The European Commission (EC) has approved Alnylam’s Givlaari (givosiran) for adults and adolescents with acute hepatic porphyria (AHP).
Givlaari was previously granted priority medicines designation by the European Medicines Agency, as well as orphan designation in the European Union (EU).
AHP is a group of ultra-rare, genetic conditions, which cause a deficiency of some enzymes needed to produce haem in the liver, leading to an accumulation of porphyrins in the body. AHP has a variety of different symptoms, including severe abdominal pain, vomiting and seizures; attacks of the disease can be life-threatening as they can cause paralysis or respiratory arrest.
Givlaari is an RNA interference therapeutic, created using Alnylam’s platform, which targets aminolevulinic acid synthase 1 (ALAS1). By targeting this enzyme’s mRNA, it reduces the toxins associated with attacks and the other symptoms of AHP.
Alnylam CEO John Maraganore said: “Today’s approval of Givlaari marks a historic moment for patients and families living with this devastating genetic disease, as there are currently no approved medicines in Europe proven to decrease the frequency of attacks and reduce the chronic pain that many patients suffer.”
The EC’s decision to grant marketing authorisation for Givlaari is based on the results of the Phase III Envision study, which assessed the drug in patients with acute intermittent porphyria (AIP), the most common subtype of AHP, over six months.
In the study, Givlaari caused a 74% reduction in the annualised composite rate of porphyria attacks, which are those needing hospitalisation, urgent healthcare visit, or intravenous hemin administration at home, compared to placebo. This was the primary endpoint of the study.
In addition, 50% of patients in the Givlaari group were attack-free at six months, compared to only 16.3% of placebo-treated patients, while the drug group reported significantly lower daily worst pain, compared to the placebo group.
Karolinska University Hospital Porphyria Centre Sweden head Dr Eliane Sardh said: “The fear of not knowing when an attack will strike, combined with ongoing symptoms between attacks, affects every aspect of patients’ lives, limiting their ability to work and maintain a social life.
“In our experience, life is very different for patients since they have been treated with givosiran. In addition to a reduction in the number of porphyria attacks which require hospitalisation and urgent healthcare visits, we have seen improvements in how patients report their overall health status and quality of life, so this approval is truly meaningful for patients, their families and the healthcare professionals who treat them.”
Givlaari’s approval in the EU follows the drug’s approval by the US Food and Drug Administration in November 2019.
Alnylam president Barry Greene commented: “We are committed to bringing Givlaari to patients in Europe as rapidly as possible, and plan to build on our experience in the US by proactively engaging with national authorities in Europe around a value-based agreement framework which we hope will accelerate patient and provider access to Givlaari.”