Item 8.01 Other Events.
Continuing Progress of the
plc ("GSK") issued a press release announcing final, confirmatory results from
the Phase 3 COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial - Intent to
Care Early) trial demonstrating that sotrovimab, an investigational SARS-CoV-2
monoclonal antibody, significantly reduced the risk of hospitalization or death
among high-risk adult outpatients with mild-to-moderate COVID-19.
The primary efficacy analysis of all 1,057 patients in the COMET-ICE trial
demonstrated a 79% reduction (adjusted relative risk reduction) (p<0.001) in
hospitalization for more than 24 hours or death due to any cause, by Day 29
compared to placebo, meeting the primary endpoint of the trial.
The number of patients in the trial who were hospitalized for >24 hours for
acute management of any illness or death from any cause at Day 29 was six
patients in the sotrovimab arm (1%), versus 30 patients in the placebo arm (6%).
In the sotrovimab arm, it is possible that half of those patients who were
hospitalized were for reasons other than progression of COVID-19 (e.g., small
bowel obstruction, lung cancer and diabetic foot ulcer); this was not the case
for patients in the placebo arm. In the safety analysis, 1,037 participants were
followed through at least 29 days. The most common adverse events observed in
the sotrovimab treatment group in COMET-ICE were rash (1%) and diarrhea (2%),
all of which were Grade 1 (mild) or Grade 2 (moderate). No other
treatment-emergent adverse events were reported at a higher rate with sotrovimab
compared to placebo. The Company and GSK plan to submit the full COMET-ICE data
set to a peer-reviewed journal for publication.
regarding the emergency use authorizations of anti-SARS-CoV-2 monoclonal
antibodies for the treatment of COVID-19 in the
sotrovimab for non-hospitalized patients with mild-to-moderate COVID-19 who are
at high risk of clinical progression. The guidelines note that the target
binding site of sotrovimab is in a region of the virus that does not overlap
with the binding site location of key mutations in current variants of concern
and interest. These guidelines were based upon an interim analysis of 583
patients in the COMET-ICE trial, which was stopped early in
independent data monitoring committee because interim results demonstrated
evidence of sotrovimab's clinical efficacy. The interim study results
demonstrated an 85% (p=0.002) reduction in hospitalization for more than 24
hours or death in those receiving sotrovimab compared to placebo, the primary
endpoint of the trial.
These data have informed global regulatory reviews to date, including the
positive scientific opinion issued by the
Committee for Human Medicinal Products ("CHMP") under Article 5(3) of Regulation
726/2004, as well as the Emergency Use Authorization ("EUA") granted by the
Food and Drug Administration
The Company and GSK are actively working with government agencies around the
world to make sotrovimab available to patients in need of treatment. The Company
and GSK plan to submit a Biologics License Application to the FDA in the second
half of 2021. The EMA has started a rolling review of data on sotrovrimab that
will continue until enough evidence is available to support the filing of a
formal marketing authorization application. The Company and GSK also announced
that their strategic manufacturing network is enabling the manufacture of
approximately two million doses to support emergency supply in the first year
following EUA, with approximately 450,000 doses on hand.
The Company and GSK also announced continued progress with the robust COMET
clinical development program, which aims to provide clinical evidence from
several studies over the course of the next year.
• COMET-PEAK, a pharmacokinetic study in outpatients with mild-to-moderate
COVID-19 investigating intramuscular (IM) administration of sotrovimab,
is near completion and initial data is expected in second half of 2021.
• COMET-TAIL has been initiated. This is a Phase 3 study evaluating the
role of IM-administered sotrovimab for the early treatment of
mild-to-moderate COVID-19 in high-risk non-hospitalized adult and
pediatric patients (12 years of age and older). Data are anticipated in
the first half of 2022.
• A prophylaxis study is planned in uninfected immunocompromised adults to
determine whether IM-administered sotrovimab can prevent symptomatic
New Clinical Data from Ongoing Trials of VIR-2218 and VIR-3434
its ongoing Phase 2 clinical trials of VIR-2218 and ongoing Phase 1 studies of
VIR-3434 in patients with chronic hepatitis B virus ("HBV") infection. The
results, which demonstrate positive safety findings plus a reduction in
hepatitis B surface antigen ("HBsAg") for both compounds, were presented in two
oral and two poster presentations at the
In summary, data presented this week demonstrate the promising safety profile
and potential durable response of VIR-2218, an investigational small interfering
ribonucleic acid ("siRNA") that mediates RNA interference ("RNAi"), through 48
weeks. In a separate analysis evaluating VIR-2218 in combination with pegylated
interferon alfa ("PEG-IFN-?") for 12 weeks, a more rapid and substantial HBsAg
decline was observed in the co-administration cohort compared to VIR-2218 alone.
The treatment regimen resulted in no new safety signals.
Additionally, two new analyses from an ongoing Phase 1 trial of VIR-3434 showed
no safety signals in healthy volunteers dosed with up to 3,000 mg, and a rapid
reduction in HBsAg levels one week after subcutaneous administration of this
investigational HBV-neutralizing monoclonal antibody, which has been Fc
engineered to include the XX2 "vaccinal mutation," allowing it to potentially
function as a T cell vaccine.
VIR-2218 Key Data
Results from a Phase 2 multiple-ascending dose trial of VIR-2218 in 32 patients
with chronic HBV infection evaluating the safety and antiviral activity of two
doses of VIR-2218 (20 to 200 mg) administered subcutaneously four weeks apart
• Dose-dependent reductions in HBsAg through 48 weeks in both trial
participants with hepatitis B e antigen ("HBeAg"), a marker of actively
replicating HBV, and those without.
• Of the 12 participants who received the 100 mg or 200 mg dose, four
participants experienced sustained HBsAg reductions of >1 log10 IU/mL and
absolute HBsAg levels below 100 IU/mL through Week 48.
• Treatment with VIR-2218 also achieved dose-related reductions in other
viral biomarkers; one patient receiving 200 mg experienced HBeAg loss at
Week 24 and anti-HBe seroconversion at Week 16 that was sustained through
• Adverse events were mild, and no dose-dependent changes in post-treatment
ALT levels (a signal of liver damage) occurred. No trial participants
In a separate ongoing Phase 2 trial, 47 adult patients with chronic HBV
infection were assigned to receive subcutaneously injected VIR-2218 alone or in
combination with PEG-IFN-?. Preliminary results through Week 12 of the treatment
• VIR-2218 alone and in combination with PEG-IFN-? were associated with
HBsAg reductions of >1 log10 IU/mL by Week 12.
• Co-administration of VIR-2218 with PEG-IFN-? ("Cohort 3") resulted in a
more rapid and substantial HBsAg decline compared to VIR-2218 alone.
• In Cohort 3, the mean HBsAg decline from baseline was 2.0 log10 IU/mL at
Week 12 and 0.6 log10 IU/mL greater than in the two cohorts evaluating
• In published studies, PEG-IFN? alone in virally suppressed patients was
associated with £ 0.25 log10 IU/mL HBsAg decline, on average, over the
first 12 weeks.
• No treatment-related grade ³3 treatment-emergent adverse events or
serious adverse events were reported with VIR-2218 alone or in
combination with PEG-IFN-?, and the combination did not appear to
increase the known side effects of PEG-IFN-?.
VIR-3434 Key Data
Results from a Phase 1 trial evaluating VIR-3434 in 40 virally suppressed
patients with chronic HBV infection who were randomized to receive a single low
dose of either 6 mg or 18 mg for four weeks demonstrate:
• Treatment with VIR-3434 resulted in rapid >1 log10 IU/mL reductions in
HBsAg, with the largest reductions (>1.5 log10 IU/mL) observed in the 18
mg cohort; maximum reductions were generally observed within one week.
• No new safety signals were identified with single doses of VIR-3434; all
adverse events were grade 1 or 2.
• No significant changes in liver-related laboratory parameters or
clinically significant changes in ALT or other liver-related laboratory
parameters were reported.
In a separate Phase 1 trial in 40 healthy adult volunteers evaluating single
doses of up to 3,000 mg of VIR-3434 administered subcutaneously or
intravenously, results demonstrate:
• Subcutaneous administration of VIR-3434 showed favorable pharmacokinetic
properties, with VIR-3434 remaining in the serum for 24 weeks.
• No new safety signals were identified; specifically, no grade 3/4 adverse
events, serious adverse events or adverse events leading to trial
discontinuation were reported.
Sotrovimab Variant Update
Data from in vitro studies, published in bioRxiv has been updated to include new
in vitro data demonstrating that sotrovimab retains activity against the
following variants: Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), Epsilon
(B.1.427/B.1.429), Gamma (P.1), Iota (B.1.526) and Kappa (B.1.617.1), as well as
a new variant from Bristol (B.1.1.7+E484K) and the new variant from
(B.1.619), which encodes both N440K and E484K mutations that may lead to reduced
activity for other antibody products. The Company and GSK are continuing to
evaluate the ability of sotrovimab to maintain activity against new and emerging
variants through in vitro studies. The clinical impact of this in vitro variants
data is not yet known.
EASL ILC 2021 Hepatitis B Data Presentation
presentation to its website. A copy of the presentation is attached as Exhibit
This Current Report on Form 8-K contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995. Words such as
"may," "will," "plan," "potential," "aim," "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 the Company's expectations and
assumptions as of the date of this Current Report on Form 8-
statements contained in this Current Report on Form 8-K include, but are not
limited to, statements regarding the final data from the COMET-ICE trial,
guidelines recommending the use of sotrovimab in the treatment of COVID-19, the
initiation of the Company's COMET-TAIL clinical trial, the clinical development
program for sotrovimab, the Company's capacity to manufacture and supply
sotrovimab, the ability of sotrovimab to treat and/or prevent COVID-19, the
ability of sotrovimab to maintain activity against circulating variants of
concern, statements regarding clinical data from the Company's ongoing trials of
VIR-2218 and VIR-3434, timing of the Phase 2 trial of VIR-3434 in combination
with VIR-2218, the ability of VIR-2218 and VIR-3434 (as monotherapies or
combination therapies) to treat and/or prevent chronic HBV infection, and
statements related to regulatory authorizations and approvals, including plans
and discussions with the FDA, EMA and other global regulators. Many factors may
cause differences between current expectations and actual results, including
unexpected safety or efficacy data observed during preclinical or clinical
studies, challenges in the treatment of hospitalized patients, difficulties in
collaborating with other companies or government agencies, challenges in
accessing manufacturing capacity, successful development and/or
commercialization of alternative product candidates by the Company's
competitors, changes in expected or existing competition, delays in or
disruptions to the Company's business or clinical trials due to the COVID-19
pandemic, geopolitical changes or other external factors, and unexpected
litigation or other disputes. 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 the Company's filings with the
and Exchange Commission
therein. Except as required by law, the Company assumes no obligation to update
any forward-looking statements contained herein to reflect any change in
expectations, even as new information becomes available.
Item 9.01 Financial Statements and Exhibits.
99.1 Presentation, dated
104 Cover Page Interactive Data File (embedded within the Inline XBRL document)
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