Investigational Hepatitis D Monoclonal Antibody Achieves 100% Virologic Response

Hepatitis D (HDV) can be a very severe infection, and it is characterized as a satellite virus as it only infects people who have hepatitis B (HBV). According to the Centers for Disease Control and Prevention (CDC), there is a type called coinfection, which happens when people contract both HBV and HDV simultaneously, and it can typically cause short health problems up to even liver failure, but is not typically chronic in nature.¹

However, there is another type of the disease, named superinfection, which happens when someone develops HDV after already having been infected with HBV. This can lead to chronic disease, and includes rapid development of severe conditions such as liver fibrosis and liver failure, and can lead to death.¹

“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,” Kosh Agarwal, MD, consultant hepatologist and transplant physician of the Institute of Liver Studies at King’s College Hospital in London, United Kingdom, said in a statement. Agarwal has been studying a new monoclonal antibody for HDV.²

There are HBV vaccines, but no FDA approved therapies, therefore there is a need for treatment.

Today, Bluejay Therapeutics, a clinical-stage biopharmaceutical company, announced new data from its phase 2 study of BJT-778, an investigational, high-affinity monoclonal antibody (mAb) achieved 100% virologic response across all dose arms and up to 78% of participants reached the combined endpoint of virologic response and ALT normalization. These parallel declines in HDV viral load and ALT were observed across all doses, indicating a beneficial effect on liver inflammation as the result of viral load reduction.²

The results are being presented at The Liver Meeting 2024 of the American Association for the Study of Liver Diseases (AASLD) that is currently ongoing. “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 [chronic hepatitis D],” said Agarwal, who isa presenting author at hte conference.²

The antibody targets hepatitis B virus surface antigen (anti-HBsAg).²

This was a phase 2 study, and participants who were included demonstrated quantifiable HDV RNA and HBV suppressed on nucleos(t)ides were assigned to one of three doses of BJT-778: 300 mg weekly (QW) (n=18); 600 mg every week for 12 weeks, then every two weeks (Q2W) (n=11); and 900 mg every four weeks after a loading dose administered at week two (Q4W) (n=18). Patients with compensated cirrhosis and those with well-controlled HIV were allowed.²

Key endpoints of the study include safety and tolerability; virologic response (defined as ≥2 log10 HDV RNA IU/mL reduction from baseline or HDV RNA target not detected [TND]; ALT normalization in those participants with abnormal ALT at baseline; and the combined response of virologic response plus ALT normalization. According to FDA guidance, this combined endpoint is a reliable predictor of clinical benefit and directly supports approval of new drugs in CHD.²

According to Bluejay, 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; and
• 900 mg Q4W (n=8): By Week 24, had 100% virologic response, including 75% <LLOQ and 50% <LLOQ, TND.²

They also reported a favorable safety profile of BJT-778 with all doses being safe and well tolerated. There were no ≥ grade 3 AEs, no severe AEs and no treatment discontinuations due to AEs.²

The company expects to share longer-term, 48-week data across all dose arms in the second half of 2025.

References

1.Hepatitis D Basics. CDC. April 24, 2024. Accessed November 15, 2024.
https://www.cdc.gov/hepatitis-d/about/index.html#:~:text=About

2.Bluejay Therapeutics Reports Best-in-Class Monoclonal Antibody BJT-778 Achieved 100% Virologic Response and Up To 78% Combined Virologic Response and ALT Normalization as Monotherapy in Participants With Chronic Hepatitis D (CHD). Bluejay Therapeutics press statement. November 15, 2024. Accessed November 15, 2024.
https://www.globenewswire.com/news-release/2024/11/15/2982134/0/en/Bluejay-Therapeutics-Reports-Best-in-Class-Monoclonal-Antibody-BJT-778-Achieved-100-Virologic-Response-and-Up-To-78-Combined-Virologic-Response-and-ALT-Normalization-as-Monotherapy.html