Summing UP is a new feature where we share the latest porphyria research in easy-to-understand summaries that have been reviewed and approved by the UPA's Scientific Advisory Board of porphyria experts.
Published in Blood May 2023
Original article: https://pubmed.ncbi.nlm.nih.gov/37027823/
This article provides an overview of the current state of research and knowledge about the use of givosiran for treating acute hepatic porphyria.
Acute hepatic porphyrias are a group of 4 genetic disorders related to how the body makes an important molecule called heme in the liver. When one of the steps in the heme-making pathway doesn’t work properly, there is a block in the pathway, and the intermediate products of the heme pathway can build up in the body and cause damage. In acute hepatic porphyrias, it is believed that the buildup of a molecule called ALA can trigger porphyria attacks and chronic symptoms. These attacks cause severe abdominal pain and other neurological impacts.
Givosiran “turns down” the first step of the heme-making pathway using a type of molecule called siRNA. By making the first step of the heme pathway less active, there is a decreased buildup of ALA and other porphyrin precursors leading to decreased symptoms. The givosiran treatment is delivered by monthly injection subcutaneously (just below the skin). This is FDA approved for the treatment of adults with acute hepatic porphyrias. It is typically given in a health care facility but can also be given at home under the supervision of a visiting nurse.
Givosiran was tested in several clinical trials. The clinical trials found that givosiran reduced the rate of porphyria attacks by 74% and improved patients’ quality of life. The trial reported side effects including pain at injection site, nausea, abdominal pain, and, in some patients, impact on kidney and liver function.
Based on the results from the clinical trials, givosiran has been approved in the United States and Europe. Precautions for administering givosiran include monitoring for allergic reactions, and liver and kidney function. Due to lack of data, givosiran is not recommended for people who are pregnant or breastfeeding.
Real world experience with givosiran has found:
The review also identified questions that require further research:
At the end of 2022, there were 520 patients world-wide receiving givosiran. Givosiran is effective at reducing recurrent acute attacks and helps the chronic symptoms of AHP patients. There is still research needed to better understand the long-term effects and safety of givosiran.
CONTENT REVIEWED BY UNITED PORPHYRIAS ASSOCIATION SCIENTIFIC ADVISORY BOARD
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