Phase 3 trials of treatment combo for hepatitis D expected in 2025
Tobevibart-elebsiran program results could support approval applications
On the heels of positive Phase 2 clinical trial data, Vir Biotechnology is planning for the 2025 launch of a Phase 3 program, dubbed ECLIPSE, to test its treatment combination of tobevibart and elebsiran in adults with chronic hepatitis D.
If positive, the results from the program’s two Phase 3 trials are expected to support regulatory applications for approval of the treatment duo, the company stated in a press release announcing the Phase 2 study data.
Findings from the ongoing Phase 2 SOLSTICE study (NCT05461170) show the treatment combo suppressed the hepatitis delta virus — known as HDV, or hepatitis D — and normalized a liver damage marker in hepatitis D patients.
“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.”
Vir presented SOLSTICE data at a session of The Liver Meeting, hosted by the American Association for the Study of Liver Diseases on Nov. 16 in San Diego.
Planned Phase 3 trials follow positive Phase 2 study data
According to Vir, the Phase 3 program’s design was finalized following a meeting with the U.S. Food and Drug Administration (FDA). The U.S. regulatory agency granted the combination treatment fast track designation for chronic hepatitis D earlier this year.
Additionally, a European Medicines Agency committee has issued a positive opinion on granting the combo orphan drug designation for the treatment of chronic hepatitis D. Both regulatory statuses are meant to accelerate a treatment candidate’s clinical development and regulatory review.
The positive opinion “reflects the potential of this combination to address a critical gap in hepatitis delta care,” Mark Eisner, MD, executive vice president and chief medical officer of Vir, said in a separate company press release.
[A positive opinion on a proposed orphan drug designation in Europe] reflects the potential of this combination to address a critical gap in hepatitis delta care.
Viral infections are the most common causes of hepatitis, or inflammation of the liver. Unique from other hepatitis viruses, however, HDV is only able to infect people who have already been infected with the hepatitis B virus, or HBV.
When individuals with a chronic HBV infection acquire hepatitis D, they’re at an increased risk of serious health outcomes, including irreversible liver scarring and damage, known as cirrhosis, liver failure, and liver cancer.
Tobevibart (VIR-3434) is an antibody designed to neutralize HBV and HDV and stop them from infecting liver cells. Elebsiran (VIR-2218), meanwhile, is intended to limit the production of HBV proteins, including one called hepatitis B surface antigen that the hepatitis D virus needs to survive.
Vir expects that, together, the two treatments will lead to strong and sustained suppression of HDV, thereby preventing serious liver problems.
Tobevibart-elebsiran combo shows benefits in Phase 2 study
The SOLSTICE trial involved patients with chronic hepatitis D. A total of 33 were randomly assigned to receive tobevibart alone, at a dose of 300 mg, once every two weeks, while 32 patients were assigned to receive a combination of tobevibart (300 mg) and elebsiran (200 mg) once a month. The combination treatment patients were dubbed the de novo group.
Another 13 patients initially received either tobevibart or elebsiran, but later switched to the monthly treatment combination; this was named the rollover group. All participants are being treated and monitored for up to 192 weeks, or slightly longer than 3.5 years.
The study’s main goal was to evaluate the proportion of patients who achieved both a virologic response and normalization of alanine transaminase, or ALT, a liver damage marker, after about six months. Virologic response is defined as blood HDV levels below the limit of detection or a certain drop from pretreatment levels.
Previous interim data from 59 participants indicated that the trial goal was being met by most of them after up to about a year of treatment.
The newly announced results showed that all patients given the combination therapy — the de novo and rollover groups — achieved a virologic response after six months, with 41% having no detectable HDV. About half of these patients experienced ALT level normalization.
By comparison, 82% of those on tobevibart alone attained a virologic response, with 30% having undetectable HDV, and 76% achieving ALT normalization.
Overall, 47% of patients in the de novo group, 56% of the rollover group, and 70% of those on tobevibart alone met the study’s main goal after six months. Moreover, 19% of those in the de novo group, 21% of the tobevibart group, and 33% in the rollover group achieved no detectable HDV along with normalized ALT.
Benefits of the combined treatment were sustained or further increased for up to about eight months in the de novo group and for slightly longer than one year in the rollover group.
The therapy combo was generally well tolerated, without reports of treatment-related discontinuations or severe adverse events.
Phase 3 trials will enroll hepatitis D patients with, without cirrhosis
The ECLIPSE program — which will boast two Phase 3 trials and a head-to-head Phase 2 study — will further evaluate the treatment combination in chronic hepatitis D patients with or without cirrhosis.
The Phase 3 ECLIPSE 1 study will test the combo against deferred therapy among patients in areas where the antiviral treatment bulevirtide is not available or its use is limited. Bulevirtide is conditionally approved under the brand name Hepcludex for treating chronic hepatitis D in Europe, but does not have FDA clearance.
The Phase 3 ECLIPSE 2 trial will investigate the treatment combination in patients who have not achieved adequate viral suppression with bulevirtide.
The program also will include ECLIPSE 3, a head-to-head Phase 2b trial comparing the tobevibart-elebsiran combo against bulevirtide in patients who have not received previous bulevirtide treatment.
According to Vir, “ECLIPSE 1 and 2 are Phase 3 trials designed to provide the registrational efficacy and safety data needed for submission to global regulatory agencies.”
ECLIPSE 3, meanwhile, is “designed to provide important supportive data, particularly in Europe, to help establish appropriate pricing and reimbursement in key markets,” the company stated in the press release.
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