Vir Biotechnology Advances Hepatitis D Combo Therapy to Phase 3 Trials
核心洞察
Vir Biotechnology plans to launch Phase 3 trials (ECLIPSE program) in 2025 for its tobevibart and elebsiran combination therapy for chronic hepatitis D (搜索).
Phase 2 SOLSTICE study data showed the combo suppressed hepatitis delta virus and normalized liver damage markers in patients with hepatitis D (搜索).
The FDA granted fast track designation to the combination treatment for chronic hepatitis D (搜索), and the EMA issued a positive opinion on orphan drug designation.
Vir Biotechnology is set to initiate Phase 3 clinical trials in 2025 for its combination therapy of tobevibart and elebsiran, targeting adults with chronic hepatitis D (搜索). This follows promising Phase 2 clinical trial results, signaling a potential breakthrough in treating this challenging liver disease. The Phase 3 program is named ECLIPSE.
The announcement was made following the presentation of positive data from the ongoing Phase 2 SOLSTICE study (NCT05461170). The data demonstrated that the treatment combination effectively suppressed the hepatitis delta virus (HDV (搜索)) and normalized alanine transaminase (ALT) levels, a key marker of liver damage, in hepatitis D (搜索) patients.
SOLSTICE Trial Results
The SOLSTICE trial involved patients with chronic hepatitis D (搜索). Participants were randomized to receive either tobevibart alone (300 mg every two weeks) or a combination of tobevibart (300 mg) and elebsiran (200 mg) once a month. The study's primary endpoint was to assess the proportion of patients achieving both a virologic response (HDV (搜索) levels below the limit of detection or a significant drop from baseline) and normalization of ALT levels after six months.
Results showed that all patients in the de novo and rollover groups achieved a virologic response after six months, with 41% having no detectable HDV (搜索). Approximately half of these patients also experienced ALT level normalization. In comparison, 82% of those on tobevibart alone attained a virologic response, with 30% having undetectable HDV, and 76% achieving ALT normalization.
ECLIPSE Phase 3 Program
The ECLIPSE program will consist of two Phase 3 trials and a head-to-head Phase 2 study to further evaluate the tobevibart-elebsiran combination in chronic hepatitis D (搜索) patients, both with and without cirrhosis (搜索). The program design was finalized after discussions with the FDA, which previously granted fast track designation to the combination therapy for chronic hepatitis D.
The ECLIPSE 1 study will evaluate the combo against deferred therapy in regions where bulevirtide is not available or its use is restricted. ECLIPSE 2 will investigate the treatment combination in patients who have not achieved adequate viral suppression with bulevirtide. The program also includes ECLIPSE 3, a Phase 2b trial comparing the tobevibart-elebsiran combo directly against bulevirtide in patients who are bulevirtide-naive.
Regulatory Landscape and Market Need
Hepatitis D (搜索) is a severe form of viral hepatitis that only affects individuals already infected with the hepatitis B (搜索) virus (HBV). Co-infection with HDV (搜索) and HBV significantly increases the risk of cirrhosis (搜索), liver failure, and liver cancer (搜索). There are limited treatment options available globally, and no approved therapies exist in the United States for hepatitis D.
"People living with hepatitis delta in the U.S. have no approved treatment options, and therapies are limited globally," said Marianne De Backer, PhD, CEO of Vir. "We are confident that our regimen has the potential to deliver transformative benefits for patients, and we will build on our strong SOLSTICE data to start our Phase 3 registrational ECLIPSE program as soon as possible in 2025."
Tobevibart (VIR-3434) is an antibody designed to neutralize both HBV and HDV (搜索), preventing them from infecting liver cells. Elebsiran (VIR-2218) aims to limit the production of HBV proteins, including hepatitis B (搜索) surface antigen, which HDV requires for survival. Vir anticipates that the combined action of these two treatments will result in robust and sustained suppression of HDV, thereby averting serious liver complications.