A new phase of dynamic growth
`
`Annual Report 2006
`
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`

`

`Actelion at a glance
`Actelion Ltd, founded in December 1997, is a biopharmaceutical company with corporate
`headquarters in Allschwil/Basel, Switzerland, that focuses on the discovery, development
`and commercialization of innovative treatments to serve high unmet medical needs.
`
`Actelion’s flagship product, Tracleer®, an orally available dual endothelin receptor antago-
`nist, has been approved as a therapy for pulmonary arterial hypertension (PAH), a chronic,
`life-threatening disorder that severely compromises the functions of the lungs and heart.
`Ventavis®, the only inhalable PAH therapy in the United States, was acquired in 2006.
`Zavesca®, in-licensed from Oxford GlycoSciences, is the only approved oral treatment for
`type 1 Gaucher disease, a rare debilitating metabolic disorder.
`
`In 2006, Actelion was evaluating 8 compounds in various phases of clinical development
`and pursuing 25 projects in drug discovery that target cardiovascular, cardiopulmonary,
`immunological, and infectious diseases, as well as metabolic and central nervous system
`disorders.
`
`The over 1,200 Actelion employees strive to combine the innovation, entrepreneurial spirit
`and flexibility of a biotech firm with the financial, risk management, regulatory and commer-
`cial discipline of a large pharmaceutical company. Actelion’s strategy of maintaining max-
`imum value from scientific innovation is complemented by ongoing alliances with Merck in
`orally available renin inhibitors for cardiovascular indications and with Roche in S1P1 ago-
`nism in autoimmune disorders.
`
`Actelion has set a rapid pace in achieving commercial success. The first substantial prod-
`uct sales were generated during 2002, followed by a full-year net income in 2004. Actelion
`posted sales of CHF 945.7 million in 2006. Operating income was CHF 268.2 million and net
`income CHF 241.1 million.
`
`Total revenues
`EBIT
`Net profit
`EPS non-diluted
`Cash from operations
`Net equity
`Employees (FTE equivalent)
`
`2006
`945.7
`268.2
`241.1
`10.64
`352.8
`578.1
`1,252
`
`2005
`663.6
`152.3
`125.5
`5.62
`138.4
`321.7
`1,028
`
`2004
`471.9
`85.6
`87.2
`3.96
`91.7
`158.1
`854
`
`2003
`307.5
`(1.7)
`(9.9)
`(0.46)
`38.3
`54.4
`660
`
`2002
`132.4
`(32.0)
`(52.1)
`(2.45)
`(35.8)
`50.3
`412
`
`CHF million except per share and employee data
`Includes discontinued operations
`
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`

`

`Content
`
`Letter from the Chairman
`
`Interview with the CEO
`
`Business Highlights
`
`Patient Stories
`
`Clinical Development
`
`Drug Discovery
`
`Inside Story
`
`People
`
`Letter from the CFO
`
`Corporate Governance
`
`Consolidated Financial Statements
`
`Holding Company Statements
`
`Shareholder Information
`
`Contacts
`
`04
`
`06
`
`11
`
`14
`
`17
`
`27
`
`30
`
`33
`
`34
`
`38
`
`47
`
`70
`
`76
`
`78
`
`Actelion Annual Report 2006
`Discovery
`Inside Story
`
`Patient Stories
`Business Highlights
`CEO Interview
`Chairman’s Letter
`People
`CFO’s Letter
`Corporate Governance
`Financial Statements
`
`Clinical Development
`Shareholder Information
`
`Drug
`Contacts
`
`03
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`

`

`Robert E. Cawthorn
`Chairman of the Board
`
`Letter from the Chairman
`
`Leveraging our unique assets to drive the next
`cycle of growth
`
`In 2006, we achieved another year of outstanding business results, while simultaneously
`laying the foundation for future growth with key infrastructure investments, organizational
`expansion, substantial progress in pivotal clinical trials, a groundbreaking co-development
`deal and the largest acquisition in our history.
`
`Actelion’s net revenue increased 43% over 2005 to a total of CHF 945.7 million, driven by the
`strong momentum of Tracleer® in pulmonary arterial hypertension (PAH). Operating income
`rose 76% to CHF 268.2 million, and net income increased 92% to CHF 241.1 million.
`
`In just over nine years of existence as a company, we have succeeded in launching two
`breakthrough therapies that are improving the lives of patients around the world. Our flag-
`ship product, Tracleer®, is on track to exceed one billion Swiss francs in sales by the end
`of 2007 – two years ahead of schedule. That is a truly remarkable achievement. Zavesca®,
`our innovative oral therapy for rare lipid storage diseases, posted sales of CHF 25.4 million
`in 2006 – almost doubling compared to 2005.
`
`Acquisition of CoTherix, co-development agreement with Roche
`In November 2006, we took the important step of acquiring the US-based biopharmaceuti-
`cal company CoTherix, Inc. for USD 389 million – the largest acquisition in our history. The
`excellent product fit will strengthen our leadership position in pulmonary arterial hyperten-
`sion (PAH). Ventavis® (iloprost), previously marketed by CoTherix, is the only approved
`inhalable PAH therapy in the United States. Actelion expects Ventavis® sales to make a
`substantial contribution to product revenues in 2007.
`
`“At Actelion, we are
`right at the cusp of a
`new cycle of dynamic
`growth in our evolution
`as a global biopharma-
`ceutical company.”
`
`Another highlight of 2006 was an exclusive agreement with the global pharmaceutical com-
`pany Roche to co-develop and commercialize our S1P1 agonist, a novel immunomodulator
`with possible application in a number of diseases and the potential for once-a-day oral dos-
`ing. This agreement resulted in an upfront payment of USD 75 million to Actelion in 2006,
`and foresees additional payments of up to USD 555 million for the first compound as well as
`payments for further compounds. Actelion and Roche will share equally the costs of later-
`stage development and marketing, with future product revenues shared equally as well. In
`addition, Actelion will receive royalties on marketed products.
`
`State-of-the-art R&D infrastructure, global reach in Marketing and Sales
`In addition to acquisitions and agreements, Actelion is driving growth by making the most
`of our unique assets. In 2006, we moved into a customized, state-of-the-art Research
`Center at our headquarters in Allschwil that will facilitate drug discovery. At the beginning
`of 2007, we completed our new Clinical Development Center, where we are managing the
`ongoing trials that will generate our next wave of innovative products.
`
`For a company our size, it is unique to have a successful Marketing and Sales organization
`with global reach. This has been an integral part of our company strategy from the begin-
`ning in order to retain maximum value from our products. Our agreement with Roche illus-
`trates the value of that strategy by allowing us to co-market, on an equal footing, products
`developed from our S1P1 agonist.
`
`04
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`

`

`Another key asset of Actelion is financial independence. As a profitable company with a
`strong cash-generating ability, we are masters of our own destiny. We can and must pur-
`sue those projects that we believe have the most scientific merit and impact on patients’
`quality of life. That philosophy is reflected in our passion for drug discovery and provides
`the base from which we turn innovation into value.
`
`One of the strongest pipelines in the biopharmaceutical industry
`In 2007, Actelion is aiming to pursue five Phase III clinical trials simultaneously. Our current
`growth engine, Tracleer®, is about to start Phase III trials in idiopathic pulmonary fibrosis –
`an indication that could double our current sales. Actelion-1, a potential successor drug to
`Tracleer® with many times its potency, is about to go into Phase III in the enlarged indication
`of pulmonary hypertension. Our orexin receptor antagonist, which is scheduled to enter
`Phase III in late 2007, has the potential to completely transform the treatment paradigm in
`sleep-related disorders. Our endothelin receptor antagonist clazosentan achieved the pri-
`mary endpoint of reducing cerebral vasospasm in patients with aneurismal subarachnoid
`hemorrhage, and we are now in discussions with the FDA on the methodology of a Phase III
`trial. Finally, we are planning to begin Phase III trials with tezosentan in patients undergoing
`cardiac surgery. Looking at the enormous potential of our late-stage compounds as well as
`earlier-stage projects such as our alliance with Merck to develop renin inhibitors and our
`collaboration with Roche in S1P1 agonism, it is easy to understand why Actelion’s R&D
`pipeline is the envy of companies many times our size.
`
`SOX compliance is a milestone in world-class financial standards
`In 2006, Actelion reached another important milestone in its efforts to build a world-class
`biopharmaceutical company: compliance with the rules and regulations of the US
`Sarbanes-Oxley Act of 2002, Section 404, better known as SOX.
`
`We have undertaken this effort on a voluntary basis, as only companies listed at US stock
`exchanges are required to be SOX-compliant. This is an important sign to the international
`investment community that we are committed to adhering to the most demanding financial
`and corporate governance controls that exist today.
`
`Actelion’s Strategic Plan makes our vision transparent and actionable
`At Actelion, we are right at the cusp of a new cycle of dynamic growth in our evolution as
`a global biopharmaceutical company. The key to our continued success lies in the creativ-
`ity, energy and dedication of our people.
`
`In 2006, we not only continued to implement the initiatives outlined in our Strategic Plan, but
`we also undertook a company-wide effort to ensure that all employees fully understand the
`key initiatives and priorities as well as the demands and rewards of such a growth strate-
`gy. By aligning the whole company behind our core values – innovation, results-driven
`behavior, open communication, and trust and teamwork – the talents of our people will be
`transformed into scientific innovation and business results.
`
`Robert E. Cawthorn
`Chairman of the Board
`
`Actelion Annual Report 2006
`Discovery
`Inside Story
`
`Clinical Development
`Patient Stories
`Business Highlights
`CEO Interview
`Chairman’s Letter
`People
`CFO’s Letter
`Corporate Governance
`Financial Statements
`Shareholder Information
`
`Drug
`Contacts
`
`05
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`

`

`Jean-Paul Clozel
`Chief Executive Officer
`
`Interview with the CEO
`
`“Our company culture is a compass that guides
`us in our daily business decisions”
`
`Why do you consider 2007 a “turning point” for Actelion?
`We are at a critical stage in the growth and evolution of our company. If we look back at
`our past successes and become complacent, we will remain a mid-size European biophar-
`maceutical company. If we grasp the new opportunities ahead of us and make the most of
`them, we have the potential to become the next Amgen or Genentech. Actelion has the
`necessary assets to make that leap: financial independence powered by an innovative
`product soon to exceed one billion Swiss francs in sales, a professional Marketing and
`Sales force with global reach, a pipeline that is one of the best in the industry, and newly
`built state-of-the-art R&D facilities at our headquarters. The most important asset, how-
`ever, is the energy, commitment and creativity of our people.
`
`Is that why you recently visited the Actelion affiliates around the world?
`I wanted to make sure that our employees have a strategic view of where our company
`stands today, where we can go tomorrow, and why the contribution of each individual is
`critical to getting us there. I also wanted to reinforce the role of our company culture as the
`“glue” that holds all of us together – whether it’s in Allschwil, San Francisco, Sydney or
`Tokyo.
`
`Why do you put such emphasis on face-to-face communication?
`I believe that for an employee, there is nothing more credible than having someone from
`senior management speaking to you face to face and answering your questions. That kind
`of personal and open communication is a trademark of Actelion. During my visit to our affil-
`iate in Greece, a new employee remarked that after 20 years in the pharmaceutical indus-
`try, this was the first time that he had seen a CEO in person. That speaks volumes about
`what sets us apart from other companies.
`
`“Culture is something
`that can’t be bought or
`created overnight – it is
`the unique, intangible
`quality that distinguish-
`es one company from
`another.”
`
`What were the most frequently asked questions from employees?
`Many employees wanted to know how we can grow so quickly and still keep our culture
`intact. Another frequent question addressed whether Actelion will remain an independent
`company. On the first question, I emphasized our determination to remain true to our cul-
`ture despite rapid growth. On the second, I underlined my commitment to shareholders and
`employees to preserve Actelion’s independence. The best protection against possible
`takeovers, I pointed out, is to increase the value of the company through our daily work. In
`2006, our efforts were rewarded by a 147% increase in the value of Actelion’s shares over
`the previous year.
`
`06
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`

`

`What makes company culture so important at this point in time?
`Culture is something that can’t be bought or created overnight – it is the unique, intangible
`quality that distinguishes one company from another. Actelion’s culture is built on the pil-
`lars of innovation, open communication, trust and teamwork, and achieving results. During
`this period of rapid growth, our culture helps new employees – many from larger pharma-
`ceutical companies – assimilate and contribute more effectively. Our company culture is
`also a compass that guides us in our daily business decisions. Is a potential product truly
`innovative? Does it address a real medical need? Which research approach would I
`choose if someone from my family had this particular disease? These are the kind of ques-
`tions we ask ourselves. My experience as a doctor also influences my decisions and those
`of my colleagues – patients aren’t just numbers to me; they are names and faces.
`
`Is the acquisition of the American biopharmaceutical company CoTherix in 2006 an
`example of that cultural compass?
`Absolutely. The CoTherix licensed product Ventavis® is the only inhalable therapy on the US
`market for pulmonary arterial hypertension (PAH), a disease with a medical prognosis
`worse than many forms of cancer. This therapy complements the mode of action of our flag-
`ship product Tracleer® and our pipeline compound Actelion-1 as well as strengthening our
`overall leadership position in PAH. It is a perfect fit.
`
`How is Actelion’s culture of innovation linked with value?
`Innovation without value is not sustainable. If researchers discover novel compounds and
`the company has no other option than to license them out, scientific innovation is not gen-
`erating maximum value. That is why at Actelion we decided from the beginning to develop
`our own Marketing and Sales force. Today, we are one of the few biopharmaceutical com-
`panies with a truly global reach in getting our products to the marketplace. Our strategic
`co-development and co-marketing agreement with Roche in 2006 for our S1P1 agonist
`reflects these commercial capabilities. Innovation is also linked with risk, with journeying
`into the unknown. It’s tempting to take shortcuts and go down the conventional path of “me-
`too” products, but that is not who we are as a company.
`
`Actelion’s culture of innovation is not limited to the laboratories. Finding a more efficient
`way to conduct meetings, a fresh approach to organizing a medical congress or a higher
`quality way of running a clinical trial at comparable cost to others can also be innovative
`and create value. I constantly encourage people from all parts of the company to open their
`minds and try new ways of solving problems.
`
`“It’s tempting to go
`down the conventional
`path of ‘me-too’ prod-
`ucts, but that is not
`who we are as a com-
`pany.”
`
`Actelion Annual Report 2006
`Discovery
`Inside Story
`
`Clinical Development
`Patient Stories
`Business Highlights
`CEO Interview
`Chairman’s Letter
`People
`CFO’s Letter
`Corporate Governance
`Financial Statements
`Shareholder Information
`
`Drug
`Contacts
`
`07
`
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`

`

`
`
`08
`08
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`Interview with the CEO
`
`How does Actelion’s culture need to further evolve to reach the company’s ambitious
`goals?
`We have the necessary assets and cultural values in place. What we need now is hard
`work and professional execution. That may sound rather basic, but with the products on the
`market and five upcoming Phase III clinical trials as well as a multitude of earlier trials, it is
`of vital importance. We are now just beginning to climb a huge mountain of work. The key
`to success is steady determination – one step at a time – spurred on by the knowledge that
`when we reach the top, we will have a whole new magnitude of business opportunities and
`scientific perspectives.
`
`How do you see your own role as CEO in this context?
`I see my primary role as creating the necessary conditions for success. I serve the inter-
`ests of the company by making sure that employees have the right tools to do their jobs,
`that information and ideas are shared effectively, that decision-making happens quickly
`without bureaucratic delays, and that we place the necessary resources behind our strate-
`gic priorities. I also want to energize our people by sharing my own deeply held convictions
`and enthusiasm for who we are, what we do, and how we can realize our potential. This is
`an exciting, unparalleled juncture in our young history as a company – what we make of it
`depends on each and every one of us.
`
`“My experience as a
`doctor also influences
`my decisions – patients
`aren’t just numbers to
`me; they are names
`and faces.”
`
`Actelion Annual Report 2006
`Discovery
`Inside Story
`
`Clinical Development
`Patient Stories
`Business Highlights
`CEO Interview
`Chairman’s Letter
`People
`CFO’s Letter
`Corporate Governance
`Financial Statements
`Shareholder Information
`
`Drug
`Contacts
`
`09
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`

`
`
`10
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`Business Highlights
`
`Strengthening a position of market leadership
`
`Actelion remained on a fast growth track in 2006 and continued to build on its market leader-
`ship in pulmonary arterial hypertension (PAH), with sales of CHF 898.7 million for Tracleer® –
`an increase of 42% over the previous year. Actelion’s acquisition of the American company
`CoTherix in 2006 and its licensing rights to market the only inhalable PAH therapy in the United
`States is projected to add substantial revenues in 2007, on top of robust Tracleer® sales.
`
`The strong performance of Actelion’s flagship product has been driven by an expansion of the
`Marketing and Sales force during the past two years. Customer segmentation has allowed
`key account managers to maximize this added marketing muscle, increasing the number of
`sales calls and the overall share of voice in the marketplace. A strategic reorganization in the
`Marketing and Sales force provided additional momentum. Global Medical Marketing
`Leaders now work in tandem with Global Brand Leaders to ensure aligned product position-
`ing worldwide and better integration of market demands into clinical trial design.
`
`Actelion’s commitment to expand Tracleer® into new indications where there is an unmet
`medical need will continue to broaden the company’s foundation. Based on the results of the
`BREATHE-5 study, the approved label for Tracleer® has been amended in several markets to
`include treatment for Eisenmenger’s syndrome, a severe congenital heart defect. Strong data
`from the EARLY clinical trial in mildly symptomatic pulmonary arterial hypertension (NYHA
`modified functional class II), which represents a major advance in treating patients in the first
`stages of this disease, will be submitted in spring 2007 for review by regulatory authorities for
`possible label expansion. Actelion also expects to submit clinical data from the FUTURE-1 trial,
`which shows the benefits of a special formulation of Tracleer® for children afflicted with PAH.
`
`As pulmonary arterial hypertension is still underreported and often misdiagnosed, education
`continues to be a pillar of the marketing strategy. At the World Congress of Cardiology in
`Barcelona in September 2006, Actelion launched the first-ever global PAH awareness cam-
`paign targeted at healthcare professionals. This campaign included the launch of an educa-
`tional website (www.pah-info.com) to provide the medical community with up-to-date infor-
`mation on the disease and its diagnosis.
`
`Expanded global presence and accelerated US sales with Ventavis®
`Geographic expansion was another driving force behind Actelion’s success in 2006, with
`Tracleer® now available in more than 30 countries. Some of the fastest sales growth rates
`were posted by Brazil, Eastern Europe, China and South Korea. These markets will contribute
`an increasing proportion of total revenue for Tracleer® in the coming years.
`
`The acquisition of the American company CoTherix and its licensing rights for Ventavis® (ilo-
`prost) in 2006 are considerably strengthening Actelion’s franchise in pulmonary arterial hyper-
`tension in the United States. Ventavis®, the only inhalable PAH therapy on the US market, has
`a mode of action that complements the mechanism of Tracleer® as a dual endothelin recep-
`tor antagonist. Actelion will continue the VISION trial, initiated by CoTherix, which evaluates
`the safety and efficacy of Ventavis® in combination with orally available therapies. In addition,
`Actelion is exploring ways to improve the inhalation device and formulations of Ventavis®.
`
`“The established
`position of Tracleer® as
`the first-line, corner-
`stone therapy in PAH,
`a significant increase
`in our Marketing and
`Sales force, ongoing
`geographic expansion
`and a multi-pronged
`competitive strategy
`will keep us on track
`for continued strong
`growth and enable us
`to master the chal-
`lenges of new entries
`to the market in 2007.”
`
`Christian Chavy
`President of Business Operations
`
`Actelion Annual Report 2006
`Discovery
`Inside Story
`
`Clinical Development
`Patient Stories
`Business Highlights
`CEO Interview
`Chairman’s Letter
`People
`CFO’s Letter
`Corporate Governance
`Financial Statements
`Shareholder Information
`
`Drug
`Contacts
`
`11
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`

`

`Business Highlights
`
`Zavesca® continues steady sales growth as key clinical trial progresses
`Actelion’s second product on the market, Zavesca® (miglustat), achieved sales of CHF 25.4
`million in 2006, almost doubling from the previous year. Zavesca®, currently indicated for mild
`to moderate type 1 Gaucher patients unwilling or unable to undergo enzyme replacement
`therapy with Genzyme’s Cerezyme® (imiglucerase), combines a novel mode of action with a
`convenient oral form. The key to capturing a greater share of the current USD 900-million
`market is the MAINTENANCE study, which evaluates whether patients with type 1 Gaucher
`disease treated with imiglucerase remain stable after switching to Zavesca®. Recently gen-
`erated clinical data with Zavesca® in another rare liposomal storage disease, Niemann Pick
`Type C, has led to a regulatory filing in the European Union to expand the label in this indica-
`tion.
`
`Prepared to master new competitive challenges in the PAH market
`The position of Tracleer® as the only approved endothelin receptor antagonist for PAH is end-
`ing as new competitors from the same class enter the market in 2007. Building on the estab-
`lished position of Tracleer® as the first-line, cornerstone therapy for PAH backed by years of
`efficacy and safety patient data, Actelion is prepared to meet this challenge. Based on this
`strong data, the company’s multi-pronged strategy includes a broad outreach program to find
`and treat undiagnosed patients through continued educational efforts, and intensive collab-
`oration with prescribing physicians and key opinion leaders in the scientific community to
`expand existing therapeutic options.
`
`Pfizer’s PAH therapy, Revatio®, which contains the same active ingredient (sildenafil) as
`Viagra®, was launched in the US in 2005 and in major EU countries in 2006. Marketing activi-
`ties by the world’s largest pharmaceutical company have increased awareness about pul-
`monary arterial hypertension and expanded the overall market. Revatio®, which has a differ-
`ent mode of action than Tracleer®, is often prescribed as a complementary therapy to
`Tracleer®. To provide the necessary controlled clinical data for such an approach, Actelion
`has initiated several studies evaluating the safety and efficacy of combining these two
`agents.
`
`Making the most of external business opportunities in 2006
`Actelion’s Strategic Plan states that while the main engine of growth remains the discovery
`and development capabilities of Actelion’s own scientists, seizing external opportunities
`offered by acquisitions, alliances and licensing are an integral part of attaining a long-term
`above-industry growth trajectory.
`
`The acquisition of CoTherix for USD 389 million in 2006 illustrates how these principles are
`translated into action. By acquiring the marketing rights in the US for Ventavis®, Actelion not
`only strengthened its franchise in PAH but also gained a product that will significantly boost
`annual sales revenue. The co-development and co-marketing deal with Roche in 2006 on the
`S1P1 agonist demonstrates how strong alliance partners can accelerate value creation for
`shareholders.
`
`Value creation demands a complete understanding of the goals and challenges ahead.
`Accordingly, Actelion’s management undertook a major communication effort in 2006 to align
`the organization behind its ambitious goal to become one of the world’s leading biopharma-
`ceutical companies.
`
`“In 2006, Actelion
`signed two landmark
`business deals. The co-
`development and co-
`marketing agreement
`with Roche on our
`S1P1 agonist under-
`scores the maturity of
`our scientific capabili-
`ties and our Marketing
`and Sales infrastruc-
`ture. The acquisition of
`CoTherix and the
`licensing rights to
`Ventavis® in the US will
`strengthen our leader-
`ship in PAH and boost
`our annual sales.”
`
`Simon Buckingham
`President of Corporate and Business Development
`
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`

`

`Actelion Annual Report 2006
`Discovery
`Inside Story
`
`Clinical Development
`Patient Stories
`Business Highlights
`CEO Interview
`Chairman’s Letter
`People
`CFO’s Letter
`Corporate Governance
`Financial Statements
`Shareholder Information
`
`Drug
`Contacts
`
`13
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`

`

`Patient Stories
`
`A passionate runner’s comeback after Tracleer®
`(bosentan) treatment
`
`Eva O., a 43-year-old medical technician, had always enjoyed running along the wooded
`trails in the countryside near Sankt Poelten, Austria. In the summer of 2003, she began to
`notice shortness of breath and an uncomfortable pressure in her chest during physical
`exercise, accompanied by sensations of nausea and dizziness. She went to her doctor for
`a check-up, and after a series of medical exams, was diagnosed with idiopathic pulmonary
`arterial hypertension (IPAH).
`Her cardiologist prescribed Tracleer® according to the recommended treatment scheme.
`While Eva responded well to therapy, she belonged to a subgroup of patients who suffer
`from the side effect of elevated enzymes in the liver – a condition that can result in lasting
`damage to this vital organ. Two months after it began, treatment had to be discontinued
`until liver function tests returned to an acceptable level. Eva’s hopes for a therapy that
`would allow her to return to a normal life were crushed, and quickly the feelings of nausea
`and chest pressure returned, limiting her capacity for physical exercise.
`Three-and-a-half months later, Eva’s cardiologist reinitiated Tracleer®, first at 62.5 mg twice
`daily, then gradually increasing the dosage to 125 mg twice daily. This time, Eva did not
`develop elevated liver enzymes. Not only did she tolerate Tracleer® well, but her clinical
`symptoms were clearly reduced over the following six months. Eva was overjoyed to be
`able to return to her favorite jogging trails. “It was an incredible feeling to be able to run
`again,” she said. “I felt like I have been given a part of my life back.”
`
`A life in balance with Zavesca® (miglustat)
`
`Marie B. was always small for her age, and she often complained of terrible stomach pain,
`but what alarmed her parents most were the frequent bruises and bloody noses. After fruit-
`less visits to the family doctor, Marie was referred to the City of Hope Medical Center in Los
`Angeles, California, where she was diagnosed with Gaucher disease. Doctors told Marie’s
`parents that their five-year-old daughter had only 5-10 years to live and that her physical
`activities had to be limited to prevent rupturing an enlarged spleen.
`In the following years, little could be done to treat her aside from surgically removing her
`spleen. Marie continued to experience excruciating stomach pains, often putting her in the
`hospital, but she defied the doctors’ prognosis.
`As an adult, Marie participated in an NIH-conducted clinical trial with the enzyme replace-
`ment therapy imiglucerase for Gaucher disease. She received intravenous infusions for
`several hours every two weeks. Despite frequent travel in her job, Marie was able to con-
`tinue these treatments for the next 12 years.
`Over time, Marie began to suffer from the effects of the intravenous infusions. Scar tissue
`developed over the infusion sites and the pain increased. It became increasingly difficult,
`even for her talented nurse, to access a vein.
`Marie happened to see an article about Zavesca® (miglustat) capsules for the management
`of type I Gaucher disease. She consulted her healthcare providers, Cynthia Tifft MD and
`Sandra Yang at Children’s National Medical Center in Washington DC. Due to issues with
`venous access, the team decided that Zavesca® would be the best option for the manage-
`ment of her disease.
`Marie has been on Zavesca® since 2005. Her disease is stable and her treatment is well toler-
`ated. “Thanks to Zavesca®,” Marie reports, “my veins are healthier, my disease is controlled.”
`
`Irene M. Lang, MD, Center of Vascular Medicine,
`General Hospital Vienna, Austria, and Eva O.
`
`Cynthia Tifft, MD, Children’s National Medical Center,
`Washington DC, USA, and Marie B.
`
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`Actelion Annual Report 2006
`Discovery
`Inside Story
`
`Patient Stories
`Business Highlights
`CEO Interview
`Chairman’s Letter
`People
`CFO’s Letter
`Corporate Governance
`Financial Statements
`
`Clinical Development
`Shareholder Information
`
`Drug
`Contacts
`
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`16
`16
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`Clinical Development
`
`Accelerating the next wave of innovation
`
`Actelion’s Clinical Development department advanced an impressive number of clinical tri-
`als in 2006, comprising 8 compounds in a total of 19 Phase I to Phase III studies. Clinical
`Development has two major priorities: enlarging the company’s foundation of approved
`indications for Tracleer® and Zavesca® in areas of unmet medical need while simultane-
`ously conducting trials with novel compounds promoted from Drug Discovery.
`
`Advancing the field of treatment in pulmonary arterial hypertension
`A major pillar of Actelion’s Clinical Development strategy is to maximize the life cycle value
`of Tracleer® (bosentan) by investigating new medical indications and label extensions.
`Tracleer® is the only orally available dual receptor antagonist of endothelin, a potent vaso-
`constrictor that plays a major role in a number of diseases for which there is no adequate
`treatment. Actelion has pioneered the use of Tracleer® in pulmonary arterial hypertension
`(PAH), a life-threatening disease that severely compromises the functions of the heart and
`lungs. TRAX PMS, a post-marketing surveillance study of 5,000 patients in Europe, con-
`firmed the long-term safety of Tracleer® and consolidated its position as the first-line, cor-
`nerstone therapy for PAH. Clinical Development efforts are strengthening Actelion’s lead-
`ership position in the enlarged indication of pulmonary hypert