Zinc: Neurobion - Neurobion Neonin

PR toolbox - GCH-NEU-1704-0081(1)

New Clinical Study

TOOLBOX AND PROGRAM 2017
 Dear Colleagues,

I’m delighted to share with you the new Nenoin toolbox, which focuses on the
positive benefits of treating peripheral neuropathy symptoms with Neurobion Forte.

We now have the results of a 12-week non-interventional clinical study with more
than 400 patients, which was conducted recently in Indonesia in 8 centres.
The treatment provided to patients was Neurobion Forte, a combination of vitamin
B1 (100mg), B6 (100mg) and B12 (5000μg). Patients were suffering from mild to
moderate peripheral neuropathy (PN) from multiple etiologies. Currently there is only
a limited number of existing studies conducted on many etiologies, as most studies
focus on one or few etiologies. The study provided an extremely clear and positive
outcome, which is promising news for all PN sufferers in terms of improvement on
the symptoms, longer term benefits as well as tolerance profile.

The toolbox provides you with a multitude of always on assets including an

HCP leaflet, press release, animated infographic and quotes from KOLs. These assets
can be used during a medical symposium, with media, as well as directly with HCPs and
should be leveraged in an ecosystem, across Paid, Earned and Shared.
Please make sure that the toolbox activation is aligned
with local Medical and Communication areas.

You can use this toolbox to share these very positive outcomes with healthcare
professionals and beyond. Please keep the Global Team informed of your efforts and
do not hesitate to get in touch should you require further guidance or support for
implementing local activities.

We look forward to hearing back from you!

Best wishes,
Toolbox team

2
Contents

1. Campaign overview 4

a. Brand challenge 4

b. Toolbox objectives 4

c. Key target audiences 4

d. Step by step guidance 5

2. Activation assets 6

a. Key messages 6

b. Reveal 7

1. Press release 7

2. Clinical study leaflet 9

3. Clinical study summary 11

c. Sustain assets 12

4. Animated infographic 12

5. Quote cards from the study investigators 15

d. Equip Sales team 18

6. Clinical study advertorial 18

7. Clinical study specific Q&As 19

3. Evaluation guide 21

3
1. Campaign overview
a. Brand challenge
Convince front line HCPs about the efficiency of Neurobion Forte (neurotropic B vitamins
combination) to effectively reduce PN symptoms already after 14 days and constantly improving over
3 months of treatment.

b. Toolbox objectives
Create assets which can be leveraged as soon as the study is published and then always on. The assets
can be leveraged through various phases of the 4Cs: to catch attention of the HCPs, to convince them,
as well as to continue conversation. The assets should be leveraged with paid media, as well as to earn
interest and finally should be also featured on the owned media channels.

Please note that all assets needs to be checked by local MLR prior to local use.
In particular all claims need to be checked locally
to ensure that the clinical study outcome is sufficient to support these.

Celebrate the good news of a new clinical study run on vitamin B combinations.
Reveal the outcome of this new clinical study.
Engage HCPs and media to share the 3 key takeaway from the observational, non-interventional study:
1. Treatment efficacy: a treatment with Neurobion Forte tablets (neurotropic B vitamins
combination) has shown proven benefits on all symptoms of peripheral neuropathy observed in
the clinical observational, non-interventional study – this treatment can be considered for all
patients with mild and moderate symptoms, independently from the etiology.
2. Treatment duration: an improvement after 2 weeks of treatment should be observed.
Consider extending the treatment as the improvement on symptoms further increases (no plateau
effect seen in the study, up to 90 days of treatment).
3. Tolerance profile: a long term treatment can be recommended as it has shown a good tolerance
profile over the whole duration of the study (three months).

c. Key target audiences

HCPs
This toolbox has been developed to include material relevant to help a broad spectrum of HCPs involved
in neuropathy and who may be in contact and/or treat patients with neuropathy. This target group
covers both specialized and non-specialized HCPs audience: typically, the assets will be relevant to primary
care physicians, specialists (neurologists, endocrinologists/diabetologist or orthopaedists) as well as
pharmacists. Please note that the toolbox does not provide assets customized for a specific
target audience (e.g. no targeted assets for pharmacists).

4
MEDICAL/HCP MEDIA
One of the main objectives of this toolbox is to reach HCPs through the media they consume, to drive
further education and awareness. Please bear in mind that medical media is still among the most
trusted sources of information for HCPs, independently from their speciality: indeed a piece of content
which an HCP reads about in a medical journal will be seen as more credible than when the same
content is presented directly by sales force.

NON-MEDICAL/HCP MEDIA
Non-specialized media might also be interested in the outcome of a new clinical study, for example news
media, daily print media or specific consumer media for seniors.

KEY TARGET MARKETS

Indonesia, Brazil, Philippines, Mexico, CENTRO, Peru, Andean, South Africa, Portugal, Malaysia, Thailand,
Vietnam, Hong Kong and the Middle East.
Note: All countries which market Neurobion 5000 should leverage the toolbox with Neurobion branding,
with the exception of the KOL quote cards. The countries which market a Neurobion combination which
contains B1, B6 and B12 but not Neurobion 5000 should use the material unbranded.

d. Step by step guidance

Plan budget for implementation
Translate content and have it locally approved

Reveal the Sustain interest and Equip Sales team to

clinical study outcome own clinical study outcome educate HCPs

Share outcome of the
clinical study with HCP media
and non HCP media
Upload content on
Continue to spread the
digital platforms available
news about the clinical study
for HCPs
directly among HCPs

Assets:
Assets: press release (1), Assets:
clinical study advertorial (6),
clinical study leaflet (2), animated infographic (4),
clinical study Q&A (7)
clinical study summary (3) quote cards (5)

Share back after activation: plan, timeline, learnings and results

5
2. Activation assets
a. Key messages
Key messages are an essential part of a communications plan - they enable
a story to be accurately and precisely replicated in multiple settings while
remaining faithful to the facts. By their very nature, key messages are vital
Guidance
and are designed to provide the essential building blocks to any external,
stakeholder engagement. Using these key messages will help you to
maintain focus for this communication program per the strategic objectives.

A new robust clinical observational, non-interventional study¹ validates successful treatment of

peripheral neuropathy with a combination of neurotropic B vitamins (Neurobion Forte).
The combination of vitamin B1 (100mg), B6 (100mg) and B12 (5000μg) with Neurobion Forte taken
once per day is effective to significantly relieve symptoms of Peripheral Neuropathy of different
etiologies as of 14 days of treatment.
Additionally, the impact was further improved with longer treatment duration at 30 days, 60 days and
90 days.
The combination of neurotropic B vitamins (Neurobion Forte) has also shown a good tolerance profile
over the whole duration of the study (3 months).
Neurobion Forte is a combination of neurotropic B vitamins. Vitamins B1 (thiamine), B6 (pyridoxine)
and B12 (cobalamin) are known to have particularly important neurotropic roles to play in the
maintenance, nourishment and regeneration of nerves²,³, more specifically in neurotransmitter synthesis,
myelin synthesis and nerve membrane function.

References:
1 Management of peripheral neuropathy symptoms with a fixed dose combination of high dose vitamin B1, B6 and B12: A 12 week
prospective non-interventional study in Indonesia, Asian Journal of Medical Sciences, January 2018.
2 Jolivalt et all, 2009, B vitamins alleviate indices of neuropathic pain in diabetic rats, Eur J Pharmacol, 10;612(1-3):41-7.
3 Becker et all 1990, A contribution to the scientific assessment of degenerative and regenerative processes
in peripheral nerve fibers, Neurochirurgia.

6
b. Reveal
1. Press release

Despite the changing methods to achieve media coverage, the press

release remains the centre of any PR campaign. A well written and
targeted press release will attract media attention to your campaign
Guidance and help you to gain editorial, non-paid for media coverage.
Please ensure that all press releases are reviewed locally before use,
especially in countries where Neurobion Forte is a prescription product.

New observational, non-interventional clinical study -

a giant leap for taking care of peripheral neuropathy sufferers
Clinical study shows benefits on symptoms of peripheral neuropathy

Darmstadt, Germany, Jan 2018 - Peripheral neuropathy sufferers treated with a combination of three neurotropic
B vitamins, the active ingredients of Neurobion have experienced improvement on all neuropathy symptoms observed
in the study, independently from the cause of their neuropathy.

NERVES SENSORY
MOTOR
The nervous system allows us to perceive, comprehend, and respond
to the world around us. It coordinates voluntary actions like walking
and involuntary actions like breathing and swallowing. Nerves, the
components of the nervous tissue, enable impulses of sensation and
motion between the brain, spinal cord and other parts of the body.

PERIPHERAL NEUROPATHY

as tingling, increased or decreased sensitivity to vibration, hot or cold, numbness, muscle weakness and even burning
pain. Peripheral Neuropathy can cause “typical symptoms“ which appear more often and “atypical“ symptoms, which
are less frequent and can be overlooked or misinterpreted.
Example of symptoms of Peripheral Neuropathy:

Paresthesia Numbness Burning pain Sharp pain

Symptoms of peripheral neuropathy can seem innocuous but have an impact of the patients’ well-being and their

OBSERVATIONAL, NON-INTERVENTIONAL CLINICAL STUDY CONFIRMS THE BENEFITS

OF A UNIQUE TREATMENT FOR ALL
A new clinical study (Asian Journal of Medical Sciences, Jan 2018) has brought a major step forward for nerve

regardless of the cause of peripheral neuropathy.

itching, often felt in the arms and feet), they experienced relief on all these symptoms. It was also observed that the
longer they used the treatment, the more relief the patients felt from these symptoms.
Finally it is also very reassuring to see that the treatment has shown a good tolerance profile over
the whole duration (3 months).

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QUICK FACTS AND SUMMARY
Causes and risk factors of peripheral neuropathy are multiple and include conditions such as:

nutritional deficiencies e.g. vitamin B deficiency…. and other unexplained causes1.

Neurobion Forte treatment:

disease. The symptoms were even more reduced over longer duration of treatment (for a 3 months period tested) and
the treatment was well tolerated.

MORE INFORMATION ABOUT NEUROBION

• Neurobion, the nerve care expert from Merck Consumer Health has been first launched in Austria in 1962 and
is now a world leader in neurotropic B vitamins combination products.
• Neurotropic B vitamins are vitamins exerting their benefits on the health of nervous system. They have an

health or peripheral neuropathy

• Neurobion is available on prescription/OTC (adapt based on country).

ABOUT MERCK’S CONSUMER HEALTH BUSINESS

The Consumer Health business of Merck aims at preparing society for a new era of humans living 100 healthy years. For this
purpose, the business supports the so-called WE100®
accordingly. The leading “lovebrands” of Merck’s Consumer Health business, such as Neurobion®, Bion®, Nasivin®, Seven Seas®,
Dolo-Neurobion®, and Femibion® support this overarching purpose through consumer-inspired innovation.
The Consumer Health business is with over 3,800 employees globally active in over 40 markets. The portfolio comprises of brands
with annual total sales of about $ 1 billion. Consumer Health is a business of the Healthcare business sector within the Merck
Group with global headquarters in Darmstadt, Germany. For more information please go to www.merck-consumer-health.com or
https://twitter.com/merck_ch.

ABOUT MERCK GROUP

Merck is a leading science and technology company in healthcare, life science and performance materials. Around 50,000
employees work to further develop technologies that improve and enhance life – from biopharmaceutical therapies to treat cancer
or multiple sclerosis, cutting-edge systems for scientific research and production, to liquid crystals for smartphones and LCD
televisions. In 2016, Merck generated sales of € 15 billion in 66 countries.
Founded in 1668, Merck is the world’s oldest pharmaceutical and chemical company. The founding family remains the majority
owner of the publicly listed corporate group. Merck holds the global rights to the Merck name and brand. The only exceptions are
the United States and Canada, where the company operates as EMD Serono, MilliporeSigma and EMD Performance Materials.

1 Head 2006

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 2. Clinical study leaflet

This is a tool you can use to speak with the target audience about
the outcome of the clinical study. The guide can be left with clients;
Guidance alternatively, it can be made available in downloadable form on your website.
Please review all assets locally with MLR before local activation.

Non-interventional
clinical study shows
benefits on symptoms of
peripheral neuropathy,
of multiple etiologies

a
combination of 3 neurotropic B vitamins
– by Neurobion Forte – have experienced
significant improvements
in symptoms observed in the study

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PERIPHERAL NEUROPATHY: A COMPLEX DISEASE WHICH
NEEDS TO BE DETECTED AND TREATED AS EARLY AS POSSIBLE
The peripheral nervous system is an essential part of a
functioning body: it works by sensing stimuli (such as touch
or vibration) and sending signals to the central nervous
system (spinal cord and brain) for processing (perception).
The peripheral nervous system also communicates the signals
as muscle movement following burning a finger on a hot pan.
Neuropathy, characterized by impaired nerve function, is
the interruption of this process whereby essential signals
are disrupted, resulting in a disturbance in the transmission
of information. More specifically, peripheral neuropathy (PN)
interferes with the neurons of the peripheral nervous system.
Neuropathy is a complex condition and can have multiple
causes. The pathophysiology of peripheral neuropathy is very
complex, there are typical populations which are at higher
risk but in many patients neuropathy can also have more than
one case.
WHAT PUTS PATIENT AT RISK? 1
Chronic disease, like diabetes
Environmental toxins e.g. smoking
Alcoholism
Nutritional deficiencies e.g. B vitamin deficiency
Genetic predisposition
CLINICAL STUDY SUMMARY: an observational, non-interventional clinical study validates
successful treatment of peripheral neuropathy with a combination of neurotropic B vitamins
HEALTHY NERVOUS TISSUE STUDY OBJECTIVE: the main objective of the
clinical study was to evaluate the improvement
Normal nervous tissue: in clinical symptoms of peripheral neuropathy
the distribution and density of according to total symptom score (TSS) from
myelinated fibers is normal Baseline up to 3 months of treatment when treated
with a combination of neurotropic B vitamins.
should be studied, as well as the impact on quality
of life and the tolerability of the treatment.
MILD TO MODERATE PERIPHERAL CLINICAL STUDY DESIGN: the 12 weeks
NEUROPATHY prospective non-interventional clinical study
(add published reference, when available)
Loss of myelinated nerve fibers was conducted in Indonesia and has involved
is presented. 411 patients, between 18 and 65 years, with
peripheral neuropathy symptoms. Importantly,
the study methodology involved patients from
Ability to regenerate is visible
by groups of small regenerating multiple etiologies, such as diabetes, carpal tunnel
axons syndrome as well as idiopathic PN and others. It
is all the more important to highlight this point
that there is only a very limited number of clinical
studies done on PN from multiple etiologies.
SEVERE PERIPHERAL NEUROPATHY The eligible subjects received Neurobion Forte
(combination of vitamin B1-100mg; vitamin
Rarefication of axons.
B6-100mg and vitamin B12-5000μg) orally once
daily after meals as prescribed by physicians in
Severe reduction
their normal practice.
of fiber density.
STUDY PARAMETERS: the primary parameter studied
was the total symptom score (TSS) focusing on burning
pain, stabbing pain, paresthesia, numbness. The secondary
parameter was a visual analogue scale (VAS) of the following
symptoms: burning, paresthesia, numbness, tingling and pain
and the SF8 evaluating the QoL of patients.
STUDY RESULTS: the non-interventional clinical study
provided extremely clear and positive outcome, bearing
promising news for all PN sufferers.
• It appears clearly that the combination of vitamin
B1 (100mg), B6 (100mg) and B12 (5000μg) with
etiologies. (as measured by TSS)
• Indeed, the clinical symptoms of Peripheral Neuropathy
have shown significant improvement as of visit 2 (14
days after start of treatment). Additionally, the impact
was further improved with longer treatment duration at
30 days, 60 days and 90 days: longer treatment duration
shows a higher benefit for the patient.
• Finally, it is equally important to note that the treatment
with a combination of neurotropic B vitamins (Neurobion
Forte) has also shown a good tolerance profile over
the whole duration of the study (3 months) and had a

Low ability to regenerate

Other unexplained causes nerve fibers.

PRACTICAL TAKEOUT Impact on Neurobion Forte treatment

(mean value) on PN sufferers’ symptoms (TSS)
FOR HEALTHCARE PROFESSIONALS
Peripheral Neuropathy can manifest itself through a Because of the prevalence of PN in diabetes a large 7

1
large variety of symptoms, depending on the parts of number of the research around treatment has focused 6
a treatment with Neurobion 5.451±2.0365

on diabetic neuropathy; in fact, there is only a very limited

Forte tablets (neurotropic B vitamins combination) 5

symptoms of PN can vary among individuals in both, type number of studies looking at treatments for peripheral 4.358±1,9148
has shown benefits on all symptoms of peripheral 4
and presentation, there are some typical symptoms, which neuropathy of other etiology than diabetes. 3.551±1.6919
neuropathy observed in the clinical study
are more common, such as numbness, tingling, sensation 3

– this treatment can be considered for all patients 2.786±1.4801

impairments, paraesthesia, burning pain and stabbing pain. Within the treatment guidelines, several treatment 2.020±1.2808
with mild and moderate symptoms, independently 2

Atypical symptoms include for example muscle cramps, options for neuropathic pain are available. These are from the etiology. 1

unstable gait/dizziness and muscle twitching. essentially focusing on neuropathic pain and do not

2
necessarily address the earlier stages of neuropathy, when 0

Treatment duration: an improvement after 2 visit 1 visit 2 (14 days) visit 3 (30 days) visit 4 (60 days) visit 5 (90 days)

Nerves are naturally repaired via regeneration, this is a the symptoms are mild to moderate. Additionally, these
Total Symptom Score (TSS)
natural process of restoring nerve function. However,
was increasing progressively with longer treatment Stabbing plan Burning pain Paresthesia Numbness

this natural process can be disturbed by certain conditions.
Unfortunately, when approximately 50% or more of nerve
fibres are damaged, the point of no return occurs wherein
the discovery of new proof indicating that an alternative
duration, therefore long term treatment is more
beneficial for the patient.
population is extremely promising: a new robust study

regeneration is not possible any longer. This is why early
diagnosis and treatment are vital to avoid reaching the
“point of no return”.
3
Good tolerance profile: the treatment has shown
combination and provides an indication on the required
a good tolerance profile over the whole duration of
treatment duration. The study also confirmed the good
the study (3 months).
safety profile of the treatment.

Neurobion is a product from Merck Consumer Health which has helped

people to nourish and protect their nerves since it was created and was
first registered for use in Austria in 1962.
Neurobion is a combination of neurotropic B vitamins. Vitamins B1
(thiamine), B6 (pyridoxine) and B12 (cobalamin) are known to have
particularly important neurotropic roles to play in the maintenance,
nourishment and regeneration of nerves2,3, more specifically in
neurotransmitter synthesis, myelin synthesis and nerve membrane function.
In particular neurotropic B vitamins have an important role in nourishing,

compromised nerve health for example peripheral neuropathy.

Neurobion tablets contribute to nerve health and help provide relief for

vitamin B deficiency).
Neurobionis available on prescription/OTC (adapt based on country).

1 Head 2006, Peripheral Neuropathy: Pathogenic Mechanisms and Alternative Therapies, Alternative Medicine Review,
Volume 11, Number 4
2 Jolivalt et all, 2009, B vitamins alleviate indices of neuropathic pain in diabetic rats, Eur J Pharmacol, 10;612(1-3):41-7

3 Becker et all 1990, A contribution to the scientific assessment of degenerative and regenerative processes in peripheral
nerve fibers, Neurochirurgia

10
 3. Clinical study summary

The presentations can be used with the Sales Forces to provide them
with condensed and to-the-point information. These slides would be best
Guidance leveraged during a discussion (e.g. reviewed together by sales force and an
HCP) and/or relevant media outlets (e.g. sent via email as a file to view
on mobile device or desktop computer).

Summary deck currently under Zinc review

Summary deck currently under Zinc review

11
 c. Sustain assets for HCPs
4. Animated infographic

The infographic can be shared during a discussion (e.g. reviewed together by

Guidance sales force and an HCP) or as an animation (e.g. sent via email as a file to view
on mobile or desktop computer).

Increased Extreme sensitivity Pin and Reduced sensitivity Reduced sense

sensitivity to touch Sharp pain Burning pain Loss of sensation Numbness Muscle weakness
to pain needles to pain to touch

CAUSES AND SYMPTOMS OF CAUSES AND SYMPTOMS OF

NEUROPATHY ARE DIVERSE Positive symptoms NEUROPATHY ARE DIVERSE Negative symptoms

12
 NEW RESEARCH:
NON-INTERVENTIONAL CLINICAL STUDY
STUDY OBJECTIVE
Evaluate the efficacy of a fixed dose neurotropic B vitamins combination
in peripheral neuropathy of different etiologies.

STUDY DESIGN
12 weeks non-interventional clinical study with 411 peripheral neuropathy
patients
Different peripheral neuropathy etiologies included – this makes the
study special!

THE ELIGIBLE SUBJECTS

RECEIVED
Fixed dose of neurotropic IMPACT OF TREATMENT
B vitamins combination ON PN SUFFERERS’ SYMPTOMS (TSS)
(B1-100mg; B6-100mg and B12-5mg)

7
7
TOTAL SYMPTOM
SCORE (TSS)
Significant IMPROVEMENT of TSS has 6
TOTAL SYMPTOM
SCORE (TSS)
THE EFFECT INCREASES EVEN MORE AT 30, 60 AND
6
been achieved already AFTER 14 DAYS. 90 DAYS. LONGER TREATMENT DURATION SHOWS A
Significant IMPROVEMENT HIGHER BENEFIT FOR THE PATIENT.
5
5.451±2.0365 of TSS has been achieved
5
5.451±2.0365 already AFTER 14 DAYS.

NEW RESEARCH:
4
4 4.358±1,9148
4.358±1,9148 NUMBNESS 2.020±1.2808
3
NUMBNESS
3

PARESTHESIA
NON-INTERVENTIONAL 2
PARESTHESIA
3.551±1.6919

2.786±1.4801

CLINICAL STUDY
2

STABBING PAIN
1
STABBING PAIN
OUTCOME
1
BURNING PAIN
0
0 BURNING PAIN
VISIT 1 VISIT 2 (14 DAYS) VISIT 3 (30 DAYS) VISIT 4 (60 DAYS) VISIT 5 (90 DAYS)
VISIT 1 VISIT 2 (14 DAYS) Baseline
Baseline

13
 KEY TAKE OUT

OVERALL GOOD TREATMENT TOLERANCE

DURATION PROFILE
SAFETY PROFILE
OBSERVED AMONG THE TREATMENT
TREATED PATIENTS FOR EFFICACY

THE WHOLE DURATION

OF THE STUDY

TREATMENT TREATMENT
EFFICACY DURATION
A treatment with An IMPROVEMENT after 2 WEEKS OF
NEUROTROPIC B VITAMINS TREATMENT has been observed. The
COMBINATION has proven benefits IMPROVEMENT IN SYMPTOMS FURTHER
on all symptoms of peripheral INCREASES WITH TIME
neuropathy observed in
the non-interventional study –
independently from the etiology.

TOLERANCE
PROFILE
®

A long term treatment can be

recommended as it has shown a GOOD
TOLERANCE profile over the whole
duration of the study (3 months).

14
 5. Quote cards from the study investigators

You will find hereafter questions we haves asked to the study investigators
and the quote cards recapping some of the benefits of peripheral neuropathy
treatment. The answers need to be submitted for local approval.
Guidance Please note that these quotes cannot be used in a branded environment!
The quote cards can be used unbranded on a website or in a presentation for
sales force; the full questionnaire can be shared directly with sales force who
can share with HCPs and leave it behind.

Non-interventional clinical study on the benefits of a treatment

of peripheral neuropathy with different etiologies with a combination of
neurotropic B vitamins
Interview - Questionnaire for Dr. Luthy (Manfaluthy Hakim MD, PhD) /
Dr. Pinzon (Rizaldy Pinzon, MD, PhD)

QUESTION 1: What was the objective of the study?

ANSWER: We wanted to assess the improvement of the symptoms of peripheral neuropathy (PN), per
total symptom score (TSS) with a treatment by a combination of neurotropic B vitamins.
Another objective of the study was to evaluate when the treatment starts to show an effect and whether
longer treatment duration shows better impact for patients. Finally, we also wanted to evaluate the safety
of the treatment.

QUESTION 2: How was the study designed?

ANSWER: Two key factors have lead us in the design of the study: firstly, we wanted to assess the impact
of the treatment on all type of PN sufferers and we have therefore included sufferers from different
etiologies. Secondly, we wanted to see the treatment efficacy in conditions as close as possible to reality
and have therefore administrated the treatment as it is prescribed by physicians in their normal practice.

QUESTION 3: Why was this study different from some others?

ANSWER: We have selected patients with peripheral neuropathy from different etiologies. Majority of the
studies conducted up to now were focusing on one etiology only, mainly diabetic neuropathy. In the case
of this recent study we can generalise the outcomes for neuropathy sufferers of various etiologies - which
represents a real progress for sufferers and an excellent tool for the physician.

QUESTION 4: What were the main outcomes of this new study?

ANSWER: We have observed unequivocal results when it comes to the benefits of the treatment for
patients: it appears that the combination of vitamin B1 (100mg), B6 (100mg) and B12 (5000μg) with
Neurobion Forte was effective to significantly relieve the symptoms in patients suffering from mild or
moderate peripheral neuropathy, independently from the etiology.

15
QUESTION 5: Are the study outcomes of relevance for all peripheral neuropathy sufferers?
ANSWER: Absolutely. The study was conducted among more than 400 peripheral neuropathy sufferers,
with the recruitment of this high sample size, we have got a picture of the neuropathies per the
prevalence in the population. The relief was observed in patients from all etiologies. Therefore, we can
conclude that the study outcome would be of relevance for all peripheral neuropathy sufferers.

QUESTION 6: Which peripheral neuropathy symptoms were observed in the study?

ANSWER: Peripheral neuropathy can manifest itself through a variety of symptoms. In the study the
four main positive sensory neuropathic symptoms of TSS were lancinating / stabbing pain, burning pain,
paraesthesia and numbness.

QUESTION 7: How did the symptoms evolve for the observed patients?
ANSWER: We have observed a reduction in TSS within 14 days of treatment – this reduction gradually
increased significantly as the study drug treatment continued. Additionally, the clinically significant mean
reduction in TSS was observed in all subgroups under study (e.g. various etiologies).

QUESTION 8: What conclusions are you drawing with regards to the efficacy of a combination of
neurotropic B vitamins treatment for patients suffering from peripheral neuropathy?
ANSWER: Based on the outcome of this non-interventional study, I can confirm that a treatment
with a combination of neurotropic B vitamins is beneficial in relieving the symptoms for peripheral
neuropathy sufferers with different etiologies. Additionally, the impact was further improved with longer
treatment duration starting at 14 days, and increasing via 30 days, 60 days and 90 days.

QUESTION 9: What conclusions are you drawing with regards to the efficacy of a long-term
treatment with a combination of neurotropic B vitamins for patients suffering from peripheral
neuropathy?
ANSWER: Peripheral neuropathy is a chronic disease in most cases, so the treatment should be
undertaken long term. We wanted to investigate in the study the effect increasing over time. The study
lasted for 12 weeks and the relief brought by the treatment was continuously increasing. We can
therefore conclude that a longer treatment period achieves even more relief with patients.

QUESTION 10: What are the conclusions of the study with regards to tolerance to the treatment?
ANSWER: The conclusions are very positive: the treatment with a combination of neurotropic B vitamins
has shown a good tolerance profile over the whole duration of the study. This is important in my view,
especially as it looks like a longer treatment provides more relief to the patients – for longer a good
tolerance profile is even more crucial.

16
 NerveCareForum
Dr. Pinzon
I can confirm that a treatment with a
combination of neurotropic B vitamins
is beneficial in relieving the symptoms
observed in the study for peripheral
neuropathy sufferers with
different etiologies.
NerveCareForum
Dr. Luthy
In the case of this recent study we can
generalise the outcomes for neuropathy
sufferers of various etiologies - which
represents a real progress for
sufferers and an excellent tool
for the physician.
Dr. Pinzon NerveCareForum
Peripheral neuropathy can manifest itself
through a variety of symptoms such as stabbing
pain, burning pain, parasthesia and numbness.
Treatment with a combination of neurotropic B
vitamins is beneficial in relieving the
symptoms for peripheral neuropathy
sufferers with different
etiologies.
Dr. Luthy NerveCareForum
The combination of vitamin B1 (100mg), B6
(100mg) and B12 (5000μg) with Neurobion
Forte was effective to significantly relieve the
symptoms in patients suffering from mild
or moderate peripheral neuropathy,
independently from the
etiology.
NerveCareForum
Dr. Pinzon
Peripheral neuropathy is a chronic
disease in most cases, so the treatment
should be applied on long term. We can
conclude that a longer treatment with
Neurobion Forte achieves even
more relief with patients.
17
d. Equip Sales team
6. Clinical study advertorial

The following advertorial can be adapted by countries as paid educational

Guidance
advertising (paid medical information) in HCP media, both off line and online.

New non-interventional clinical study¹

DEMONSTRATES successful treatment
of peripheral neuropathy with a combination
of neurotropic B vitamins (Neurobion Forte)
independently from the etiology
NERVES The nervous system allows us to perceive, comprehend, and respond to the world
around us. It coordinates voluntary actions like walking and involuntary actions like breathing
and swallowing.
PERIPHERAL NEUROPATHY

Neuropathy can cause various body discomforts, such as tingling, increased or decreased
sensitivity, to vibration, hot or cold, numbness, muscle weakness and even burning pain.
NON-INTERVENTIONAL CLINICAL STUDY INVESTIGATING PERIPHERAL NEUROPATHY
WITH DIFFERENT ETIOLOGIES CONFIRMS THE BENEFITS OF A UNIQUE TREATMENT
FOR ALL. A new clinical study has brought a major step forward for our nerve health,
regardless of the cause of peripheral neuropathy.

It appears from the non-interventional clinical study that

the combination of vitamin B1 (100mg), B6 (100mg)

significantly relieve symptoms (observed in the study)

(as measured by TSS).

Long term benefit

Study Results: Indeed, the clinical symptoms of Peripheral
Neuropathy have shown significant
the non-interventional improvement as of visit 2 (14 days after
clinical study demonstrated start of treatment). Additionally, the impact
successful treatment of was further improved with longer treatment
PERIPHERAL NEUROPATHY duration at 30 days, 60 days and 90 days:
with a combination longer treatment duration shows a higher
of neurotropic B vitamins benefit for the patient.

Safety profile
Finally, it is equally important to note that the treatment
with a combination of neurotropic B vitamins
(Neurobion Forte) has also shown a good tolerance profile
over the whole duration of the study (3 months)

The 12 weeks prospective non-interventional clinical study (add published reference, when available) was
conducted in Indonesia and has involved 411 patients (297 female and 114 male), between 18 and 65 years,
with peripheral neuropathy symptoms. Importantly, the study methodology involved patients from multiple
CLINICAL STUDY etiologies, such as diabetes, carpal tunnel syndrome as well as idiopathic PN and others. It is all the more
important to highlight this point that there is only a very limited number of clinical studies done on PN
DESIGN: from multiple etiologies. The eligible subjects received Neurobion Forte (combination of vitamin B1-100mg;
vitamin B6-100mg and vitamin B12-5000μg) orally once daily after meals as prescribed by physicians in
their normal practice.

NEUROBION FORTE is a combination of neurotropic B vitamins. Vitamins B1 (thiamine), B6 (pyridoxine)

and B12 (cobalamin) are known to have particularly important neurotropic roles to play in the maintenance,
nourishment and regeneration of nerves²,³, more specifically in neurotransmitter synthesis, myelin
synthesis and nerve membrane function.

1 Management of peripheral neuropathy symptoms with a fixed dose combination of high dose vitamin B1, B6 and B12:
A 12 week prospective non-interventional study in Indonesia, Asian Journal of Medical Sciences, January 2018.
2 Jolivalt et all, 2009, B vitamins alleviate indices of neuropathic pain in diabetic rats, Eur J Pharmacol,
10;612(1-3):41-73.
3 Becker et all 1990, A contribution to the scientific assessment of degenerative and
regenerative processes in peripheral nerve fibers, Neurochirurgia.

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 7. Clinical study specific Q&A

The following questions and answers can be adapted locally to answer

Guidance questions from HCPs regarding the clinical study. The Q&A should be also
shared with the sales team for training purposes.

Question
What is this new study
I heard/read about?
Answer
Dear [Name], A clinical observational study has been conducted, involving
more than 400 patients, suffering from peripheral neuropathy due to
different causes. For all of them the treatment has proved to be beneficial,
with long term treatment seeing even better outcomes with longer intake.
For more information on this study check our site [LINK TO PAGE]
Best wishes, NEUROBION® team

How do I know that
the outcome of the study
applies to me?
Dear [Name], The observational clinical study has involved more than
400 patients, suffering from peripheral neuropathy due to different causes.
For all of them the treatment has proved to be beneficial, which proves that
the treatment is beneficial for different peripheral neuropathy patients.
If you would like to get more information about your personal situation,
please contact your doctor.
Best wishes, NEUROBION® team

Dear [Name], The observational clinical study has involved more than
400 patients, suffering from peripheral neuropathy due to different causes.
The causes for neuropathy in this study were diabetes, carpal tunnel
Who were involved
syndrome, idiopathic, which means the cause of their neuropathy was
in the study?
unknown and others.
For more information on this study check our site [LINK TO PAGE]
Best wishes, NEUROBION® team

Dear [Name], The observational clinical study has involved more than
400 patients, suffering from peripheral neuropathy due to different causes.
For all of them the treatment has proved to be beneficial, with long term
What are the conclusions
treatment seeing even better outcomes. Additionally, the study treatment
of the study?
was well tolerated over the whole study duration of three months.
For more information on this study check our site [LINK TO PAGE]
Best wishes, NEUROBION® team

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 Question
Why do you say that
this study is different from
some others?
Can I trust the study
outcome? Has it been
sponsored by Neurobion?
What do you mean by
'good tolerance profile'?
Which symptoms were
tested in the study?
Is this study works for any
Neurobion formulation?
Answer
Dear [Name], The observational clinical study has involved more than
400 patients, suffering from peripheral neuropathy due to different causes.
There is a very limited number of studies conducted on a patient population
with so diverse causes of neuropathy, which makes this study different.
Most research studies available today focus on diabetic peripheral neuropathy.
For more information on this study check our site [LINK TO PAGE]
Best wishes, NEUROBION® team
Dear [Name], The observational clinical study has involved more than
400 patients in eight different study centers; the study was conducted under
the review of independent investigators and the methodology was per all
regulations and ethical guidelines for state of the art clinical studies.
Best wishes, NEUROBION® team
Dear [Name], For the whole duration of the non-interventional clinical study
only very limited adverse events were observed (no serious adverse event),
which classifies the treatment as having a good safety profile.
For more information on this study check our site [LINK TO PAGE]
Best wishes, NEUROBION® team
Dear [Name], The observational clinical study was assessing the impact of
a Neurobion treatment primarily on symptoms such as burning pain, stabbing
pain, paraesthesia and numbness. These are among the most frequent
symptoms of peripheral neuropathy.
For more information on this study check our site [LINK TO PAGE]
Best wishes, NEUROBION® team
Dear [Name], The observational clinical study was assessing the impact of
a Neurobion Forte treatment. Whilst we cannot extrapolate based on the
study results on the efficacy of other Neurobion treatments it is important
to note that Neurobion is a combination of neurotropic B vitamins which
are known to have a particularly important role to play in the maintenance,
nourishment and regeneration of nerves.
For more information check our site [LINK TO PAGE]
Best wishes, NEUROBION® team
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3. Evaluation guide
The key objectives of this toolbox are to disseminate the outcome of the new Nenoin study to engage.
In this context, we wanted to provide you with some guidance on what does success look like in terms of
using this toolbox.

1. Content and assets from the toolbox to reveal the study outcome
The first assets from this toolbox are suitable to reveal the outcome of the new Nenoin study.
What does success look like: after reviewing the content locally, you select the material which you
leverage in a medical symposium and directly through the media (via press release).

2. Content and assets from the toolbox to sustain HCP interest and own study
outcome
Some toolbox assets are fitted to continue to generate interest, for HCPs who are aware of the study
outcome and those who are not. Some assets, such as the animation, are especially designed for being
self explanatory for HCPs previously not exposed to the study.
What does success look like: after reviewing the content locally, you select the assets which you would
like to leverage with HCPs (e.g. investigator quotes, animated infographic) and disseminate these with your
local HCPs to build the reputation of the Neurobion brand.

3. Continue to spread the news among HCPs through equip Sales team
Several assets from the toolbox are extremely suitable for HCP training purposes, for example the Medical
training slide kit or the study specific Q&A.
What does success look like: after reviewing the content locally, you equip your sales force so that
they can engage the HCPs around these study results, sharing the great news that a recent study has
1) evidenced the benefit for sufferers of the Neurobion Forte treatment 2) proved the benefits of long
treatment 3) confirmed the safety profile.

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