Vir Biotechnology receives FDA Breakthrough Therapy Designation and EMA PRIME Designation for Tobevibart and Elebsiran in Chronic Hepatitis Delta
The Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to the combination of tobevibart and elebsiran for the treatment of chronic hepatitis delta (CHD) in adults from Vir Biotechnology.
The Breakthrough Therapy designation is supported by data from the randomized, open-label phase 2 SOLSTICE trial (ClinicalTrials.gov Identifier: NCT05461170), which evaluated the efficacy and safety of tobevibart, a monoclonal antibody targeting hepatitis B virus (HBV) and hepatitis delta virus (HDV), in combination with elebsiran, an HBV-targeting small interfering ribonucleic acid, in adults with CHD.
Study participants were randomly assigned to receive tobevibart 300mg monotherapy (n=33) every 2 weeks or de novo tobevibart 300mg in combination with elebsiran 200mg (n=32) every 4 weeks subcutaneously; those that were part of the tobevibart or elebsiran monotherapy cohorts were able to rollover to receive the combination therapy (n=13).
The primary efficacy endpoints were the proportion of participants with undetectable HDV RNA (defined as an at least 2 log10 decrease from baseline or below limit of detection [LOD]) up to week 24, and alanine aminotransferase (ALT) normalization (defined as ALT below upper limit of normal) up to week 24.
Findings showed 100% of participants taking combination tobevibart and elebsiran achieved an undetectable HDV RNA at week 24; this was sustained in all participants (22/22) at week 36 and those in the rollover cohort (5/5) at week 60. Additionally, ALT normalization was seen in 47% (15/32) of participants in the de novo combination cohort and 56% (5/9) in the rollover cohort by week 24; these results were sustained at week 36.
In another viral clearance indicator endpoint, HDV RNA target not detected (TND) (defined as a level below the lower limit of quantification) was achieved in 41% (13/32) of patients in the combination arms at week 24, and increased to 64% (14/22) at week 36. Notably, 80% (4/5) of the rollover cohort achieved no detectable viral RNA.
Additional results with combined endpoints showed in the de novo combination arm, 47% (15/32) saw an undetectable HDV RNA and ALT normalization. HDV RNA TND and ALT normalization was achieved in 19% (6/32) of participants in the de novo combination arm at week 24 and 27% (6/22) at week 36. In the rollover cohort, 33% (3/9) achieved the endpoint at week 24 and 40% (2/5) at week 60.
The safety profile of tobevibart and elebsiran was consistent with previous studies. Treatment-emergent adverse events were all mild or moderate and similar between all treatment groups, with the most common being influenza-like illness.
Vir Biotechnology announced that the phase 3 ECLIPSE registrational program evaluating tobevibart and elebsiran in CHD will begin in the first half of 2025.
Additionally, the CHMP granted eligibility to PRIME during the CHMP meeting of 9-12 December 2024,
FDA Breakthrough Therapy designation aims to expedite the development and regulatory reviews of investigational therapies for serious conditions that demonstrate promising preliminary clinical evidence and potential improvement over existing therapies. EMA PRIME designation is granted to investigational medicines that target conditions with unmet medical needs for which no treatment option exists, or where they can offer a major therapeutic advantage over existing treatments. It fosters early exchange with the EMA to facilitate robust data collection, high-quality marketing authorization applications and expedited evaluations so that medicines can reach patients earlier. These designations follow FDA Fast Track designation and EMA Committee for Orphan Medicinal Products (COMP) positive opinion on orphan drug designation received earlier this year.
About Tobevibart and Elebsiran
Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen. It is designed to inhibit the entry of hepatitis B and hepatitis delta viruses into hepatocytes, and to reduce the level of circulating viral and subviral particles in the blood. Tobevibart, which incorporates Xencor’s Xtend™ and other Fc technologies, has been engineered to have an extended half-life and was identified using Vir Biotechnology’s proprietary monoclonal antibody discovery platform. Tobevibart is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis B and patients with chronic hepatitis delta.
Elebsiran is an investigational hepatitis B virus-targeting small interfering ribonucleic acid (siRNA) designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen. Current data indicates that it has the potential to have direct antiviral activity against hepatitis B virus and hepatitis delta virus. Elebsiran is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis B and patients with chronic hepatitis delta. It is the first asset in Vir Biotechnology’s collaboration with Alnylam Pharmaceuticals, Inc. to enter clinical studies.