Actelion Pharmaceuticals, founded in December 1997, emerged as a biotechnology company based in Allschwil, Switzerland. Its core mission centered on discovering, developing, and commercializing innovative drugs, particularly for diseases with unmet medical needs. This focus allowed Actelion to build a reputation for pioneering approaches in challenging medical areas.
Addressing Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension (PAH) is a rare, progressive condition characterized by abnormally high blood pressure in the arteries that carry blood from the heart to the lungs. In PAH, the small blood vessels in the lungs narrow, thicken, or become blocked, making it harder for blood to flow through them. This increased resistance forces the right side of the heart to work harder to pump blood, which can lead to weakening of the heart muscle and eventually right-sided heart failure.
Actelion focused on PAH due to the significant unmet medical need and severity of the condition. Before Actelion’s contributions, patients with PAH faced a grim prognosis, often with a life expectancy of only 7 to 9 years. The disease’s symptoms, such as shortness of breath, fatigue, chest pain, and lightheadedness, are often non-specific, leading to delayed diagnosis, which can worsen the disease’s progression.
Challenges for patients included limited effective treatment options and a progressive decline in quality of life. PAH can be idiopathic, meaning its cause is unknown in many cases, or it can be associated with other conditions like connective tissue diseases, HIV, or congenital heart defects. The disease’s complexity and devastating impact underscored the urgent need for new therapies.
Groundbreaking Drug Therapies
Actelion made significant advancements in PAH treatment with its development of several key drug therapies, each addressing different aspects of the disease. These medications aimed to relax blood vessels, reduce pressure in the lungs, and improve patient outcomes. The company’s research focused on specific molecular pathways involved in PAH progression.
Tracleer (bosentan) was a foundational drug for Actelion, approved by the FDA in 2001 as the first oral medication for PAH. It is a dual endothelin receptor antagonist (ERA) that blocks endothelin-1, a natural substance causing blood vessels to constrict and promoting abnormal growth of vessel walls. By inhibiting endothelin-1 from binding to its ETA and ETB receptors, bosentan helps relax the pulmonary blood vessels, lowering lung pressures and reducing the strain on the right side of the heart.
Opsumit (macitentan) represents a later generation of endothelin receptor antagonists developed by Actelion. Approved in 2013, macitentan also works by preventing endothelin-1 from binding to its receptors, reducing vasoconstriction and proliferation of smooth muscle cells in the pulmonary arteries. Macitentan was specifically designed to have a high affinity and sustained occupancy of these endothelin receptors, contributing to its effectiveness in delaying disease progression and reducing PAH-related hospitalizations.
Uptravi (selexipag), approved in 2015, introduced a different mechanism of action to Actelion’s PAH portfolio. Selexipag and its active metabolite, ACT-333679, are selective agonists of the prostacyclin receptor (IP receptor). Prostacyclin is a natural substance that promotes vasodilation, reduces cell proliferation, and inhibits platelet aggregation. By activating the prostacyclin receptor, selexipag helps widen the pulmonary blood vessels and lowers lung pressures, thereby improving heart function and delaying disease progression.
A New Chapter
In 2017, Actelion Pharmaceuticals was acquired by Johnson & Johnson in an all-cash public tender offer valued at approximately $30 billion. This acquisition allowed Johnson & Johnson to expand its pharmaceutical portfolio in rare diseases by integrating Actelion’s market-leading PAH therapies: Tracleer, Opsumit, and Uptravi. Johnson & Johnson aimed to leverage its global presence and commercial capabilities to enhance patient access.
A distinctive feature of this transaction was the spin-off of Actelion’s drug discovery operations and early-stage clinical development assets into a new, independent Swiss biopharmaceutical company called Idorsia Ltd. Shares of Idorsia were distributed to Actelion’s shareholders as a stock dividend. Jean-Paul Clozel, a co-founder and former CEO of Actelion, became the CEO of Idorsia, leading the new company’s mission.
Idorsia began with a substantial cash position, approximately $1 billion, including a convertible loan from Johnson & Johnson, and a diverse pipeline of clinical-phase drugs. Its focus shifted from Actelion’s established PAH franchise to discovering and developing new and differentiated products across multiple therapeutic areas. Idorsia’s pipeline includes candidates for conditions such as resistant hypertension, systemic lupus erythematosus, and insomnia, aiming to continue a legacy of innovation in areas with unmet medical needs.