It’s not often a major regulatory body grants conditional approval for a drug based on midstage study data alone. But such is the pressure to deliver a treatment for hepatitis D.
In 2020, the European Medicines Agency conditionally approved Gilead Sciences’ Hepcludex based on a phase 2 study for the treatment of chronic hepatitis D virus infection in adults with compensated liver disease.
“How many other disease indications [would] regulatory authorities give conditional approval after phase 2?” asked Dr. Keting Chu, CEO, founder and chair of Bluejay Therapeutics, a clinical-stage biopharma developing treatments for viral hepatitis and liver diseases. “The regulatory agencies realize how urgent the unmet medical need for this indication is.”
Hepatitis D can lead to a host of devastating symptoms and is the most severe form of viral hepatitis.
“It's much more aggressive than hepatitis B. Basically, 50%-70% of patients will progress into liver cirrhosis, liver failure and liver cancer in five to 10 years,” said Chu.
Despite that urgent need, the treatment landscape for hepatitis D is barren
The FDA rejected Hepcludex’s full approval in 2022 over concerns about the manufacture and delivery of the drug, although Gilead may be gearing up to resubmit to the FDA in 2025. Moreover, Hepcludex is a daily injection with a half-life between four and seven hours and comes with “very significant injection site reactions,” Chu said.
In the meantime, the lack of treatment options in the U.S. remains “very frustrating” for doctors, who must watch their patients “succumb to liver failure,” Chu said.
To help fill that gap, Bluejay Therapeutics is developing BJT-778, a monotherapy for adults with chronic hepatitis D. The company announced positive data from a phase 2 study last month.
A ‘satellite virus’
Known as a “satellite virus” or an “incomplete virus,” hepatitis D can only infect those who’ve also contracted hepatitis B virus, according to the National Organization for Rare Disorders.
It’s estimated that 5%-10% of patients with chronic HBV also have hepatitis D, and the outcome of this co-infection can be severe. Chronic hepatitis D in particular can trigger rapid liver disease progression and death.
With a known incidence of fewer than 200,000 people in the U.S., the FDA considers hepatitis D an orphan disease. But experts believe hepatitis D is underdiagnosed and much more prevalent than estimates show. Not only is it not a reportable disease, there’s not much motivation for doctors to diagnose patients since there’s no treatment, Chu said.
“The regulatory agencies realize how urgent the unmet medical need for this indication is.”
Dr. Keting Chu
CEO, founder, chair, Bluejay Therapeutics
“If you are diagnosed, often they’ll use interferon. It’s the only thing available, and it usually doesn’t work,” she said. “It varies in efficacy, but has fairly severe side effects.”
Treatments on the horizon
Bluejay is one of only a handful of companies developing a hepatitis D treatment. Its candidate, BJT-778 works by targeting the hepatitis B surface antigen HBsAg and binding to it.
“The reason [BJT-778] can be antiviral for [hepatitis D], even though [it] binds to the HBV surface antigen, is that the virus is a very small RNA virus. It does not have a gene encoded in its own envelope. So it has to borrow the HBV envelope to package itself and become a virus, to complete the viral lifecycle,” Chu said.
To overcome this hurdle, BJT-778 has two mechanisms of action, neutralizing the virus and clearing the virus from peripheral blood.
“Because of this, we’re much more potent and we get more rapid antiviral responses,” she said.
The company’s phase 2 data showed that by week 24, BJT-778 achieved 100% virologic response, meaning the virus was undetectable, when the drug was dosed every four weeks. In addition, 78% of patients attained virologic response along with normalizing an enzyme that indicates liver damage when it’s elevated.
BJT-778 also requires fewer injections than Hepcludex and safety data has looked positive, Chu said.“We have no severe side effects and zero discontinuation, which is really different than our competitor,” she said.
In addition, she said BJT-778 takes effect more quickly than Hepcludex — days versus weeks.
Vir Biotechnology also recently announced positive phase 2 results for an investigational human monoclonal antibody and siRNA combination, which is dosed monthly to treat hepatitis D. The biotech is moving into phase 3 testing in 2025.
However, Chu noted that Bluejay’s “monotherapy beats their combination” in terms of efficacy, and Bluejay is working as fast as it can to speed approval.
BJT-778 has already received orphan and PRIME designation from the EMA, and its study endpoint results meet FDA guidance as being a reliable predictor of clinical efficacy. Chu also said the company is applying for a breakthrough designation with the FDA.
“We’re working with both agencies to start our pivotal registrational trial as soon as possible,” she said.
