Bluejay Therapeutics announced positive results from its Phase 2 study of BJT-778, a fully human monoclonal antibody targeting hepatitis B virus surface antigen (HBsAg), for the treatment of chronic hepatitis D (CHD). The study demonstrated a 100% virologic response across all dose arms, with up to 78% of participants achieving a combined virologic response and ALT normalization.
The data, to be presented at The Liver Meeting® 2024 of the American Association for the Study of Liver Diseases (AASLD), highlight BJT-778's potential as a monotherapy for adults with CHD, the most aggressive form of viral hepatitis. The study included patients with quantifiable hepatitis D virus (HDV) RNA and hepatitis B virus (HBV) suppressed on nucleos(t)ides, who were assigned to one of three BJT-778 doses: 300 mg weekly (QW), 600 mg every week for 12 weeks then every two weeks (Q2W), and 900 mg every four weeks (Q4W) after a loading dose.
Key Findings from the Phase 2 Study
The primary endpoints of the study included safety, tolerability, virologic response (≥2 log10 HDV RNA IU/mL reduction from baseline or HDV RNA target not detected), ALT normalization, and the combined response of virologic response plus ALT normalization. The FDA considers this combined endpoint a reliable predictor of clinical benefit for CHD drug approvals.
"For the more than 12 million patients globally with chronic hepatitis D, the most severe and aggressive form of viral hepatitis, there are limited treatment options," said Kosh Agarwal, MD, Consultant Hepatologist and Transplant Physician of the Institute of Liver Studies at King’s College Hospital in London, United Kingdom. "We need to do better for patients. These BJT-778 phase 2 data show that this monotherapy regimen has the potential to be an important treatment advance in CHD."
By the last timepoint available for each dose, the results were as follows:
- 300 mg QW (n=10): By Week 44, this group had 100% virologic response, including 60% with HDV RNA below the Lower Limit of Quantification (<LLOQ [HDV RNA 10 IU/mL]) and 50% with undetectable HDV RNA (<LLOQ, TND).
- 600 mg Q2W (n=10): By Week 36, had 100% virologic response, including 50% <LLOQ and 40% <LLOQ, TND.
- 900 mg Q4W (n=8): By Week 24, had 100% virologic response, including 75% <LLOQ and 50% <LLOQ, TND.
Safety and Tolerability
BJT-778 demonstrated a favorable safety profile across all doses, with no ≥ grade 3 adverse events (AEs), no severe AEs, and no treatment discontinuations due to AEs.
Future Directions
"BJT-778 has the potential to be both practice-changing for physicians and life-changing for patients," said Nancy Shulman, MD, Chief Medical Officer of Bluejay Therapeutics. "A monotherapy for HDV with 100% virologic response, high rates of ALT normalization, a strong safety profile and convenient dosing regimens is now achievable. These results support advancing BJT-778 into larger, randomized controlled studies and we plan to commence these studies as soon as possible."
Longer-term, 48-week data across all dose arms are expected to be shared in the second half of 2025.
Chronic Hepatitis B Program
Bluejay Therapeutics also presented preclinical data on its chronic hepatitis B (CHB) functional cure development program. The data showed that BJT-778 significantly increased the uptake of hepatitis B surface antigen (HBsAg), leading to enhanced HBV-specific CD4 T cell activation. Additionally, preclinical characterization data on cavrotolimod (CAVRO), a spherical TLR9 agonist, demonstrated selective TLR9 activation and induction of key cytokines, indicating a strong cellular immune response. A Phase 1b study has been initiated to evaluate CAVRO in participants with CHB.
