#NACFC2021 – Orkambi and Symdeko may improve children’s liver health

Emerging evidence suggests that treatment with Orkambi (lumacaftor/ivacaftor) and/or Symdeko (tezacaftor/ivacaftor) may reduce liver damage in children and adolescents with cystic fibrosis (CF) who have liver disease.

“We detected improvements in validated non-invasive biomarkers of liver fibrosis [scarring] and cirrhosis in children and adolescents treated with these therapies,” the researchers wrote in a poster presented at the 2021 North American Cystic Fibrosis Conference (NACFC), which will be held virtually November 2-5.

The research results were discussed in a presentation titled “Impact of lumacaftor/ivacaftor and tezacaftor/ivacaftor on pediatric liver health.”

Orkambi and Symdeko are both combination therapies containing two CFTR modulators – drugs designed to increase the functionality of the CFTR protein, the defect of which causes cystic fibrosis, in patients with specific disease-causing mutations.

Cystic fibrosis is generally considered a lung disorder, given the buildup of abnormally sticky, thick mucus it creates. But liver disease can be a serious problem in cystic fibrosis. Indeed, cirrhosis, a form of advanced liver fibrosis (scarring), is the third most common cause of death in people with the genetic condition.

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Although Orkambi and Symdeko have been shown to be effective in improving lung function in eligible patients, their effect on liver health is not well understood.

Now, a team of scientists from Stanford University in California have performed an analysis of data from 50 children and adolescents with cystic fibrosis who were treated with Orkambi and/or Symdeko at their center. All patients were treated for at least six months and their liver health was assessed before and after treatment. These patients had a mean age of 11.2 years at the start of CFTR modulator treatment.

Of the 50 children, 12 had liver damage, defined as evidence of liver damage based on imaging and/or abnormal levels of certain markers of liver health.

Analyzing the data from all the patients collectively, the researchers noted no substantial difference in the occurrence of abnormal liver health tests before and after the start of CFTR modulator treatment. More patients were treated with Orkambi alone than with Symdeko alone, but a total of 18 participants received both therapies.

“Significant changes” were noted in children with liver damage, the researchers said. Specifically, the data indicated that prior to the start of CFTR modulator therapy, platelet levels in these children declined over time. Platelets are cell fragments involved in clotting and are also important indicators of liver and kidney health.

Notably, after patients started treatment, their platelet levels generally stabilized, according to Zachary Sellers, MD, PhD, a Stanford University professor who presented the findings to the NACFC.

The data also suggests that levels of ALT and GGT, two markers of liver damage, decreased after treatment with CFTR modulators in children with liver damage, Sellers said. Such changes were not observed in children without hepatic impairment. Levels of GPR, or GGT-to-Platelet Ratio, a marker of liver scarring, were also reduced with treatment.

“We found that treatment with Orkambi and/or Symdeko improved specific biomarkers of liver injury,” Sellers said.

A separate study, published in August, also found that Orkambi may decrease markers of liver injury in patients with liver impairment, Sellers noted.

Collectively, these data suggest that “CFTR modulators may be beneficial for CF patients with hepatic impairment, even independent of whether the patients have existing lung disease or not,” he concluded.

Editor’s Note: The Cystic Fibrosis News Today team is providing coverage of the 2021 Virtual North American Cystic Fibrosis Conference (NACFC) November 2-5. Go here to see the latest stories from the conference.

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