RARE Daily

Alnylam Wins European Approval of Givlaari for AHP

March 3, 2020

Rare Daily Staff

The European Commission granted marketing approval to Alnylam Pharmaceuticals’ Givlaari as a treatment of acute hepatic porphyria, a family of ultra-rare, genetic diseases characterized by debilitating, potentially life-threatening attacks.

Acute hepatic porphyria disproportionately impacts women of working and childbearing age, and symptoms of the disease vary widely. Severe, unexplained abdominal pain is the most common symptom, which can be accompanied by limb, back, or chest pain, nausea, vomiting, confusion, anxiety, weak limbs, constipation, diarrhea, or dark or reddish urine. They can also experience seizures, which can be life-threatening due to the possibility of paralysis and respiratory arrest during attacks.

Givlaari is an RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of adults with AHP. In the pivotal study, Givlaari was shown to significantly reduce the rate of porphyria attacks that required hospitalizations, urgent healthcare visits or IV hemin administration at home compared to placebo.

Givlaari is the first approved medicine for AHP in Europe.

The European Commission approval is for use of Givlaari in adults and adolescents aged 12 years and older.

The marketing authorization was based on positive data from the ENVISION phase 3 trial, a randomized, double-blind, placebo-controlled, global, multicenter study to evaluate the efficacy and safety of Givlaari in patients with a documented diagnosis of AHP. The primary endpoint of the study was reduction relative to placebo in the annualized rate of composite porphyria attacks, defined as those requiring hospitalization, urgent healthcare visit, or intravenous hemin administration at home, in patients with acute intermittent porphyria, the most common subtype of AHP, over six months.

“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,” said Eliane Sardh, head of the Porphyria Centre Sweden, Karolinska University Hospital, Sweden. “In our experience, life is very different for patients since they have been treated with [Givlaari]. In addition to a reduction in the number of porphyria attacks which require hospitalization and urgent healthcare visits, we have seen improvements in how patients report their overall health status and quality of life. Some of our patients have been able to achieve significant personal and professional milestones that would not have been possible before.”

Givlaari was granted Priority Medicines (PRIME) Designation by the European Medicines Agency, as well as Orphan Designation in the European Union. Givlaari was also granted an accelerated assessment, which is awarded to medicines deemed to be of major public health interest and therapeutic innovation, and the award is designed to bring new treatments to patients more quickly. This EC approval follows the November 2019 U.S. Food and Drug Administration approval.

Photo: Eliane Sardh, head of the Porphyria Centre Sweden, Karolinska University Hospital, Sweden.

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