While the likes of Vir Biotechnology and Johnson & Johnson were highlighting their RNAi approaches to treating hepatitis B at the International Liver Congress (ILC) this week, GlaxoSmithKline and Ionis quietly dropped their data using a rival MOA.
The U.K. Big Pharma said its phase 2a test of GSK3228836, which works as an antisense oligonucleotide, showed “marked reductions” in hepatitis B surface antigen (HBsAg), one of the key biomarkers of the disease, as well as its viral DNA when pitted against placebo.
This was after four weeks of treatment in people with chronic hep B on stable nucleoside or nucleotide analogue (NA) therapy, as well as those who had not had the treatment, which is a standard of care for the disease.
Drilling down into the numbers, GSK said the group given its drug with an NA therapy (which was four patients) saw a numerically greater average [SD] reduction of -2.51 [1.57] log10 IU/ml vs. placebo -0.01 [0.04], n=2, p=0.45 was hit, though the p-values were edging toward not being statistically significant.
Three of these patients had reductions ≥3.0 log10 IU/mL by Day 29, while one additional patient discontinued at Day 4 “and was not included in the analysis,” according to the London-based pharma.
In those not treated alongside NA therapy (n=12), average [SD] reduction reached -1.56 [1.38] log10 IU/ml vs. placebo 0.00 [0.11], n=6, p=0.001. Three of these patients had reductions ≥3.0 log10 IU/mL by Day 29.
Across both treatment groups, of the six patients with HBsAg reductions >3.0 log10 IU/ml, four patients had levels falling below the limit of quantification (0.05 IU/ml). Prolonged HBsAg loss was observed in one-NA treated patient (from Day 36 to Day 113) and one NA-naïve patient (from Day 23 to Day 126).
Reductions in the DNA on the virus was >2 log10 IU/mL in five of 12 NA-naïve patients, while in the the NA-naïve group (n=12), average [SD] reduction reached -1.66 [1.48] log10 IU/ml vs. placebo 0.00 [0.47], n=6, p<0.001.
GSK said its drug was now “on track” to start a phase 2b program “by the end of 2020.”
There was a safety scare after one patient suffered a liver enzyme elevation that was classified as a serious adverse event, although this self-resolved. Safety will continue to be a major issue for all developers, although the RNA data are so far pretty clean at the ILC.
While the use of antisense oligonucleotide technology is being used across several therapy areas, including CNS disorders, its use in hep B is fairly novel and not without its troubles. Roche was tapping the same tech with its RG6004 in hep B, moving the drug into the clinic back in 2017 but then dumping the program at the start of this year.
It promptly signed a pact with Dicerna Pharmaceuticals based on its early-stage work on an RNAi approach to the disease.
This appears to be the favored method, with Vir and partner Alnylam as well as Arrowhead and partner J&J also presenting data at ILC 2020 showing they could also hit prolonged HBsAg loss.
RELATED: ILC: Searching for a functional cure while battling rivals, Vir and Alnylam post hep B data peek
“Chronic hepatitis B affects around 260 million people globally and, despite existing treatments, can lead to nearly 900,000 deaths per year due to liver failure and liver cancer,” said Christopher Corsico, senior vice president of development at GSK.
“We have observed promising early-stage results showing antiviral activity with our anti-sense oligonucleotide, a key investigational medicine in our growing infectious diseases portfolio. This marks a potential step forward toward the goal of assessing sustained functional cure for people with chronic hepatitis B.”