Bulevirtide monotherapy sustains virologic, biochemical responses in CHD

Treatment with bulevirtide, either 2 or 10 mg, has shown sustained improvement in virologic and biochemical responses in patients with chronic hepatitis delta (CHD), according to the MYR301 study presented at EASL 2024.

“Combined response, ALT normalization, and virologic response rates increased through week 98 and were maintained from weeks 96–144,” said lead author Dr Pietro Lampertico from the Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy.

The ongoing phase III MYR301 study involved 150 patients with CHD, with or without compensated cirrhosis, who were randomly assigned in a 1:1:1 ratio to receive bulevirtide 10 mg/day from weeks 48–96 (delayed treatment; n=51) or bulevirtide 2 mg/day (n=49) or 10 mg/day (n=50), each administered for 144 weeks.

At week 144, both the 2- and 10-mg bulevirtide groups showed similar rates of combined response (virologic response* and ALT normalization) at 57 percent and 54 percent, respectively. [EASL 2024, abstract LBP-029]

When assessed individually, the virologic response rates were also similar between the bulevirtide treatment arms (74 percent [2 mg] and 76 percent [10 mg]).

With regard to biochemical response, the percentage of patients who achieved ALT normalization at week 144 was comparable between those treated with bulevirtide 2 mg (59 percent) and 10 mg (60 percent).

Additionally, the undetectable HDV RNA rates continued to increase at week 144 for both doses of bulevirtide, although with a numerically higher rate in the 10-mg arm compared with the 2-mg arm (50 percent vs 29 percent).

Of note, baseline predictors of undetectable HDV RNA at week 144 were lower HDV RNA log₁₀ IU/mL (odds ratios [ORs], 2.9; p=0.0145 [2 mg] and 2.1; p=0.0258 [10 mg]) and lower hepatitis B surface antigen (HBsAg) log₁₀ IU/mL (ORs, 5.1; p=0.0319 [2 mg] and 6.0; p=0.0390 [10 mg]).

Throughout the 144-week treatment period with bulevirtide, there was no progression to liver-related outcomes among the patients. Platelet counts, liver chemistries and stiffness, and HBsAg values remained stable or improved, including those with cirrhosis, noted Lampertico.

There were also no serious adverse events, deaths, or drug discontinuations observed in either dose of bulevirtide.

The safety profile was similar between the bulevirtide 2 and 10 mg arms, except for more frequent injection-site reactions in the 10 mg arm, likely due to two daily bulevirtide injections vs one daily injection with bulevirtide 2 mg, Lampertico noted.

“Long-term treatment with bulevirtide monotherapy over 144 weeks remained safe and effective,” Lampertico said. “Improvements in virologic and biochemical responses and liver stiffness, as well as low occurrence of liver-related outcomes, are supportive of the potential clinical benefits of long-term bulevirtide monotherapy.”