Givlaari safe, effective for acute hepatic porphyria: Real-world data
Treatment led to reductions in disease markers, physical function gains
Givlaari (givosiran) safely led to a complete resolution of annual attacks in people with acute hepatic porphyria (AHP), according to real-world data from a case series study in Italy.
Long-term treatment also led to sustained reductions in key markers of AHP, along with gains in physical function. A trend for reduced pain and fatigue was also seen.
“Our data contribute to the expansion of knowledge on long-term effects and effectiveness of [Givlaari] treatment in real-world practice,” the researchers wrote.
The study, “Effectiveness and tolerability of givosiran for the management of acute hepatic porphyria: A monocenter real-life evaluation,” was published in Molecular Genetics and Metabolism Reports.
AHP is one of four different types of acute porphyria, a disorder marked by disruptions in producing heme, a molecule needed for transporting oxygen in the body. In AHP, these disruptions in heme production lead to the buildup of porphyrins and other heme precursors in the liver.
Results of Givlaari treatment
Givlaari, an RNA-based therapy developed by Alnylam Pharmaceuticals, is designed to block the activity of aminolevulinic acid synthase 1 (ALAS1), an enzyme that’s overactive in AHP, to prevent the accumulation of toxic compounds in cells. Administered via an injection under the skin, Givlaari was approved in the U.S. for adults with AHP in 2019 and in Europe the following year for adults and adolescents.
The approvals were supported by findings from the Phase 3 ENVISION trial (NCT03338816), which showed Givlaari could reduce the annual rate of AHP attacks by 74% compared with a placebo. However, “the long-term effects and effectiveness of the treatment in clinical practice” remained “scant.”
Here, a research team led by scientists in Italy examined the medical records of 11 patients with acute intermittent porphyria (AIP), the most common form of AHP, who were treated with Givlaari, to better understand its real-world safety and effectiveness.
Most patients were women (90%), with a mean age of 37 at the time of disease onset. All received monthly injections of Givlaari (2.5 mg/kg) on top of standard therapy to manage acute attacks. Seven patients received preventive (prophylactic) treatment with heme before starting Givlaari. The patients were followed for a mean of 16 months.
Before treatment, the patients had a mean annual attack rate of seven, which dropped to zero after starting Givlaari.
The therapy also lowered levels of aminolevulinic acid (ALA) and porphobilinogen (PBG), two key AHP biomarkers, in the urine of most or all the patients. ALA reductions were seen in 82% of patients, with levels dropping by a mean of 71.6%. PBG urine levels dropped in all patients by a mean of 75%.
None of the patients showed low blood sodium levels, or hyponatremia, a common complication of AHP, before or during treatment. Blood levels of creatinine, a marker of kidney dysfunction, were normal during treatment, as was the estimated glomerular filtration rate (eGFR), which measures how well the glomeruli, the small filter units in the kidneys, are working to remove waste and excess fluid from the blood. Liver function parameters also remained within a normal range and no one discontinued treatment.
Health-related quality of life data were available for six patients. Significant improvements were seen in perceived physical function after six months of follow-up. A trend towards reduced pain and fatigue was also seen.
“Our real-life experience supports the clinical evidence that long-term treatment with [Givlaari] is well tolerated and able to provide sustained and continuous benefit to patients with AIP,” the researchers wrote.
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