Dicerna guides Roche-partnered hepatitis B drug past early test

Dicerna CEO Douglas Fambrough
Dicerna CEO Douglas Fambrough (Dicerna)

Dicerna Pharmaceuticals has shared interim phase 1 data on its Roche-partnered hepatitis B drug RG6346. The trial linked RG6346 to reductions in hepatitis B surface antigen (HBsAg) that suggest the RNAi therapy can hold its own against rival candidates in development at Johnson & Johnson and Vir Biotechnology.

Roche paid $200 million upfront for a global license to RG6346 in October, giving it a spot in a race that J&J entered in 2018 by handing Arrowhead $250 million. Dicerna landed the Roche deal before publishing clinical data on the therapy, making today’s update the first significant chance to evaluate how the asset stacks up against the competition.

After 122 days, patients who received the 3 or 6 mg/kg dose had experienced a mean reduction in HBsAg of around 1.8 log10 IU/mL. That compares to reductions of 1.6 and 2.0 log10 IU/mL in the Vir and J&J studies, respectively.

Dicerna also has early evidence of the durability of its treatment. The reductions seen at 112 days have been maintained across subsequent analyses, with some assessment-to-assessment variation. Dicerna has the most follow up on a patient in the 1.5 mg/kg cohort, who had a 2.2 log10 IU/mL reduction at day 392.

Some patients experienced transient flares in the liver enzyme alanine aminotransferase after taking RG6346. However, overall liver synthetic and excretory functions were preserved, and no subjects discontinued on safety grounds or experienced dose-limiting toxicities.  

The data come from a small number of subjects—Dicerna enrolled 27 hepatitis B patients across two cohorts—but have offered encouragement to Roche, which wants to develop a finite-duration drug that drives lasting reductions in circulating viral DNA.   

“We are very encouraged by these early results,” John Young, global head of infectious diseases at Roche pRED, said in a statement. “The level and durability of HBsAg reduction seen in this trial is of great interest, and we look forward to further evaluating the potential of RG6346 in an HBV therapeutic cure regimen.” Roche is responsible for taking the drug into phase 2.

The results provide early validation of Dicerna’s approach to hepatitis B. With two conserved areas of the virus to aim at, Dicerna went with a drug that only targets the S region. Dicerna chose to leave the X region alone after its preclinical research showed hitting both conserved areas of the virus led to shallower, shorter responses. 

Dicerna shared the RG6346 data alongside an update on an ongoing open-label extension study that is assessing the safety and efficacy of nedosiran in primary hyperoxaluria patients. Almost 30% of subjects enrolled in the trial had normal urinary oxalate levels at three consecutive visits.