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Although the study also identified some safety issues with givosiran, an RNA-inhibitor molecule delivered by subcutaneous injection once a month, the increases in liver enzyme levels it produced in some patients as well as decreased renal function did not seem severe or frequent enough to counterbalance the benefits to treated patients, who often have significant comorbidities and adverse effects because of their disease, Manisha Balwani, MD, said at the meeting sponsored by the European Association for the Study of the Liver. Among the 48 patients assigned to the givosiran group, one patient dropped out because of an adverse effect of treatment.
The results put givosiran on track to become the first Food and Drug Administration–approved treatment for acute hepatic porphyria, a set of similar, rare genetic diseases that produce symptoms in about 1 in every 10,000 people, although asymptomatic disease is likely more common (Hepatol Commun. 2019 Feb;3[2]:193-206). The trial outcomes were also notable for the dramatic improvements in life-disrupting symptoms like pain, nausea, and fatigue that many treated patients experienced.
Patients’ lives were “completely transformed” by givosiran treatment, Dr. Balwani said in a video interview. Patients also had a reduced need for analgesics, including opioids, said Dr. Balwani, a medical geneticist at the Icahn School of Medicine at Mount Sinai in New York.
The ENVISION (A Study to Evaluate the Efficacy and Safety of Givosiran [ALN-AS1] in Patients With Acute Hepatic Porphyrias) study randomized 94 patients who were at least 12 years old and diagnosed with an acute hepatic porphyria, and had experienced at least two porphyria attacks during the prior 6 months. The study ran at 36 sites in 18 countries. Enrolled patients averaged about 39 years old, and had been diagnosed with a hepatic porphyria for an average of about 6 years. During the study, patients did not receive hemin (Panhematin) prophylaxis.