FDA OKs clinical testing in US of hepatitis D combination treatment

Vir's tobevibart-elebsiran combo also granted fast track status by agency

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by Patricia Inacio, PhD |

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The U.S. Food and Drug Administration (FDA) has approved Vir Biotechnology’s request to conduct clinical testing in the U.S. of a combination of two investigational agents, tobevibart and elebsiran, in people with chronic hepatitis D, also called hepatitis delta.

Right now, tobevibart — used alone or in combination with elebsiran — is being evaluated in an ongoing Phase 2 trial, dubbed SOLSTICE (NCT05461170), that so far has enrolled chronic hepatitis D patients only in Europe and New Zealand. With the investigational new drug (IND) clearance by the FDA, such clinical testing can now be done in the U.S.

Vir also is planning to launch another trial, ECLIPSE, whose data, if positive, are expected to support the filing of an application seeking the combination treatment’s approval for chronic hepatitis D.

Meanwhile, the FDA also simultaneously granted the combo fast track status for the treatment of chronic hepatitis D, a designation meant to expedite the therapy’s clinical development and regulatory review.

These decisions come on the heels of early positive data from SOLSTICE, which showed tobevibart, alone or in combination with elebsiran, reduced levels of the hepatitis D virus and normalized liver damage markers in adults with chronic hepatitis D.

“The IND clearance and fast track designation from the FDA, along with the encouraging preliminary data from our Phase 2 hepatitis delta trial, underscore the potential of tobevibart and elebsiran to transform the treatment landscape for people living with this severe and life-threatening disease,” Marianne De Backer, PhD, CEO of Vir Biotechnology, said in a company press release.

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Viruses are the most common cause of hepatitis, or inflammation of the liver. Among hepatitis viruses, the hepatitis D virus (HDV) is unique as it only infects people who already are infected with the hepatitis B virus, or HBV, which causes hepatitis B.

The co-occurrence of both viruses in the liver enhances the risk of patients for worse outcomes, including irreversible liver scarring, or cirrhosis, liver failure, and liver cancer.

Tobevibart (VIR-3434) is an antibody designed to block the ability of HBV and HDV to enter hepatocytes, the main cells of the liver. Originally developed by Alnylam Pharmaceuticals, elebsiran (VIR-2218) is an RNA-based therapy designed to limit the production of HBV proteins, including the hepatitis B surface antigen, which is key for HDV multiplication.

Both investigational medications are given through under-the-skin, or subcutaneous, injections, and their combination is expected to effectively suppress HDV infection and prevent liver complications associated with chronic infection.

We are committed to working closely with health authorities to bring this potential groundbreaking treatment to patients as quickly as possible, addressing a critical unmet medical need.

The Phase 2 SOLSTICE trial is assessing the two-year safety and effectiveness of tobevibart, alone or in combination with elebsiran, in up to 124 adults with chronic hepatitis D.

A first group of six patients received treatment with either tobevibart or elebsiran alone for three months before starting the combo therapy; this cohort was dubbed the rollover group. Meanwhile, another 32 patients received the combination therapy immediately, and were thus called the de novo group. In both groups, the therapies were given once monthly.

A third group of 33 patients received tobevibart alone, once every two weeks, for up to about one year.

In the rollover group, preliminary data up to nearly one year of follow-up showed that all six patients continued to have a virologic response, and 50% of them had normal levels of the alanine transaminase, a liver damage marker, meeting the trial’s main efficacy goal.

A virologic response is defined by blood levels of HDV below the limit of detection or a certain drop since the study’s start.

All 27 patients in the de novo group achieved a virologic response after three months, and 44% met the main efficacy goal.

SOLSTICE’s six-month data from all participants are expected by year’s end.

In the new ECLIPSE trial, chronic hepatitis D patients will be randomly assigned to receive either the combination therapy, given once a month, or standard treatment.

“We are committed to working closely with health authorities to bring this potential groundbreaking treatment to patients as quickly as possible, addressing a critical unmet medical need,” De Backer said.