New immune therapy for chronic hepatitis B slashes virus levels in trial
Developer says VRON-0200 shows potential to improve 'functional cure' rates
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One-time treatment with VRON-0200 reduced hepatitis B virus (HBV) levels in the blood of most people with chronic hepatitis B — early trial findings that suggest the experimental immune-modulating therapy may be effective for patients globally.
That’s according to data from a small clinical study that tested VRON-0200’s safety and early efficacy in patients with chronic hepatitis B infection.
Virion Therapeutics, the therapy’s developer, shared these findings in a poster at the 33rd Conference on Retroviruses and Opportunistic Infections, held Feb. 23-25 in Denver. The poster was titled “VRON-0200 Induced Broad and Sustained Anti-HBV Immunity in Chronically HBV-Infected Patients.”
“VRON-0200 is the first new HBV immune modulator since pegylated interferon to show durable clinical activity with sustained and/or improving anti-HBV responses up to one year (360 days) following a single dose,” Sue Currie, PhD, chief operating officer at Virion and coauthor of the poster, said in a company press release detailing the findings. Pegylated interferon is an approved immune-modulating therapy for hepatitis B.
Currie said the data show that VRON-0200 “has the potential to prevent the need for rescue medications after HBV treatment discontinuation, and [to] improve overall functional cure rates” in chronic hepatitis B. A functional cure means HBV, which causes hepatitis B, is suppressed to a level where antiviral treatments can be discontinued.
HBV is spread by contact with bodily fluids and infects the liver, leading to liver inflammation or hepatitis. In some patients, especially those infected early in life, HBV can result in a chronic infection that can set the stage for life-threatening complications such as liver cancer.
VRON-0200 part of new ‘spark-and-fan’ treatment strategy
VRON-0200, administered via a single injection into the muscle, is an experimental therapy designed to trigger immune cells to more effectively attack HBV. It is being developed as part of a so-called spark-and-fan treatment strategy. The idea is that a one-time treatment with VRON-0200 acts as a spark, initiating an anti-HBV immune response that helps bring down viral levels.
After that, other hepatitis B treatments can be given to fan the flames, further suppressing virus levels to achieve a functional cure.
“VRON-0200 … with its favorable safety and tolerability profile, documented durable clinical activity, and convenient single [into muscle] administration, along with its potential for increased accessibility due to its ease of [scalability] and distribution, make it ideal for global public health initiatives,” said Andrew Luber, CEO of Virion and coauthor of the poster.
Currie added that the spark-and-fan approach “could make VRON-0200 a foundational backbone agent to a wide range of future Functional Cure strategies.”
VRON-0200 … with its favorable safety and tolerability profile, documented durable clinical activity, and convenient single [into muscle] administration, … make it ideal for global public health initiatives [in treating chronic hepatitis B].
The Virson-sponsored Phase 1b clinical trial (NCT06070051), which began enrolling its final patient group last month, is evaluating the safety and preliminary effectiveness of VRON-0200 in adults with chronic hepatitis B.
Early trial testing therapy in people with chronic hepatitis B
The new presentation covers outcomes from 35 participants. The researchers specifically looked at how VRON-0200 treatment affected blood levels of HBsAg, a protein critical for HBV’s ability to infect cells and evade the immune system. It is used as a proxy for viral load.
Eight of the participants received an injection of VRON-0200 followed by treatment with elebsiran and tobevibart, two experimental antiviral therapies being developed by Virion for chronic hepatitis B.
All seven evaluable patients experienced “rapid and profound HBsAg declines” within a week of starting antiviral treatment, the researchers wrote. In three patients, HBsAg levels fell so low that the virus could no longer be detected with standard lab tests.
The scientists noted that these beneficial effects were sustained for the duration of the antiviral treatment — about 5.5 months — and continued for one month after the last dose of antiviral treatment.
“The rapid HBsAg declines seen when combined with investigational antivirals, the ‘fan’ to the VRON-0200 ‘spark’, has the added future potential of shortening combination treatment regimens, and also expansion to other populations,” Currie said, noting that this approach may also help treat other types of viral infection.
The other 27 trial participants were given one or two injections of VRON-0200 without additional experimental antivirals. Reductions in HBsAg levels were detected after about one month and were sustained and/or deepened up to one year in all but four patients. Outcomes were generally similar among patients given one or two injections of VRON-0200.
Across all 35 patients, VRON-0200 was generally well tolerated, with no treatment-related adverse events reported.
Virion is now planning a new Phase 2b clinical trial, dubbed SPARK-B, to further explore VRON-0200 as a potential hepatitis B treatment.
“A Phase 2b SPARK-B trial for HBV Functional Cure is in development and will use the ‘Spark and Fan’ approach to evaluate VRON-0200 in combination with investigational antivirals,” Luber said.
