According to a relatively recent news release from biopharmaceutical company Dicerna Pharmaceuticals, Inc. (“Dicerna”), interim data is now available from a Phase 1 clinical trial evaluating belcesiran for patients with alpha-1 antitrypsin deficiency-associated liver disease (AATLD). Developed using Dicerna’s proprietary GalXC RNAi platform, belcesiran showed promise in improving the future of patient care.
Belcesiran and AATLD
SERPINA 1 gene mutations cause alpha-1 antitrypsin deficiency (A1AD), an inherited condition causing low levels of alpha-1 antitrypsin protein. Normally, alpha-1 antitrypsin protects the body against an enzyme called neutrophil elastase, which attacks healthy tissues when alpha-1 antitrypsin is deficient. Thus, low levels of alpha-1 antitrypsin cause a host of health issues, including liver damage when abnormal protein accumulates there. Altogether, researchers estimate that 10% of children and 15% of adults with A1AD develop liver disease. Ultimately, this is characterized by liver scarring (fibrosis and cirrhosis), alongside an increased risk of developing hepatocellular carcinoma. However, no current treatment exists.
Enter belcesiran, an investigational treatment that Dicerna is exploring to fill this unmet need. Belcesiran is administered subcutaneously and works to lower alpha-1 antitrypsin levels. It works by using ribonucleic acid interference (RNAi) to silence genes. In this case, belcesiran targets the gene responsible for alpha-1 antitrypsin malfunction and overproduction. To learn more about belcesiran or the GalXC platform, head over to the Dicerna website.
Within the Phase 1 clinical trial, researchers evaluated belcesiran in healthy adult volunteers. Patients received either a placebo or one of four doses ranging from 0.1 mg/kg – 6.0 mg/kg. Ultimately, researchers wanted to understand the drug’s safety, efficacy, tolerability, pharmacodynamic profile, and pharmacokinetic profile. The findings show that:
- Belcesiran was relatively safe and well-tolerated. Most adverse reactions were mild and the moderate reactions were found to not be associated with treatment.
- Following treatment, patients experienced lowered serum AAT (alpha-1 antitrypsin) by up to a mean of 80% (at the highest dose). In one patient, serum levels reduced by 91%.
Ultimately, a singular dose showed promise in reducing serum AAT levels. Researchers are also exploring 12.0 mg/kg belcesiran as a potential treatment option. However, that data will not be available until a later date.