Following FDA approval, GigaGen's therapy enters Phase 1 clinical trials as the first recombinant human polyclonal therapy for hepatitis B.
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The new therapy, GIGA-2339, is now set to enter phase 1 clinical trials following a recent FDA approval of the company's investigational new drug (IND) application. Developed by GigaGen, a Grifols company, GIGA-2339 is the first recombinant human polyclonal antibody treatment for HBV and the FDA approved this drug to begin trials in late 2024.2
We followed up with Keller more recently to elaborate on the specific pre-clinical results that demonstrated GIGA-2339's superior potency compared to existing treatments for HBV. Keller stated, “It consists of thousands of antibodies all directed towards the Hepatitis B virus. We call these types of therapies recombinant polyclonal antibody therapies, which are very unique. What we find with our diverse antibody therapy is that it’s over 2000 times more potent than currently available therapies, as demonstrated in both in vitro and in vivo experiments.”
In preclinical studies, GIGA-2339 showed more than 2000 times the potency of current plasma-derived HBV treatments, suggesting it could effectively neutralize and clear the virus. This unique therapy could potentially provide a functional cure for HBV and can be scaled efficiently in a lab setting.2
Regarding the upcoming trials, Keller outlined the objectives and endpoints, “For Phase 1 trials, the primary outcomes typically focus on safety and tolerability, while pharmacokinetics are secondary outcomes. What’s exciting about our upcoming trials is that we have both a single ascending dose and a multi-ascending dose study. The FDA has agreed that the right patient population for this study are those with chronic Hepatitis B infection. We will be exploring various endpoints, including markers of chronic infection, levels of the virus, and surface antigen levels to assess how potent we are in humans at different dose levels,” Keller explains.
Currently, there is no cure for HBV, and existing treatments offer only minimal reductions in HBV protein levels, leaving patients vulnerable to conditions such as hepatocellular carcinoma and cirrhosis. GIGA-2339 aims to address this gap by using more than 1000 anti-HBV antibodies, replicated from the natural immune response of vaccinated donors.2
Keller discussed the scalable nature of GIGA-2339's production in a lab setting, stating, “One of the traditional methods for producing Hepatitis B treatments involves extracting from human plasma, which is a limited resource. To create a potent Hepatitis B drug, you need to continuously vaccinate patients, collect their plasma, and then turn it into a drug. By producing Giga 2339 in the lab at scalable levels, we can meet global demand without relying on patient-derived plasma. If the drug proves to be as potent as expected, we can produce enough to treat the 300 million patients currently suffering from chronic Hepatitis B.”
The development process began with blood from HBV-vaccinated donors, from which GigaGen isolated antibody-producing B cells. These cells were used to extract antibody-coding DNA and create cell lines that produced synthetic human antibodies targeting HBV.1
GIGA-2339 represents the first recombinant human polyclonal antibody therapy for HBV, leveraging a platform designed to replicate the immune responses of top human donors. Keller emphasized the benefit of this approach, saying, “We captured immune systems from people who’ve been vaccinated with the Hepatitis B vaccine, and we took the best immune responses, ran those through our platform, and filtered out the antibodies focused just on Hepatitis B surface antigen…we believe it has a real chance to cure HBV.”1
HBV can be acute (short-term) or chronic (long-term), acute hepatitis B occurs within the first 6 months after exposure to HBV and may cause mild to severe illness. Chronic hepatitis B can develop from acute hepatitis B and may lead to serious liver conditions like cirrhosis and liver cancer.3
The main issue with HBV is that it is highly contagious and spreads through contact with infected blood and body fluids. Many individuals are unaware of their infection, especially in the chronic phase, which contributes to its spread and can lead to severe health issues. Vaccination is the best prevention method, but challenges remain in achieving widespread vaccination and regular screening, particularly in high-risk groups.3
Keller concludes our conversation sharing his excitement for the trials, “Creating thousands of antibodies against a specific disease recombinantly was once considered impossible, and we’re thrilled to show that not only is it possible, but it’s also highly effective in patient populations.”
Watch and listen to our interview from July 2023 with Carter Keller:
