Actelion

Actelion was a Swiss biopharmaceutical company established in December 1997 and headquartered in Allschwil, near Basel. It was founded by cardiovascular researchers Jean-Paul Clozel and Martine Clozel, together with three colleagues, after funding for Martine Clozel's cardiovascular research program was discontinued at F. Hoffmann-La Roche. The founders retained important intellectual-property rights and created a company focused on developing medicines for rare and orphan diseases. The company's defining scientific contribution was its work on the endothelin system, a biological pathway involved in vascular constriction and disease progression. Actelion's researchers were among the early groups to develop endothelin-receptor antagonists, a class that became central to treatment of pulmonary arterial hypertension (PAH). PAH is a rare, progressive disorder in which elevated pressure in the pulmonary arteries places a severe burden on the heart and lungs. Actelion's first major commercial success was bosentan, marketed as Tracleer, which became the first widely used oral endothelin-receptor antagonist and transformed the company's financial and commercial position. Actelion expanded beyond its initial PAH franchise into additional rare, metabolic, oncological, cardiovascular and immune-related conditions. Its portfolio included Zavesca (miglustat) for selected patients with type 1 Gaucher disease, Ventavis (iloprost) for PAH, Veletri (epoprostenol) for severe pulmonary hypertension, and Valchlor (mechlorethamine) for mycosis fungoides-type cutaneous T-cell lymphoma. Later PAH products included Opsumit (macitentan), a next-generation endothelin-receptor antagonist, and Uptravi (selexipag), an oral prostacyclin-receptor agonist developed with Nippon Shinyaku. These products helped Actelion build a broad PAH treatment platform rather than relying on a single medicine. The company financed its early development with venture capital from a syndicate that included Atlas Venture, Sofinnova and HealthCap. It commercialized products through a network of international subsidiaries and affiliates in countries including the United States, Canada, Brazil, Australia, Japan, Switzerland, the United Kingdom, France, Germany and Austria. Actelion also pursued external growth. Its acquisition of California-based CoTherix in 2007 added Ventavis and other cardiopulmonary assets, although the termination of a CoTherix agreement concerning fasudil led to prolonged litigation with Asahi. Actelion combined commercial drug development with support for scientific research. In 2006 it established the Actelion Endothelin Research Award program, intended to support selected clinical research projects concerning endothelin biology and related diseases. The company also investigated technologies and partnerships aimed at improving diagnosis and monitoring of pulmonary hypertension, including work involving imaging and artificial-intelligence methods. In January 2017, Johnson & Johnson announced an agreement to acquire Actelion for approximately $30 billion. The transaction separated Actelion's established commercial medicines from much of its discovery and early-development research. The research organization and selected pipeline assets became Idorsia, a new company founded by the Clozels and listed on the SIX Swiss Exchange in 2017. Actelion's commercial operations became part of Johnson & Johnson's Innovative Medicine business. The brand therefore continued within Johnson & Johnson even though Actelion ceased to exist as an independent listed company. Some acquired development programs were later discontinued, while the established PAH franchise remained strategically important to Johnson & Johnson's cardiovascular and pulmonary-medicine activities.

Actelion emerged from a research and financing break with Roche in the late 1990s. Jean-Paul and Martine Clozel and three colleagues formed the company in December 1997 to pursue medicines for rare diseases and cardiovascular disorders. Early venture financing came from investors including Atlas Venture, Sofinnova and HealthCap. The founders retained rights to intellectual property related to their previous research, including a molecule that became bosentan. The company's early scientific identity was built around endothelin receptors. Endothelin is a potent vasoconstrictor and signaling molecule implicated in pulmonary vascular disease. Actelion's work helped establish endothelin-receptor antagonism as an important therapeutic approach. Bosentan, marketed as Tracleer, became the company's leading medicine and one of the first oral treatments for pulmonary arterial hypertension. Its success enabled Actelion to build a global commercial infrastructure and invest in additional rare-disease programs. During the 2000s and 2010s, Actelion broadened its portfolio and geographic reach. Its products addressed PAH and other cardiopulmonary conditions, Gaucher disease, and selected forms of cutaneous T-cell lymphoma. The company operated affiliates across Europe, Asia, North and South America and Australia. It also established the Actelion Endothelin Research Award in 2006 to support external clinical research. External transactions contributed to the company's expansion. In 2007 Actelion completed its acquisition of CoTherix, a California biopharmaceutical company whose commercial product included Ventavis, an inhaled iloprost treatment for PAH. The acquisition also produced a dispute over the termination of a fasudil development and commercialization arrangement involving Asahi. The matter became a notable example of litigation over contractual obligations following an acquisition. Actelion developed a second generation of PAH products. Opsumit, or macitentan, extended the company's endothelin-receptor-antagonist franchise, while Uptravi, or selexipag, added an oral medicine acting through the prostacyclin pathway. The company also pursued pipeline programs in pediatric PAH, portopulmonary hypertension and Clostridioides difficile-associated diarrhea, although not every program reached commercialization. The company experienced increasing regulatory and legal pressure as the value of its commercial franchise grew. In the United States, authorities alleged that Actelion supported copay assistance for Medicare patients through a charitable foundation in a way that steered demand toward its products and enabled price increases. Actelion agreed to a $360 million civil settlement in 2018; the settlement resolved the government's allegations and did not constitute an admission of criminal wrongdoing. In January 2017 Johnson & Johnson agreed to acquire Actelion for approximately $30 billion. The transaction was designed to combine Actelion's commercial portfolio with Johnson & Johnson's global pharmaceutical platform while placing the research organization and selected early-stage assets into Idorsia. Idorsia was established in 2017 and listed on the SIX Swiss Exchange. Actelion's commercial activities continued under Johnson & Johnson's Innovative Medicine organization, ending Actelion's period as an independent publicly traded Swiss company.

1. 2018Copay-assistance settlement

   Actelion agrees to pay $360 million to resolve United States allegations involving charitable copay assistance and Medicare prescriptions.

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2. 2017Johnson & Johnson announces acquisition

   Johnson & Johnson agrees to acquire Actelion for approximately $30 billion, with research activities separated into a new company.

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3. 2017Idorsia is spun out

   Former Actelion discovery and early-development activities become Idorsia, which lists on the SIX Swiss Exchange.

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4. 2007CoTherix acquisition closes

   Actelion completes its acquisition of CoTherix, adding cardiopulmonary assets including Ventavis.

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5. 2006Endothelin Research Award is established

   Actelion creates a research-award program to support selected clinical projects involving endothelin biology and related diseases.

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6. 2000Actelion becomes publicly listed

   Actelion shares begin trading on the Swiss exchange, supporting the company's expansion as a commercial biopharmaceutical business.

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7. 1997Actelion is founded

   Jean-Paul and Martine Clozel and three colleagues establish Actelion in Switzerland to develop medicines for rare diseases and cardiovascular conditions.

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Specialist biopharmaceutical innovator focused on rare diseases, pulmonary arterial hypertension and other serious cardiopulmonary conditions, with a research heritage centered on endothelin biology.

• Tracleer (bosentan)Pulmonary arterial hypertension

  Tracleer is an oral dual endothelin-receptor antagonist and Actelion's foundational commercial medicine. It was developed for pulmonary arterial hypertension and helped establish oral endothelin-pathway treatment as an important option for patients with this rare, progressive disease. The product became the company's principal revenue generator and supported the development of later PAH therapies.

• Opsumit (macitentan)Pulmonary arterial hypertension2013

  Opsumit is a next-generation oral endothelin-receptor antagonist developed for pulmonary arterial hypertension. It extended Actelion's expertise in the endothelin pathway and became one of the company's major commercial products. The medicine was designed to help delay disease progression and reduce the clinical burden associated with PAH.

• Uptravi (selexipag)Pulmonary arterial hypertension2016

  Uptravi is an oral selective prostacyclin-receptor agonist for pulmonary arterial hypertension. Originally developed by Nippon Shinyaku, it gave Actelion a mechanism complementary to its endothelin-receptor-antagonist products and was used in combination-treatment strategies for eligible patients.

• Ventavis (iloprost)Pulmonary arterial hypertension2004

  Ventavis is an inhaled formulation of iloprost used for pulmonary arterial hypertension. Actelion obtained the product through its acquisition of CoTherix. It represented an established prostacyclin-pathway approach for patients with significant functional limitations and broadened Actelion's cardiopulmonary portfolio.

• Veletri (epoprostenol)Pulmonary arterial hypertension

  Veletri is an injectable epoprostenol product for long-term intravenous treatment of severe pulmonary hypertension. It was aimed at patients with advanced disease who did not respond adequately to conventional therapy and complemented Actelion's oral and inhaled PAH medicines.

• Zavesca (miglustat)Rare metabolic disease

  Zavesca is an oral miglustat treatment associated with rare metabolic disease care, including selected patients with mild to moderate type 1 Gaucher disease for whom enzyme-replacement therapy is unsuitable. It demonstrated Actelion's effort to build a rare-disease portfolio beyond pulmonary vascular medicine.

• Valchlor (mechlorethamine)Oncology2013

  Valchlor is a topical mechlorethamine gel for certain cases of mycosis fungoides, a form of cutaneous T-cell lymphoma. The product gave Actelion exposure to orphan oncology and addressed a rare skin manifestation of non-Hodgkin lymphoma.

• 2006Actelion Endothelin Research Award

  International

  Actelion created an award program supporting selected clinical research projects related to endothelin science and diseases affected by the pathway.

  Outcome. Established a continuing external-research and scientific-engagement platform.

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• 2018Discontinue a phase III development programStrategy

  Johnson & Johnson reviewed development assets inherited through the Actelion transaction.

  What changed. Johnson & Johnson announced that it would discontinue development of one acquired phase III drug program.

  Aftermath. The decision narrowed the inherited development pipeline while the established commercial portfolio continued.

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• 2017Accept Johnson & Johnson acquisitionM&A

  Actelion had developed a substantial commercial rare-disease and PAH franchise, while Johnson & Johnson sought to expand its specialty-medicines platform.

  What changed. Actelion agreed to be acquired by Johnson & Johnson for approximately $30 billion. Research and early-development activities were separated into Idorsia.

  Aftermath. Actelion ceased to be an independent listed company and its commercial operations became part of Johnson & Johnson Innovative Medicine.

  announced transaction value. Approximately $30 billion (2017 announcement)

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• 2007Acquire CoTherixM&A

  CoTherix provided Actelion with cardiopulmonary development and commercial capabilities, including the Ventavis product.

  What changed. Actelion completed the purchase of all CoTherix stock after agreeing to a cash transaction.

  Aftermath. The acquisition expanded Actelion's PAH portfolio but was followed by litigation over the termination of a fasudil-related agreement.

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• 2018Medicare copay-assistance allegationsControversy

  The United States alleged that Actelion used charitable copay-assistance arrangements to support Medicare patients receiving its medicines, including Tracleer, in a manner that could steer prescriptions and facilitate price increases. Actelion paid $360 million to resolve the civil allegations. The settlement was not a criminal conviction.

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• 2018Generic Tracleer litigation is reported

  Drug purchasers brought litigation alleging that Actelion improperly delayed or restricted generic competition to bosentan. The available reference material identifies the litigation but does not establish a final outcome.

  LawsuitRegulation
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• 2017Johnson & Johnson agrees to acquire Actelion

  Johnson & Johnson announced an agreement to acquire Actelion for approximately $30 billion. The transaction included a structure separating Actelion's commercial medicines from its research and early-development activities.

  M&A
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• 2017Idorsia is created from Actelion research operations

  Actelion's discovery research organization and selected early-stage assets were transferred into Idorsia, which subsequently became a separately listed Swiss pharmaceutical company.

  M&A
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• 2013Asahi litigation follows termination of the fasudil program

  A dispute connected with Actelion's acquisition of CoTherix concerned the termination of work under a licensing arrangement for fasudil. The dispute generated arbitration and subsequent court proceedings involving Asahi.

  Lawsuit
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1. Actelion
2. Johnson & Johnson to acquire Actelion
3. Actelion Pharmaceuticals U.S. Inc. agrees to pay $360 million
4. Idorsia: our history