Givlaari (givosiran) has demonstrated effectiveness in preventing severe acute attacks and reducing chronic health burden in patients with acute intermittent porphyria (AIP), according to a real-world study conducted in Germany. The study included AIP patients who are commonly excluded from clinical trials, addressing a significant gap in the understanding of Givlaari's efficacy in a broader patient population.
The research, published in the Journal of Clinical Medicine, assessed the therapy's safety and efficacy in AIP patients with both acute and chronic disease manifestations. Researchers at the Porphyria Center at Chemnitz Hospital in Germany treated 28 patients with Givlaari at a starting dose of 2.5 mg/kg for an average of 30 months. The study included patients with sporadic attacks, recurrent attacks, chronic symptoms without attacks, and those receiving regular hemin infusions.
Clinical Improvements and Quality of Life
Overall, 75% of patients experienced clinical improvements with Givlaari treatment. The annualized attack ratio decreased from 2.9 before treatment initiation to 0.45 after six months. This reduction was observed across all patient groups, suggesting that Givlaari can alleviate the recurrence of acute porphyria symptoms in patients with distinct AIP phenotypes.
Patients also showed sustained improvement across all aspects of health-related quality of life, as measured by the EQ-5D-5L questionnaire. Mental health improved by 38%, and pain was reduced by 38%. Patients' ability to perform everyday tasks also improved by 30%. These effects were seen across all patient groups.
Biochemical Response
Before treatment, participants had elevated levels of aminolevulinic acid (ALA) and porphobilinogen (PBG) in the urine, which significantly decreased after three months of treatment. This effect was sustained for up to six months. A biochemical response, defined as a drop to below two times the upper limit of normal, occurred for ALA in all patients and for PBG in about two-thirds after six months of treatment. Three-quarters of the patients saw their ALA levels normalize after six months, while 28% achieved normal PBG levels.
Safety and Tolerability
Six patients reported drug-induced side effects. Two withdrew from the study due to fatigue following three to four months of treatment. Many patients (41%) experienced moderate fatigue after three months of treatment, but for most, it was temporary and eased after six months. Other adverse events included muscle cramps (36%) and nausea (29.1%). Three patients experienced unsatisfactory side effects that led to a dose reduction of 50% to 75%. No life-threatening adverse events were deemed related to treatment.
Implications and Future Research
The researchers noted the importance of these findings given the therapy's high cost, estimated at over USD 400,000 per patient per year. The study highlights Givlaari's potential to transform the lives of patients suffering from AIP with a range of symptoms, including those with chronic symptoms without attacks.
"Our study shows that [Givlaari] treatment has the potential to transform the lives of patients suffering from AIP with a range of symptoms, including those with chronic symptoms without attacks, with a generally satisfactory [adverse event] profile," the researchers wrote.
Further research is required to evaluate whether patients receiving lower or less frequent doses of Givlaari are at a reduced risk of adverse events while continuing to be protected from acute episodes.
