Phase 3 trial of hepatitis D treatment combo enrolls 1st patient
ECLIPSE trial of tobevibart-elebsiran combination starts
The first patient has been enrolled in ECLIPSE 1, a Phase 3 clinical trial testing Vir Biotechnology’s experimental combination of tobevibart and elebsiran in adults with chronic hepatitis D.
This marks the initiation of the Phase 3 ECLIPSE program, data from which, if positive, are expected to support regulatory applications seeking the dual treatment’s approval for hepatitis D, or hepatitis delta.
ECLIPSE 1, which is expected to recruit up to 120 patients in the U.S. and certain regions outside Europe, and a to-be-launched Phase 3 trial called ECLIPSE 2, are expected to serve this purpose.
A Phase 2b trial, ECLIPSE 3, is expected to provide supportive data to help enable access and reimbursement in certain markets, including Europe.
“The start of the ECLIPSE program marks a pivotal moment for patients living with hepatitis delta and for Vir Biotechnology,” Marianne De Backer, PhD, Vir’s CEO, said in a company press release. “This achievement is a testament to our ability to rapidly advance impactful treatments from discovery to patient care.”
Offering hope
Hepatitis, or liver inflammation, is most commonly caused by viral infections. Hepatitis D is caused by the hepatitis delta virus (HDV), which can only infect people who are already infected with the hepatitis B virus (HBV).
People with chronic hepatitis B infection who acquire hepatitis D are at increased risk of irreversible liver scarring (cirrhosis), liver failure, and liver cancer.
Chronic hepatitis D is “the most severe form of chronic viral hepatitis and on average, people living with [chronic hepatitis D] will progress to cirrhosis and liver failure within 5 years,” Vir said.
Approved treatments for hepatitis D are lacking in the U.S. and limited in the EU and other regions. Bulevirtide is cleared for use in Europe, under the brand name Hepcludex, to treat certain chronic hepatitis D patients.
“Chronic hepatitis delta can be a devastating diagnosis, leaving all those impacted in the U.S. facing an uncertain future without approved treatment options,” said Chari A. Cohen, president of the Hepatitis B Foundation. “It is exciting to see potential new therapies for hepatitis delta, such as the combination of tobevibart and elebsiran, which could offer new hope to a community that has been waiting for efficacious treatment options for far too long.”
Tobevibart (VIR-3434) is an antibody-based therapy that works by neutralizing HBV and HDV, stopping them from infecting liver cells. Elebsiran (VIR-2218) is an RNA-based therapy designed to suppress the production of certain HBV proteins, including the hepatitis B surface antigen that HDV needs to infect liver cells.
The combination treatment, given by under-the-skin injections, is expected to suppress HDV infection, thereby preventing serious liver disease and its complications.
Preliminary data from the ongoing Phase 2 SOLSTICE trial (NCT05461170) showed that all chronic hepatitis D patients treated with the tobevibart-elebsiran combo achieved a virologic response after six months. Virologic response is defined as blood HDV levels below the limit of detection or a certain drop from pretreatment levels.
About half the patients showed a normalization of alanine transaminase (ALT), a liver damage marker. These benefits were sustained or deepened for up to more than one year in some cases.
The treatment combination was well tolerated, with no severe adverse events or treatment-related discontinuations.
Safety, efficacy to be assessed
“The data from our SOLSTICE Phase 2 trial suggest that tobevibart and elebsiran can rapidly reduce hepatitis delta virus to undetectable levels, potentially driving important benefit for patients,” said Mark Eisner, MD, chief medical officer at Vir. “We are excited to further evaluate the potential of this combination in our Phase 3 program.”
ECLIPSE 1 will assess the efficacy and safety of tobevibart and elebsiran versus deferred treatment among chronic hepatitis D patients living in the U.S., where bulevirtide is unavailable, and regions where bulevirtide access is limited.
Up to 120 participants will be randomly assigned, in a 2-1 ratio, to receive either the experimental combination or deferred treatment. Patients in the deferred treatment group will receive antivirals against HBV alone for an undisclosed period and then switch to the combination therapy.
The study’s primary goal involves a composite measure of blood HDV levels below the limit of detection and ALT normalization after 48 weeks (nearly one year).
Meanwhile, ECLIPSE 2 will evaluate the efficacy and safety of switching to the experimental combination in chronic hepatitis D patients who have not achieved viral suppression with bulevirtide. ECLIPSE 3 will test the combination therapy in a head-to-head matchup against bulevirtide in patients who have never been treated with bulevirtide.
The tobevibart-elebsiran combo has received breakthrough and fast track designations in the U.S. and priority medicines and orphan drug designations in the EU. These designations are intended to accelerate the development and review of experimental therapies that show potential to address an unmet medical need and offer benefits over existing treatments.
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