CYCLE BRIEF - ZELMAC®

Dear Zelmac® Team,

Welcome to the most exciting brain change!

This is going to be a paradigm shift of note for all of us in the Novartis. You will receive many tools to assist you to sell Zelmac® well into 2005.

I have 3 requests:

1 Please make sure you use the material as set out for you and do not deviate from the Zelmac® strategy and the key messages. Consistency in message transfer is vital for establishing and growing a brand.

2. Do not underestimate the competition although old and relatively inactive, changing to a new approach of treatment will be difficult for doctors , pharmacists and patients alike, the issue of the cost will come up in many of your calls. My request is that you accept this and use it as an opportunity to make sure that you prioritise pharmacies like you have never before. Please make this mind-shift and make sure you keep your finger on the pulse at pharmacy level. The role of the pharmacist to convince the patient to pay for Zelmac® out of pocket is vital.

3. Please do not assume anything. The frontier selling is awesome to assist you with selling Zelmac®. Your doctors are going to all be at different levels of understanding, and diagnosing IBS. Once a doctor is well educated on IBS and is confident in making the C-IBS diagnosis using the ROME II criteria, he will understand how Zelmac® fits into the management of a C-IBS patient.

I wish you all the best for the change ahead both at work and in your personal life. The following quote from Mark Twain sums it up beautifully:

Dance like no one is watching.Sing like no one is listening.Love like you have never been hurt.Live like its heaven on earth.

Wishing you all the best with Zelmac® with the exciting PF perspective!

Regards

Hana Arjan

DOCTOR SALES AID

This cycle brief will provide you with the rationale for each page. i.e. why is this page even in the sales aid?

You will also be provided with key messages per page. The sales aid is designed in landscape and each double page spread works together. PLEASE DO NOT FOLD THE DETAIL AID IN HALF.

Pages 1 and 2 C-IBS Patient Profile

Why these pages?

It is critical for any drug that the doctor knows how to identify the right patient for the drug you are selling. It is therefore vital that we continue to profile the patient so he knows how to identify her.

As you will see from the patient profile and from what we know about IBS, many of these factors will only be uncovered if the doctor asks the right questions. Remember that diagnosing IBS using the Rome II criteria is a diagnosis based on symptoms, and he will only uncover these symptoms by talking to the patient.

The patient profile has been divided into sections. These sections will assist the doctor with the type of questions he asks.

Page 1

Who is she?

Female : male ratio 2 :1 so the majority of his IBS patients will be female, and generally in good health.

Attacks are severe:

An IBS patient would not be at the doctor if the attacks were not severe and did not impact on her life ie. her symptoms are legitimate. This section also re-iterates that IBS symptoms wax and wane, and some days are worse than others.

How does she present:

The A, B, C’s are the 3 predominant symptoms of C-IBS but are not the only symptoms she has. Also remind the doctor that the patient may not necessarily complain of all 3 on initial questioning. The doctor will need to probe to uncover all her symptoms. Remind the doctor at this stage that according to the Rome II criteria, she has to have abdominal pain with a change in bowel habit ie. Constipation, to make a positive C-IBS diagnosis.

For how long has she experienced these symptoms?

IBS is chronic. The doctor needs to uncover that she has a history of these symptoms. Remind the doctor that the Rome II criteria looks at (no less than) 12 weeks (need not be consecutive) in the preceeding 12 months.

A patient who has these symptoms for only a week for example, needs to be investigated further for the cause of the symptoms.

A, B, C – it is vital that you re-iterate that Zelmac® is for C-IBS and that is why the 3 predominant symptoms are so vital. This whole detail aid is designed to re-iterate the A, B, C’s.

Page 2:

Her symptoms have an impact on her life and affect various facets of her life.

This enables you to tie this back to the fact that her attacks are severe. Symptoms that affect her productivity at work, how she views herself and the lifestyle changes she makes with all this impacting on her relationships are not to be taken lightly, and have a huge impact on her quality of life.

Key Message:

The predominant symptoms of a C-IBS patient are abdominal pain, bloating and constipation. These symptoms wax and wane and affect all aspects of her life, leading to decreased quality of life.

Page 3: Impact of IBS

Why this page?

Many doctors do not view IBS as a legitimate condition. They will fall into the “doesn’t recognise” in the A – B shift. This page will assist you to highlight that IBS is prevalent: they should be seeing it in their practice and it takes up a large portion of both a GP’s and Gastroenterologists practice. There are also many costs involved in managing IBS: some costs are direct and are of a monetary value, but the most important cost for a patient is the impact of IBS on her quality of life.

Prevalence

Ask your doctor how many patients he has in his practice. Then apply the prevalence of 10 – 20% to the number of patients in his practice to assist him in ascertaining how many potential IBS patients he has in his practice.

Consultations:

Use the 12% primary care consultation figure to re-iterate that IBS is common and apply this to his practice e.g. if he sees 30 patients per day he is seeing 3 potential IBS patients per day. This should grab his attention and highlight to him that he is missing potential IBS patients. This type of discussion will also emphasise that IBS is a legitimate and common condition.

Costs:

Use the direct costs section to get him thinking about patients he is seeing frequently and Rx products for, as well as those patients he has even hospitalised for diagnostic procedures.

The indirect costs are relevant as he may find that some patients who see him for the first time may be taking OTC products to relieve their symptoms.

The most important cost (intangible) is the impact of IBS on the patients’ quality of life.

This leads you into the next 3 pages i.e. how does IBS impact on the patients’ quality of life.

Key Message:

The impact of IBS is high as it is a prevalent condition which takes up much of the doctors consultation time, and the cost of IBS is measured in monetary terms as well as an impact of the patients quality of life.

Page 4: Impact on QOL versus other chronic or episodic conditions

Why this page?

This page will assist you with the doctor who falls into the “doesn’t treat” category in the A – B shift. If you talk to any doctor he will agree with you that asthma and migraine are common and have a huge impact on the sufferers’ quality of life. Both migraine and asthma are viewed as chronic, episodic conditions. So is IBS. The awesome fact about IBS is that the impact of IBS on QoL is often more than that seen with asthma and migraine sufferers. Discussing this with your doctor who doesn’t view IBS as serious enough to treat will highlight the impact of IBS on the patients’ quality of life and start making him think that he should treat the IBS patients. This will help legitimise IBS.

How to describe the graph

This graph is devised using the concept of patient – based outcome assessments ie. a health–related quality of life (HRQOL) assessment This type of assessment is becoming increasingly important due to the fact that objective clinical end points in functional GI disorders are often unavailable.

HRQOL assessments address patients’ perceptions of aspects of their life that are affected by disease and its treatment. It is multidimensional, comprising physical, social, psychological functioning and well-being.

This trial uses the Medical Outcomes Study 36–item short-form Health Survey (SF-36). This has been widely used in primary care and chronic disease populations. It consists of 8 sections that evaluate various aspects of physical and psychological functioning or well-being.

1. Physical functioning: relates to self-care and physical limitations in performing rigorous or moderately rigorous daily activities.

2. Physical role: measures problems with work or other daily activities associated with physical health.

3. Bodily pain: measures the intensity of pain and the extent to which it interferes with normal activities.

4. General health: assesses the patients perceptions of his or her current and future health.

5. Vitality: evaluates energy level and fatigue.6. Social functioning: measures quantity and quality of patients

social activities.7. Emotional role: addresses the impact of emotional problems on

daily activities.8. Mental health: concerns anxiety, depression and psychological

well-being.

How to read the graph

Each section has a possible range from 0 to 100, with higher scores indicating better health. Therefore, the lower the bar graph the worse the quality of life. Note that IBS has the greatest impact on quality of life for all the domains other than the physical functioning domain.

The total number of IBS patients interviewed with the SF-36 assessment was 1 636.

The 2 statements below the graph are NB in re-iterating that IBS is a chronic condition and that IBS patients do suffer – this links back to the statement in the patient profile.

Key Message:

The impact of IBS on QOL versus other common chronic episodicconditions is often worse than the other conditions. It is therefore vital that the IBS patients are treated, so that their QOL can be improved.

Page 5: Impact on QOL – the patients perspective

Why this page?

This page will also assist you with the doctor who falls into the “doesn’t recognise” and “doesn’t treat” category in the A-B shift. The previous page compared the impact of IBS on QOL versus other chronic conditions. This page provides you with the impact of IBS in over 40,000 people – this is the IBS Truth Survey,

The 41 984 people interviewed, were asked about the extent to which their general state of health affected their lives. This graph shows the 13 specific factors which affected their lifestyles. In all of these categories, IBS sufferers were more likely to report problems than non-sufferers.

Overall, 78% of IBS sufferers reported that their general state of health affected their lives, compared with 60% of those who did not have IBS.

Please remember that one factor is not necessarily more important than another. Also, each person will have a different combination of factors which they mentioned. The diversity of the factors is NB and really emphasises the extent of how IBS affects a person’s QOL.

Remember that non-IBS sufferers will have these factors influenced by other things in their life eg. sleep could be affected by a baby in the house, and diet could be affected by working long hours and having to rely on fast food.

Key Message:

IBS has a serious impact on patient’s daily activities and QOL.

Page 6 : GI Symptoms in C-IBS sufferers

Why this page?

The previous 3 pages on the impact of IBS on QOL encompass all types of IBS.

This page specifically looks at the GI symptoms that a C-IBS patient suffers from. This page will assist you with those doctors who do not recognise the C-IBS patient or who say that they just don’t see the patients or are unsure of how to diagnose the C-IBS patient. This can also be linked to the patient profile pages.

This information shows that C-IBS sufferers do not have a subtle alteration in bowel habits as these factors have an incidence of less than 10% in non C-IBS sufferers (this is the usual cycle changes we all have in our bowel habits).

The graph is divided into A, B, and C as these are the predominant symptoms we discussed in the patient profile.

This graph is NB to again re-iterate to the doctor that the patient could use other terms for describing that she is bloated or has constipation. This again highlights the importance of the doctor asking questions and discussing her symptoms with her.

Remember that there are 2 sections to the Rome II criteria and the second section discusses symptoms that are not essential for diagnosis but increase confidence in making the diagnosis. The star guide will assist you in discussing the ROME II criteria with the doctors to assist him in making the C-IBS diagnosis. This again re-iterates that the diagnosis of C-IBS is a symptomatic diagnosis.

Key Message:

C-IBS patients report a high incidence of abdominal pain, bloating and constipation as their predominant symptoms.

Page 7: Traditional therapies

Why this page?

This page will assist you with those doctors who do recognise and treat C-IBS, but are treating narrowly with traditional therapies, and have not yet made the shift to Zelmac® as the preferred therapy.

This page is divided into the A, B, and C’s and the drug classes used for each symptom are listed. The right hand column explains how the traditional therapies do not meet the need and often exacerbate the predominant symptoms of C-IBS.

Please make sure you go through each of the 3 sections and cross discuss how the use of some therapies for one symptom eg. abdominal pain can exacerbate another symptom ie. constipation.

Key Message:

Traditional therapies do not meet the need and only treat individual symptoms. The traditional therapies also exacerbate other symptoms and do not address the underlying cause of C-IBS.

Page 8 : What would be the ideal C-IBS

Why this page?

This page is for the doctor who treats narrowly and who you have convinced that his traditional therapies are not meeting the need. This page sets you up to sell Zelmac® as the only product that meets the need.

The 3 factors listed here are cited in the literature.

1. addresses the underlying cause : brain-gut axis.2. global multisymptom relief : SGA of relief which looks at relief

of the abdominal pain, altered bowel movement and overall well being.

4. specific ABC symptom relief ÷ multisymptom relief which none ofthe traditional therapies provide.

Key Message:

Zelmac is the only treatment available that meets all 3 criteria and provides multisymptom relief of C-IBS.

Pages 9 and 10 : First in a new class

Why these pages?

Once you have convinced a doctor that IBS is a common and legitimate condition that has a huge impact on a patient’s quality of life, and that the traditional therapies do not meet the need, this page and those that follow give you the information to sell how Zelmac® meets the 3 criteria of the ideal C-IBS treatment.

These 2 pages have to be used together. The left page explains the underlying cause ie. brain-gut axis and that serotonin is the mediator between the CNS and ENS. Zelmac® is the only selective 5HT4 agonist that works on the brain-gut axis and therefore works in 3 ways to normalise the GI function- remember that November research shows that we have not achieved our goal of distinguishing Zelmac® from traditional therapies. Left hand page gives the problem and the right hand page gives the solution as to the 3 ways that Zelmac® works to address the problem.

Key Message:

Zelmac is the only treatment that provides multisymptom relief of C-IBS by working in 3 ways to address the underlying cause.

Page 11 and 12: Multisymptom relief Why this page?

These 2 pages show that Zelmac® provides global multisymptom relief and provides specific ABC symptom relief. These are 2 of the 3 factors of the ideal C-IBS treatment.

Clinical response graph:

This Muller Lisner trial was in your launch detail aid. This trial was designed according to the Rome II criteria and assesses SGA of relief over a 12 week period. So what? SGA of relief takes the 3 central factors of IBS into account ie. abdominal pain/discomfort, altered bowel function and overall well being. The overall well being factor is important considering the high impact of IBS on QOL.

The graph shows that Zelmac® provides rapid and sustained multisymptom relief throughout the treatment period. The SGA of relief is significantly improved within the first week. Don’t be ashamed of the 67% clinical response – this is realistic as we know that not all patients will respond to Zelmac® and no one really understands why.

Key Message:

Zelmac provides rapid and sustained multisymptom relief of the symptoms with C-IBS

Page 13: Multisymptom relief

Why this page?

Abdominal pain is the most frequently reported symptom and remember that it is used as part of the ROME II criteria in diagnosing IBS. Therefore, showing a significant reduction in abdominal pain with Zelmac® is a great advantage.

How to read this graph:

The more the daily abdominal pain score moves away from the baseline ie. 0 and becomes more negative, the better the reduction in abdominal pain.

Note that Zelmac® results in a significant reduction in abdominal pain and this effect is rapid and sustained.

Key Message:

Zelmac provides a significantly rapid and sustained relief of abdominal pain.

Page 14 : Multisymptom relief

Why this page?

This page describes how Zelmac® meets the third criteria of the ideal C-IBS treatment ie. provides specific A, B, C symptom relief.

Zelmac® significantly improves abdominal pain, significantly reduces bloating, and significantly improves the number of bowel movements and decreases stool consistency, thereby relieving constipation.

Key Message:

Zelmac is the only treatment available that provides multisymptom relief of the ABC’s of C-IBS, leading to improved QOL.

Page 15: Zelmac® C-IBS

Why this page?

This is your summary page of how Zelmac® has all the desired characteristics to be incorporated into the management of C-IBS.

Use this page to re-iterate how Zelmac® is different from traditional therapies and meets the 3 factors of the ideal C-IBS treatment:

1. addresses the underlying cause by working on the brain-gut axis2. provides global multisymptom relief which is rapid and sustained3. provides specific A,B,C relief by significantly reducing abdominal

pain, bloating and constipation.

Page 16: Zelmac® for C-IBS

Why this page?

This is your dosage page. It is vital that the Zelmac® RX is written for a month so that the patient will experience all the benefits of Zelmac® and experience improved QOL. Remember that we do not have any data for a treatment period of less than one month.

Key Message:

Zelmac is the only treatment available that provides multisymptom relief of C-IBS by addressing the underlying cause