Candidates: VIR-7831 (also known as GSK4182136) and VIR-7832 (antibodies); future vaccines and functional genomics products targeting SARS-CoV-2, and potentially other coronaviruses.
Types: Antiviral antibodies based on Vir’s proprietary monoclonal antibody platform technology; Vaccines based on GSK’s vaccine technologies; Functional genomics products based on genome-wide CRISPR screening of host targets expressed in connection with exposure to SARS-CoV-2, and potentially other coronaviruses.
2021 Status: Researchers for Vir and the University of Washington on April 1 published preclinical research in bioRxiv in which VIR-7831 was shown to maintain its neutralizing activity against a mutation in the receptor binding domain (RBD) of SARS-CoV-2, called L452R, found in the California variant (B.1.427/B.1.429). The study also showed that the L452R mutation reduced both the neutralization potency of plasma from vaccinated and convalescent donors and the neutralization activity of 14 RBD-specific and 10 N-terminal domain (NTD)-specific monoclonal antibodies, including three clinical-stage monoclonal antibodies.
Researchers characterized the impact of L452R’s three mutations: S13I and W152C in the NTD and L452R in the RBD. Data from 43 vaccinated donors and nine convalescent donors showed that, in a pseudotyped virus system, the S13I, W152C and L452R mutations reduced the neutralization potency of plasma by three-to-six-fold. In addition, the L452R mutation reduced the neutralization activity of 14 out of 35 RBD-specific mAbs, including three clinical-stage antibodies. Researchers also reported a complete loss of neutralization by all NTD-specific monoclonal antibodies that is mediated by an unconventional escape mechanism. VIR-7831, which targets a non-receptor binding motif epitope, was unaffected by the L452R mutation.
The data has been submitted to a peer-reviewed journal for future print publication, Vir said.
Vir and GSK said March 10 that they plan to apply for FDA emergency use authorization (EUA) and similar authorizations in other countries for VIR-7831, based on positive results from their Phase III COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early) trial (NCT04545060). The trial’s Independent Data Monitoring Committee (IDMC) recommended the study stop enrolling patients due to evidence of “profound” efficacy. The companies cited an interim analysis of data from 583 patients enrolled in the COMET-ICE trial, showing an 85% reduction in hospitalization or death in patients receiving VIR-7831 as monotherapy compared to placebo, the primary endpoint of the trial. VIR-7831 was well tolerated.
The trial remains ongoing and blinded with patients continuing to be followed for 24 weeks. Additional results, including epidemiology and virology data, will be forthcoming once the trial is completed, Vir and GSK said.
COMET-ICE is one of four “COMET” trials comprising the companies’ clinical development program for VIR-7831. The other three:
- COMET-PEAK: An ongoing Phase II trial with two parts: to compare the safety and viral kinetics of 500 mg intramuscularly (IM) administered VIR-7831 to 500 mg intravenously administered VIR-7831 among low-risk adults with mild to moderate COVID-19 and to evaluate the similarity in pharmacokinetics between VIR-7831 manufactured by different processes.
- COMET-TAIL: A Phase III trial expected to begin in the second quarter in high-risk adults to assess whether IM-administered VIR-7831 can reduce hospitalization or death due to COVID-19.
- COMET-STAR: A Phase III trial expected to begin in the second quarter in uninfected adults at high risk to determine whether IM-administered VIR-7831 can prevent symptomatic infection.
Vir joined Eli Lilly and GlaxoSmithKline (GSK) on January 27 to say that Lilly’s bamlanivimab 700 mg is being studied in combination with Vir/GSK’s VIR-7831 (GSK4182136), 500 mg, in an expansion of the ongoing, 700-participant BLAZE-4 trial (NCT04634409), which the companies said marks the first time that monoclonal antibodies from separate companies will be brought together to explore potential outcomes. The neutralizing antibodies bind to different epitopes of the SARS-CoV-2 spike protein.
2020 Status: 2020 Status: Vir and GSK said August 31 that the first patient was dosed last week in the Phase II/III COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early) study, designed to evaluate whether VIR-7831, as a single-dose monoclonal antibody, can prevent hospitalization in patients with mild or moderate forms of COVID-19 who are at high risk of progression to severe disease, such as the elderly or those with pre-existing conditions such as lung or heart disease.
COMET-ICE will consist of a Lead-In phase that will assess the safety and tolerability of a single 500 mg intravenous (IV) infusion of VIR-7831 or placebo over a 14-day period in non-hospitalized patients. It aims to recruit 20 patients across the U.S. The Expansion phase will assess the safety and efficacy of a single IV infusion of VIR-7831 or placebo in approximately 1,300 non-hospitalized participants globally.
The primary efficacy endpoint is the proportion of patients with mild or moderate COVID-19 who worsen, as defined by the need for hospitalization or death, within 29 days of randomization. Initial results from COMET-ICE may be available before the end of 2020, with complete results expected in the first quarter of 2021, Vir and GSK said. Patients could potentially access the antibody treatment as soon as the first half of 2021, the companies added.
Vir and GSK disclosed that the clinical development program for VIR-7831 includes two additional planned trials—one for the treatment of severely ill hospitalized patients and another for the prophylaxis of symptomatic infection.
As for VIR-7832, Vir and GSK said they expect to start a Phase II of the neutralizing monoclonal antibody, which shares the same characteristics as VIR-7831 but may also function as a therapeutic and/or prophylactic T cell vaccine.
On June 15, Vir disclosed in a regulatory filing that six days earlier, it formalized an exclusive collaboration agreement with GSK to research, develop, and commercialize products for the prevention, treatment and prophylaxis of diseases caused by SARS-CoV-2, and potentially other coronaviruses.
For four years following the agreement’s April 29 effective date, subject to rights granted to WuXi Biologics under agreements with Vir, GSK and Vir will have exclusive research collaborations covering antibody products directed to SARS-CoV-2 or any other coronavirus, as well as functional genomics CRISPR screens for drug discovery and development in connection with SARS-CoV-2 or other coronaviruses.
Vir is primarily responsible for development and clinical manufacturing activities for the antibody program, and for initial development activities directed to a vaccine. GSK will be primarily responsible for commercialization activities for the antibody program (except in connection with sales of antibody products licensed to WuXi in greater China), the later-stage development, manufacturing and commercialization activities for the vaccine program and the development, manufacturing and commercialization activities for the functional genomics program.
The companies agreed to share all development costs, manufacturing costs and costs and expenses for the commercialization of the collaboration products, with Vir bearing 72.5% of such costs for the antibody products, 27.5% of such costs for the vaccine products, and the parties sharing equally all such costs for the functional genomics products.
In April, GSK agreed to make a $250 million equity investment in Vir under an R&D collaboration designed to advance COVID-19 candidates into Phase II clinical trials later this year,. The companies agreed to identify new anti-viral antibodies, and study existing ones, to prevent and treat COVID-19 and future coronaviruses.
GSK and Vir also agreed to research vaccines designed to prevent SARS-CoV-2 and other coronaviruses, as well as combine their expertise in CRISPR screening and artificial intelligence to identify products based on genome-wide CRISPR screening of host targets expressed in connection with exposure to SARS-CoV-2.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: