciences, Merz North America. “This approval represents a
significant milestone in addressing the unmet needs for more than
600,000 adults who suffer from chronic sialorrhea, and underscores our
commitment to improving the lives of those living with movement
disorders.”^1,2,3,4,5,6

Sialorrhea is a common symptom among patients who suffer from
neurological disorders including Parkinson’s disease, amyotrophic
lateral sclerosis (ALS), cerebral palsy (CP) or who have experienced a
stroke.^7,8 The condition can occur from difficulty retaining
saliva inside the mouth, issues with swallowing and from problems
controlling facial muscles.^7,9

The FDA granted this application a priority review designation upon
acceptance. Priority reviews are granted to drugs that will potentially
provide significant improvements in the safety and effectiveness of the
treatment, diagnosis or prevention of serious conditions.

XEOMIN was approved by the FDA for adult patients with sialorrhea and is
based on a Phase III, randomized, double-blind, placebo-controlled,
multicenter 184 patient trial. Both co-primary endpoints were
successfully achieved. A statistically significant improvement was
observed in change in unstimulated salivary flow rate (uSFR) and Global
Impression of Change Scale (GICS), both at week four as compared to
baseline pre-injection for subjects administered 100 U
incobotulinumtoxinA vs. placebo (p=0.004 and p=0.002, respectively).
GICS is a commonly used rating system for treatments of neurological
disorders by clinicians. Overall frequency of adverse events was similar
between placebo and treatment groups with no new or unexpected adverse
events reported. Subjects enrolled in the study received placebo (n=36),
incobotulinumtoxinA 75 U (n=74), or incobotulinumtoxinA 100 U (n=74).

This is the fourth neurological indication for XEOMIN, which was first
approved by the FDA in 2010 for the treatment of cervical dystonia and
blepharospasm (in patients previously treated with onabotulinumtoxinA)
in adult patients and later in 2015 for upper limb spasticity in adult
patients.

About Merz Neurosciences

Merz Neurosciences is a division of Merz North America and is deeply
committed to offering novel therapeutic options that address the largely
unmet medical needs that exist within the area of neuroscience. Merz
Neurosciences is an important contributor to the U.S. neurosciences
space and offers a portfolio that includes the neurotoxin XEOMIN^®
(incobotulinumtoxinA), the anticholinergic Cuvposa^®
(glycopyrrolate) Oral Solution and the Prolaryn^®
injectable implant family of products. To learn more about Merz
Neurosciences and its U.S. product portfolio, please visit www.merzusa.com/neurosciences.
For more information about Merz Neurosciences and its U.S. product
portfolio, please visit www.merzusa.com.

About Merz North America, Inc.

Merz North America, Inc. is a specialty healthcare company dedicated to
the development and marketing of innovative quality products for
physicians and patients across the United States and Canada. Merz
products are distributed through two divisions, Aesthetics and
Neurosciences, and are developed with the goal of improving patients’
health and quality of life by delivering therapies that bring about real
progress. Privately-held, Merz North America is headquartered in
Raleigh, North Carolina. To learn more about Merz North America, Inc.,
please visit www.merzusa.com.

About XEOMIN^® (incobotulinumtoxinA)

XEOMIN^® (incobotulinumtoxinA) is a prescription
medicine that is injected into muscles or glands and used to treat
adults with sialorrhea, increased muscle stiffness in the arm of adults
with upper limb spasticity, the abnormal head position and neck pain
that happens with cervical dystonia (CD) in adults, and to treat
abnormal spasm of the eyelids (blepharospasm) in adults who have had
prior treatment with onabotulinumtoxinA (Botox^®).

XEOMIN^® (incobotulinumtoxinA) IMPORTANT
CONSUMER SAFETY INFORMATION

Read the Medication Guide before you start receiving XEOMIN^®
(Zeo-min) and each time XEOMIN is given to you as there may be new
information. The risk information provided here is not comprehensive. To
learn more:

• Talk to your health care provider or pharmacist
• Visit www.xeomin.com
  to obtain the FDA-approved product labeling
• Call 1-844-4MYMERZ

Uses

XEOMIN is a prescription medicine used in adults:

• that is injected into glands that make saliva and is used to treat
  long-lasting (chronic) drooling (sialorrhea).
• that is injected into muscles and used to:
  • treat increased muscle stiffness in the arm because of upper limb
    spasticity.
  • treat the abnormal head position and neck pain with cervical
    dystonia (CD) in adults
  • who have and have not had prior treatment with botulinum toxin.
  • treat abnormal spasm of the eyelids (blepharospasm) in adults who
    have had prior
  • treatment with onabotulinumtoxinA (BOTOX^®).

It is not known if XEOMIN is safe and effective in children under 18
years of age.

Warnings

XEOMIN may cause serious side effects that can be life threatening.
Call your doctor or get medical help right away if you have any
of these problems anytime (hours to weeks) after treatment with
XEOMIN:

• Problems with swallowing, speaking, or breathing can happen within
  hours to weeks
• Problems with swallowing, speaking, or breathing can happen within
  hours to weeks after an injection of XEOMIN if the muscles that
  you use to breathe and swallow become weak. Death can happen as a
  complication if you have severe problems with swallowing or breathing
  after treatment with XEOMIN.
  • People with certain breathing problems may need to use muscles in
    their neck to help them breathe and may be at greater risk for
    serious breathing problems with XEOMIN.
  • Swallowing problems may last for several months, and during that
    time you may need a feeding tube to receive food and water. If
    swallowing problems are severe, food or liquids may go into your
    lungs. People who already have swallowing or breathing problems
    before receiving XEOMIN have the highest risk of getting these
    problems.
• Spread of toxin effects. In some cases, the effect of botulinum
  toxin may affect areas of the body away from the injection site and
  cause symptoms of a serious condition called botulism. The symptoms of
  botulism include: loss of strength and muscle weakness all over the
  body, double vision, blurred vision and drooping eyelids, hoarseness
  or change or loss of voice, trouble saying words clearly, loss of
  bladder control, trouble breathing, trouble swallowing.

These symptoms can happen hours to weeks after you receive an injection
of XEOMIN. These problems could make it unsafe for you to drive a car or
do other dangerous activities.

Do not take XEOMIN if you: are allergic to XEOMIN or any of the
ingredients in XEOMIN (see the end of this Guide for a list of
ingredients in XEOMIN), had an allergic reaction to any other botulinum
toxin product such as rimabotulinumtoxinB (Myobloc^®),
onabotulinumtoxinA (Botox^®, Botox^® Cosmetic), or
abobotulinumtoxinA (Dysport^®) or have a skin infection at the
planned injection site.

Before receiving XEOMIN, tell your doctor about all of your medical
conditions, including if you:

• have a disease that affects your muscles and nerves (such as
  amyotrophic lateral sclerosis [ALS or Lou Gehrig’s disease],
  myasthenia gravis or Lambert-Eaton syndrome)
• have had any side effect from any other botulinum toxin in the past
• have a breathing problem such as asthma or emphysema
• have a history of swallowing problems or inhaling food or fluid into
  your lungs (aspiration)
• have bleeding problems
• have drooping eyelids
• have plans to have surgery
• have had surgery on your face
• are pregnant or plan to become pregnant. It is not known if XEOMIN can
  harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if XEOMIN
  passes into breast milk.

Tell your doctor about all of the medicines you take, including
prescription and over-the-counter medicines, vitamins and herbal
supplements. Talk to your doctor before you take any new
medicines after you receive XEOMIN.

Using XEOMIN with certain other medicines may cause serious side effects
Do not start any new medicines until you have told your doctor
that you have received XEOMIN in the past. Especially tell your
doctor if you:

• have received any other botulinum toxin product in the last four months
• have received injections of botulinum toxin such as
  rimabotulinumtoxinB (MYOBLOC^®), onabotulinumtoxinA (BOTOX^®,
  BOTOX^® COSMETIC) and abobotulinumtoxinA (DYSPORT^®)
  in the past. Be sure your doctor knows exactly which product you
  received. The dose of XEOMIN may be different from other botulinum
  toxin products that you have received.
• have recently received an antibiotic by injection
• take muscle relaxants
• take an allergy or cold medicine
• take a sleep medicine

Ask your doctor if you are not sure if your medicine is one that is
listed above.

Know the medicines you take. Keep a list of your medicines with you to
show your doctor and pharmacist each time you get a new medicine.

Possible Side Effects
XEOMIN can cause serious side
effects including:
See “Warnings.”

• Injury to the cornea (the clear front surface of the eye) in people
  treated for blepharospasm. People who receive XEOMIN to treat
  spasm of the eyelid may have reduced blinking that can cause a sore on
  their cornea or other problems of the cornea. Call your healthcare
  provider or get medical care right away if you have eye pain or
  irritation after treatment with XEOMIN.

• XEOMIN may cause other serious side effects including allergic
  reactions. Symptoms of an allergic reaction to XEOMIN may include:
  itching, rash, redness, swelling, wheezing, trouble breathing, or
  dizziness or feeling faint. Tell your doctor or get medical help right
  away if you get wheezing or trouble breathing, or if you get dizzy or
  faint.

The most common side effects of XEOMIN in people with chronic
sialorrhea include:

• needing to have a tooth pulled.
• (extracted)
• dry mouth
• diarrhea
• high blood pressure

The most common side effects of XEOMIN in people with upper limb
spasticity include:

• seizure
• nasal congestion, sore throat and runny nose
• dry mouth
• upper respiratory infection

The most common side effects of XEOMIN in people with cervical
dystonia include:

• difficulty swallowing
• neck pain
• muscle weakness
• pain at the injection site
• muscle and bone pain

The most common side effects of XEOMIN in people with blepharospasm
include:

• drooping of the eyelid
• dry eye
• dry mouth
• diarrhea
• headache
• vision problems
• shortness of breath
• nasal congestion, sore throat, and runny nose
• respiratory infection

These are not all the possible side effects of XEOMIN.

Call your doctor for medical advice about side effects. You may report
side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of XEOMIN

Medicines are sometimes prescribed for purposes other than those listed
in a Medication Guide.

You can ask your pharmacist or doctor for information about XEOMIN that
is written for health professionals.

Active Ingredient: botulinum toxin type A

Inactive Ingredients: human albumin and sucrose

Copyright © 2018 Merz North America, Inc. All rights reserved. MERZ, the
MERZ logo, and XEOMIN are registered trademarks of Merz Pharma GmbH &
Co. KGaA. Botox, Dysport and Myobloc are registered trademarks of their
respective owners.

For more information, please see XEOMIN full Prescribing
Information and Medication
Guide.

______________________

1. Kowal SL, et al. (2013) Mov Disord. 28(3): 311-318

2. Kalf et al. J Neurol 2009; 256(9):1391-6.

3. Prevalence and Most Common Causes of Disability Among Adults —
United States, 2005. (2009, May 1). Retrieved June 28, 2018, from https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5816a2.htm

4. Walshe M et al. Cochrane Database Syst Rev. 2012;14:11.

5. Tiigimäe-Saar J et al. (2017) Clin Oral Invest. 21: 795-800

6. “What Is ALS?” ALSA.org, www.alsa.org/news/public-awareness/als-awareness-month/2016/what-is-als.html.

7. Hockstein, NG, et al. “Sialorrhea: a Management Challenge.” American
Family Physician Journal, 1 June 2004, pp. 2628–34. doi:https://www.ncbi.nlm.nih.gov/pubmed/15202698.

8. Dashtipour, Khashayar, et al. “RimabotulinumtoxinB in Sialorrhea:
Systematic Review of Clinical Trials.” Journal of Clinical
Movement Disorders, 6 June 2017, doi: 10.1186/s40734-017-0055-1.

9. Bavikatte, Ganesh, et al. “Management of Drooling of Saliva.” British
Journal of Medical Practitioners, vol. 5, no. 1, Mar. 2012, www.bjmp.org/content/management-drooling-saliva.