In a news release from mid-December 2021, rare liver disease company Albireo Pharma, Inc. (“Albireo”) shared that positive topline data was available from a Phase 1 clinical trial evaluating A3907 for a variety of cholestatic liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Within the study, researchers evaluated both single and multi-doses of A3907. Through this, they sought to understand the safety, pharmacokinetic and pharmacodynamic profiles, and tolerability of orally-administered A3907.
According to Albireo, A3907 is a systemic apical sodium-dependent bile acid transporter (ASBT) inhibitor. The therapy inhibits ASBT within the kidneys and intestines. Ultimately, this helps the body to remove excess bile acids through urine and stool. As bile and bile acids often build up within the liver in cholestatic liver diseases, drugs like A3907 could help reduce symptoms and damage such as scarring and inflammation.
Within the Phase 1 clinical trial, researchers evaluated orally administered A3907 in healthy participants. 54 participants joined the single-dose study, while 22 joined the multi-dose study. Findings include:
- A3907 was both safe and relatively well-tolerated. No participants discontinued treatment due to adverse reactions. While side effects did occur, the most common side effect was diarrhea.
- Within the trial, researchers reached primary and secondary safety and efficacy goals.
- Preclinical data also highlights how A3907 increased bile acid secretion via urine in mice models of PSC. Additionally, the treatment reduced fibrosis (scarring).
Cholestatic Liver Diseases
Primary Biliary Cholangitis (PBC)
The exact cause of primary biliary cholangitis (PBC), a rare and chronic liver disease, is unknown. However, doctors believe that PBC could be an autoimmune condition in which the body mistakenly attacks the liver’s bile ducts. Some toxins or infections may trigger an autoimmune response. As the body attacks the bile ducts, the ducts become damaged, scarred, and inflamed. Thus, bile is unable to efficiently flow from the liver. As bile builds up, it causes progressively worsening scarring (fibrosis) and advanced scarring (cirrhosis), which can cause liver failure. Symptoms associated with PBC include:
- Severe fatigue
- Pruritus (intense itching), often on the bottoms of the feet
- Skin darkening
- Jaundice (yellowing of the skin, eyes, and mucous membranes)
- Small white bumps under the skin (often around the eyes)
- Dry mouth
- Fragile bones
- Internal bleeding in the throat and stomach
- Swelling of the lower extremities
- Joint and muscle pain
- Chronic diarrhea
- Abdominal distention
Primary Sclerosing Cholangitis (PSC)
Much like PBC, the cause of primary sclerosing cholangitis (PSC) is unknown. However, viral or bacterial infections, autoimmune responses, toxin exposure, or even inflammatory bowel disease (IBD) are thought to play a role. 75% of patients with PSC may have some form of IBD. PSC is a chronic liver disease which causes bile duct inflammation, scarring, and blockages. As bile accumulates, it causes further damage. An estimated 70% of those with PSC are male. Symptoms include:
- Abdominal pain, particularly in the upper right sector
- An enlarged liver
- Bile duct infection