Our Science

Therapeutic Focus: Prostacyclin

Our focus on Prostacyclin (also called prostaglandin I2 or PGI2) analogues is based on the robust history and research establishing PGI2, a prostaglandin member of the eicosanoid family of lipid molecules, as a potent endogenous vasodilator that possesses antiplatelet, antiproliferative and anti-inflammatory properties. The published data demonstrate that targeting the prostacyclin (IP) receptor can reverse vasoconstriction and enhance cutaneous blood flow, reduce microvascular inflammation, reduce fibrosis, and decrease platelet activation making it potentially relevant for Systemic Sclerosis, a form of Scleroderma.

PIPELINE

SYSTEMIC SCLEROSIS

Iloprost is a stable analogue of PGI2 and a potent prostacyclin (IP) receptor agonist. By mimicking PGI2, it is a vasodilator and inhibitor of platelet activation and fibrosis. Iloprost stimulates generation of cAMP by binding to the IP receptor, thereby affecting phospholipase activity and cytosolic calcium levels in platelets, fibroblasts, and endothelial cells.

The safety and efficacy of intravenous (IV) iloprost in people with Systemic Sclerosis (SSc) who experience frequent, symptomatic digital ischemic episodes (also known as Raynaud’s Phenomenon) is currently being studied in the Phase 3 AURORA Study [Learn More].

*IV Iloprost is not currently FDA approved

Disease Focus: Systemic Sclerosis

Systemic Sclerosis (SSc), a form of Scleroderma, is a rare autoimmune disease characterized by inflammation, immune system dysfunction, vasculopathy, and fibrosis of the skin and internal organs. SSc primarily affects women with an estimated ~75,000 adult cases in the United States. Greater than 95% of people with SSc have evidence of digital ischemic episodes (Raynaud’s Phenomenon) which is the most common presenting feature of SSc.

Digital Ischemic Episodes (Raynaud’s Phenomenon) in Systemic Sclerosis

In 1862, Maurice Raynaud recognized that some people who were exposed to cold temperatures had transient digital ischemia (poor blood flow) as evidenced by demarcated pale or cyanotic skin limited to the digits. The term “Raynaud’s Phenomenon” is used to describe these digital ischemic episodes. 

Symptomatic digital ischemic episodes (Raynaud’s Phenomenon) are characterized by color changes in the fingers (and often the toes) in response to cold exposure or emotion and are associated with symptoms of pain, numbness, discomfort, and/or tingling in patients. 

In people with Systemic Sclerosis (SSc), digital ischemic episodes (Raynaud’s Phenomenon) are often excruciatingly painful and associated with varying symptoms (pain, numbness, tingling, discomfort) and significant disability. This impacts quality of life and day-to-day functioning and may be the initial sign of long-term progressive complications due to inflammation and scarring of the vessels that supply blood to the digits. These slow progressive changes can cause more severe and longer lasting ischemic episodes, that can lead to digital ulcers, or sores, over the fingertips. If untreated, these superficial ulcerations can develop into deep-tissue necrosis with gangrene and ultimately result in amputations. 

There are currently no FDA approved therapies to improve symptoms associated with digital ischemic episodes (Raynaud’s Phenomenon) in patients with SSc. CLICK HERE to learn more about the AURORA phase 3 study.

Digital ischemia in SSc represents a continuum that can progress from Raynaud’s Phenomenon to critical digital loss

SSc results in digital ischemia due to progressive occlusive vasculopathy with compromised vessel lumen

Raynaud’s Phenomenon: experienced by 95% SSc patients1
  • SSc greatly exacerbates normal vasoconstrictive response to cold/stress
  • Symptomatic attacks can be extremely painful and accompanied by numbness, tingling, and loss of dexterity
Digital Ulcers: experienced by >50% SSc patients1
  • Necrotic lesions occurring at distal aspects of digits
  • Can result in amputation, hospitalization, infection, gangrene

Gangrene in 10%, Infection in 26% over 2 years in patients with history of DUs2

Amputation in 16% over 2 years in patients with chronic DUs2

  1. Steen et al. Rheumatology 2009;48:iii19–iii24
  2. Matucci-Cerinic M, Krieg T, Guillevin, et al. Ann Rheum Dis 2016; 75:1770-1776