Sofosbuvir/velpatasvir effective, safe for paediatric HCV

Audrey Abella
25 May 2023
Sofosbuvir/velpatasvir effective, safe for paediatric HCV
Dr Anna Dobrzeniecka presents the findings of the PANDAA-PED study at ESPID 2023.

The direct-acting antiviral (DAA) sofosbuvir/velpatasvir (SOF/VEL) was effective and safe for the treatment of chronic hepatitis C virus (HCV) infection in individuals aged 6–18 years, the PANDAA-PED study has shown.

“In our study, 12-week therapy with SOF/VEL in [this patient cohort] was 100-percent effective, irrespective of age, sex, baseline BMI, HCV genotype, previous ineffective treatment, and extent of liver fibrosis,” said Dr Anna Dobrzeniecka from the Regional Hospital of Infectious Diseases, Warsaw, Poland, at ESPID 2023. “SOF/VEL also has a good safety profile, particularly in younger patients.”

Dobrzeniecka and her team conducted project PANDAA-PED 2019/ABM/01/00014, an open label, nonrandomized clinical trial in 50 patients from all Polish regions. Participants were divided into two weight groups: those who weighed ≥30 kg received SOF/VEL 400/100 mg (n=35), while the 15 participants who weighed between 17 and <30 kg received SOF/VEL 200/50 mg. Treatment duration was 12 weeks. [ESPID 2023, abstract O0061]

Ninety-four percent had vertical infection. Nearly three-quarters had genotype 1 HCV, 20 percent had genotype 3, while 6 percent had genotype 4. Three patients were treatment experienced. Although none had cirrhosis, one 13-year-old patient presented with advanced liver fibrosis (liver stiffness measurement, 11.3 kPa), corresponding to stage F3 in the Metavir scale.

HCV RNA elimination, aminotransferase levels

At visit 1, HCV RNA was detectable in all patients. By visit 2, only two had detectable HCV RNA, 35 had undetectable HCV RNA, while 13 had HCV RNA at the lower limit of detection (<15 IU/mL). By visit 3, almost all had undetectable HCV RNA (n=48). At week 4, all had undetectable HCV RNA.

There were also significant biochemical improvements at week 4, as reflected by the differences in ALT and AST* levels between treatment onset and during and after treatment (p<0.0001 for all timepoints**).

Safety, growth parameters

Thirty-nine patients had adverse events (AEs). Of the 97 AEs reported, two were serious but unrelated to the study drug (yersiniosis and bronchopneumonia with dyspnoea), 33 were possibly drug-related, while 47 were infections and injuries. The most common drug-related AEs were headache (n=9), abdominal pain (n=8), and asthenia (n=6).

“Older children presented with AEs more often. This may encourage starting treatment in young patients,” Dobrzeniecka noted.

At 12 weeks post-treatment, two patients had ALT levels between 1.25 and 1.5 of the upper limits of normal. “[Also,] two patients with initially healthy liver presented with liver steatosis. The patient with advanced liver fibrosis had an improvement in fibrosis from 11.3 to 7.6 kPa (from F3 to F2 in the Metavir scale),” she added.

Mean BMI z-score dropped from start to end of treatment (from 0.44 to 0.34; p=0.01), but the notable differences were between baseline and 12 weeks post-treatment (from 0.44 to 0.27; p=0.001), and between end of treatment and 12 weeks post-treatment (from 0.34 to 0.27; p=0.05). “This requires further investigation and will be analysed at 1 year post-treatment,” noted Dobrzeniecka.

A chance to eradicate HCV

“The WHO recognizes HCV as one of the major public health problems. There are >3 million children living with HCV worldwide,” said Dobrzeniecka. However, most remain undiagnosed, and most national HCV policies lack specific recommendation for HCV testing in children.

‘Is it possible to cure all children with chronic HCV by 2030?’ is a question and time target set by the WHO, noted Dobrzeniecka. “We tried to answer that question [and our findings suggest that despite the high cost,] DAAs may provide the chance to eliminate HCV.”

Further studies are warranted to ascertain the effect of SOF/VEL on children’s growth and the possibility of shortening the treatment duration. The study is also ongoing to assess the long-term treatment effects of SOF/VEL.

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