Bulevirtide Acetate

SAN FRANCISCO--( BUSINESS WIRE )--Vir Biotechnology, Inc. (NASDAQ:VIR) today announced positive results from the SOLSTICE Phase 2 clinical trial evaluating tobevibart alone, or in combination with elebsiran, in people with chronic hepatitis delta (CHD). The most-advanced and potential first-of-its-kind investigational human monoclonal antibody and siRNA combination dosed monthly achieved 100% virologic response and rapid hepatitis delta virus (HDV) RNA suppression. HDV RNA below the lower limit of quantification (< LLOQ), target not detected (TND), the best measure that the virus is cleared from the body, was achieved in 41% (13/32) of participants at Week 24 rising to 64% (14/22) of participants by Week 36. In a cohort that reached Week 60, 80% (4/5) achieved HDV RNA TND. These data were presented in an oral session at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting ® , in San Diego, CA. Based on these results, and following a recent meeting with the FDA, Vir Biotechnology plans to initiate the Phase 3 registrational ECLIPSE program in the first half of 2025 to further evaluate the combination of tobevibart and elebsiran for the treatment of CHD. CHD is a chronic inflammatory liver disease caused by HDV 1 . It is the most severe form of chronic viral hepatitis 2 and on average, people living with CHD will progress to cirrhosis and liver failure within 5 years 3 . There is no approved treatment in the United States. The objective of therapy is to clear the virus, and combination therapy offers the potential to do so by tackling the viral lifecycle through multiple mechanisms. “ Achieving HDV RNA suppression with a safe, well-tolerated, and conveniently dosed treatment could be transformative for people living with hepatitis delta. The impressive rates of virologic suppression seen in the SOLSTICE Phase 2 data suggest that tobevibart and elebsiran have the potential to significantly improve patient outcomes,” said Tarik Asselah, M.D., Ph.D., Professor of Hepatology at the Hôpital Beaujon, APHP, Clichy, France, and at the University of Paris-Cité, and Head of the unit Viral Hepatitis UMR1149 at INSERM, France. “ New, effective therapeutic options are urgently needed, and I am excited to see this combination advance into a registrational Phase 3 program.” Primary Endpoint Analysis from the Phase 2 SOLSTICE Trial Clinical trial participants were randomized to receive tobevibart 300 mg monotherapy every two weeks (n=33) or a combination of tobevibart 300 mg and elebsiran 200 mg every four weeks (combination de novo arm, n=32). In addition, the participants from previous tobevibart or elebsiran monotherapy cohorts could rollover to receive the combination of tobevibart 300 mg and elebsiran 200 mg every four weeks (combination rollover, n=13). Rates of virologic suppression were evaluated at Week 24, and further assessed at Weeks 36, 48 and 60 in those participants that had reached each timepoint. Further monitoring will continue up to 192 weeks. Rapid and Sustained Virologic Suppression – 100% of participants across combination arms achieved an HDV RNA ≥2 log 10 decrease or below limit of detection (LOD) at Week 24, and this rate was sustained over time in all participants at Weeks 36 (22/22) and those in the rollover cohort that reached Week 60 (5/5). HDV RNA TND was achieved in 41% (13/32) of participants across combination arms at Week 24 and this rose to 64% (14/22) at Week 36. By week 60, this had risen further with 80% (4/5) of participants in the rollover cohort having achieved no detectable viral RNA. Approximately 90% of participants receiving the combination achieved reductions in hepatitis B surface antigen (HBsAg) values below <10 IU/mL at Week 24, with sustained responses at later time points. This indicates suppression of the key biologic mechanisms that HDV requires for viral replication. ALT Normalization – Alanine aminotransferase (ALT) decreased in most participants between Day 1 and Week 24 and normalized in 47% (15/32) of participants in the combination de novo cohort and 56% (5/9) in the rollover cohort by Week 24. These rates were sustained at Week 36. Combined Endpoints – The protocol defined combined endpoint of HDV RNA decrease ≥ 2 log 10 compared to baseline or HDV RNA below LOD and ALT normalization at Week 24 was observed in 47% (15/32) of participants in the combination de novo arm. The more stringent composite endpoint of HDV RNA TND and ALT normalization was achieved in 19% (6/32) of participants in the combination de novo arm at Week 24, which increased to 27% (6/22) by Week 36. This trend was reflected in the combination rollover cohort in which 33% (3/9) of participants achieved this endpoint at Week 24 and 40% (2/5) at Week 60. Rates of HDV RNA suppression and ALT normalization were similar between non-cirrhotic and cirrhotic participants across combination arms. Safety Profile – The safety profile of tobevibart and elebsiran is consistent with previous studies. Treatment-emergent adverse events (TEAEs) were generally mild or moderate and transient across all treatment groups, with influenza-like illness being the most common event. No ALT flares were observed. There were no study-related discontinuations in the combination arms, and no treatment-related severe adverse events (SAEs) were reported. “ People living with hepatitis delta in the US have no approved treatment options, and therapies are limited globally. At Vir Biotechnology we are committed to changing that,” said Marianne De Backer, M.Sc., Ph.D., MBA, Chief Executive Officer, Vir Biotechnology. “ 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.” Phase 3 Registrational ECLIPSE Program Following a meeting with the FDA, Vir Biotechnology finalized the design of the Phase 3 registrational clinical program, ECLIPSE, which evaluates the tobevibart and elebsiran combination in people living with CHD. This program, which will commence in the first half of 2025, will include three randomized, controlled trials designed to evaluate the combination therapy in comparison to deferred treatment or bulevirtide. All studies will enroll both cirrhotic and non-cirrhotic participants. 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 is a Phase 2b trial designed to provide important supportive data, particularly in Europe, to help establish appropriate pricing and reimbursement in key markets. ECLIPSE 1 will assess the efficacy and safety of tobevibart and elebsiran compared to deferred treatment in regions such as the U.S. where bulevirtide is not available or its use is limited. ECLIPSE 2 will evaluate the efficacy and safety of switching to tobevibart and elebsiran in people with CHD who have not achieved viral suppression with bulevirtide therapy. ECLIPSE 3 is a Phase 2b head-to-head trial to evaluate tobevibart and elebsiran compared with bulevirtide in bulevirtide-naïve patients. In June 2024, the U.S. Food and Drug Administration (FDA) granted fast track designation for the combination of tobevibart and elebsiran for the treatment of CHD. This designation is intended to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Vir Biotechnology announced today that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) issued a positive opinion on the application for orphan drug designation of tobevibart and elebsiran for the treatment of CHD. This designation supports the development of treatments for life-threatening or chronically debilitating conditions with significant unmet medical need. Investor Conference Call Vir Biotechnology will host an investor conference call on November 19, 2024 at 5.15 a.m. PT / 8.15 a.m. ET. A live webcast will be available on https://investors.vir.bio/ and will be archived on www.vir.bio for 30 days. About the Phase 2 SOLSTICE Trial SOLSTICE is a Phase 2 study to evaluate the safety, tolerability, and efficacy of tobevibart, alone or in combination with elebsiran, in people with chronic hepatitis delta. This Phase 2 study is a multi-center, open-label, randomized study. Primary endpoints include proportion of participants with undetectable hepatitis delta virus (HDV) RNA (defined as HDV RNA equal or greater than 2 log 10 decrease from baseline or below limit of detection) up to week 24, alanine aminotransferase (ALT) normalization (defined as ALT below upper limit of normal) up to week 24, and treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) up to 118 weeks. Secondary endpoints include proportion of participants with undetectable HDV RNA and different timepoints and up to 192 weeks. More information about this trial can be found at clinicaltrials.gov (NCT05461170). 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. Tobevibart and elebsiran are also being evaluated as a potential functional cure for chronic hepatitis B. Vir Biotechnology recently presented positive safety and efficacy end-of-treatment results from the MARCH Phase 2 clinical study evaluating combinations of tobevibart and elebsiran, alone or in combination with pegylated interferon alfa (PEG-IFNα), in participants with chronic hepatitis B in a late-breaker oral presentation at AASLD The Liver Meeting ® . About Vir Biotechnology, Inc. Vir Biotechnology, Inc. is a clinical-stage biopharmaceutical company focused on powering the immune system to transform lives by discovering and developing medicines for serious infectious diseases and cancer. It’s clinical-stage portfolio includes infectious disease programs for chronic hepatitis delta and chronic hepatitis B infections and programs across several clinically validated targets in solid tumor indications. Vir Biotechnology also has a preclinical portfolio of programs across a range of other infectious diseases and oncologic malignancies. Vir Biotechnology routinely posts information that may be important to investors on its website. References: 1 NIH National Institute of Diabetes and Digestive and Kidney Diseases Hepatitis D - NIDDK (nih.gov) , accessed September 2024 2 WHO Hepatitis Delta Factsheet – Hepatitis D (who.int) , accessed September 2024 3 CDC What is Hepatitis D - FAQ | CDC Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “plan,” “potential,” “aim,” “expect,” “anticipate,” “promising” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Vir Biotechnology’s expectations and assumptions as of the date of this press release. Forward-looking statements contained in this press release include, but are not limited to, statements regarding Vir Biotechnology’s strategy and plans, the potential clinical effects of tobevibart and elebsiran, the potential benefits, safety and efficacy of tobevibart and elebsiran, the timing, nature and significance of data from Vir Biotechnology’s multiple ongoing trials evaluating tobevibart and elebsiran, Vir Biotechnology’s plans and expectations for its CHD and CHB programs, and risks and uncertainties associated with drug development and commercialization. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data or results observed during clinical trials or in data readouts; the occurrence of adverse safety events; risks of unexpected costs, delays or other unexpected hurdles; difficulties in collaborating with other companies; successful development and/or commercialization of alternative product candidates by Vir Biotechnology’s competitors; changes in expected or existing competition; delays in or disruptions to Vir Biotechnology’s business or clinical trials due to geopolitical changes or other external factors; and unexpected litigation or other disputes. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Vir Biotechnology’s filings with the U.S. Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. Except as required by law, Vir Biotechnology assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

New readouts of hepatitis D treatments are prompting optimism that the long-barren set of options for patients might have new options on the horizon. New data from midstage trials from Vir Biotechnology and Bluejay Therapeutics showed that their experimental drugs significantly knocked down levels of virus in patients. Both companies are now gearing up for more trials to advance the drugs. There are currently no FDA-approved treatments for hepatitis D. Gilead, which has shown promising data for its drug bulevirtide, was rejected by the FDA in 2022 over manufacturing and delivery issues. On Friday, Bluejay said that in 28 patients treated across three doses of its drug, all patients had virus that was knocked down by at least 99% or wasn’t detectable after treatment. The test also showed significant improvements in liver function. Bluejay CMO Nancy Shulman said the treatment “has the potential to be both practice-changing for physicians and life-changing for patients.” She added in a subsequent statement to Endpoint News on Monday that Bluejay is talking with regulators about next steps. “The company plans to start larger, randomized, controlled trials as soon as possible,” she said. Vir, in a separate study of its combination therapy, brought down viral RNA loads below quantifiable levels in 41% of treated patients at 24 weeks, and 64% of patients at 36 weeks. Like Bluejay, all patients had knockdowns of at least 99%, and many patients also showed liver function improvements. CEO Marianne De Backer called the batch of results released Monday a “remarkable virological response” in an interview with Endpoints. The company has already finalized its Phase 3 trial design with the FDA and plans to launch that trial in the first half of 2025. Alnylam has been partnered with the program since 2017 and can opt into a profit-sharing deal before the Phase 3 study, but has yet to make a decision, according to De Backer. Despite swapping much of its infectious disease work for a trio of early-stage cancer products earlier this year, De Backer says Vir is ready to commercialize the combo should it be successful in Phase 3. “It’s sort of the ideal size of an opportunity; it’s not too small, it’s not too big,” she said. “You can really identify where the patients are.” Both Vir and Bluejay boasted clean safety profiles. Vir said there were no treatment-related discontinuations in the combination arm and that no treatment-related serious adverse events were reported. Bluejay had similar safety data and said that no side effects were grade 3 or higher. Both companies are looking to surpass Gilead after its US rejection two years ago, citing concerns with its “ manufacturing and delivery .” The drug is marketed as Hepcludex abroad. At the time, Gilead said it was working to bring the drug to patients “as soon as possible.” But a Gilead spokesperson said that the company has not yet re-filed and is still “working with regulatory authorities on a potential path forward.” Revenue for the product is grouped in with “other liver disease” treatments in Gilead’s earnings, which has totaled $148 million in European revenue through the first nine months of 2024, up from $112 million through the first nine months of 2023.