Givosiran for treating acute hepatic porphyria

Acute hepatic porphyria (AHP) is a rare inherited metabolic disorder caused by a deficiency of the enzymes needed to make haem. It is characterised by high levels of porphyrin precursors, including delta‑aminolevulinic acid and porphobilinogen, in the liver and other tissues. High levels of these substances damage nerve cells and can provoke acute attacks of physical pain. Acute attacks are very rare before puberty and usually start between 15 and 35 years. They are more common in women, who may be at increased risk of having an acute attack during or after pregnancy. Acute attacks are often triggered by factors such as drugs, alcohol, hormones, and infection. AHP is life-threatening because it can lead to seizures and paralysis during acute attacks. It can be debilitating in the long term because of chronic pain, fatigue, nausea and vomiting. AHP is progressive, with attack frequency and severity increasing over time. The condition varies from person to person. There are 4 types of AHP: acute intermittent porphyria, hereditary coproporphyria, variegate porphyria and aminolevulinate dehydratase porphyria. Acute intermittent porphyria is the most common form of AHP in the UK and has the highest symptom burden.

The prevalence of symptomatic AHP is estimated to be 1 in 100,000 people in Europe, which equates to about 560 people in England. Most people recover after 1 attack or a few attacks, but attacks can be recurrent in about 10% of people. People with recurrent severe attacks often have chronic symptoms and may not fully recover from an attack. According to the National Acute Porphyria Service, there are 27 people in the UK having treatment for recurrent severe attacks.

Treatment options for AHP aim to prevent attacks or manage symptoms. They include pain management, stopping medication that could have triggered symptoms, gonadotrophin releasing hormone (GnRH) analogues for hormone-induced attacks in women, and oral or intravenous glucose for acute attacks. Haem arginate is indicated for treating acute attacks of AHP. It is also used outside its marketing authorisation to prevent attacks. Liver transplant may be an option for some people with recurrent severe attacks when other treatment options have not worked.