Item 8.01 Other Events.
Continuing Progress of the
On
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.
The
These data have informed global regulatory reviews to date, including the
positive scientific opinion issued by the
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 COVID-19 infection.
--------------------------------------------------------------------------------
New Clinical Data from Ongoing Trials of VIR-2218 and VIR-3434
On
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 demonstrate:
• 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 Week 48. • Adverse events were mild, and no dose-dependent changes in post-treatment ALT levels (a signal of liver damage) occurred. No trial participants discontinued treatment.
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 period demonstrate:
• 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 VIR-2218 alone. • 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
EASL ILC 2021 Hepatitis B Data Presentation
On
Forward-Looking Statements
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-
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits Exhibit No. Description 99.1 Presentation, datedJune 25, 2021 . 104 Cover Page Interactive Data File (embedded within the Inline XBRL document)
--------------------------------------------------------------------------------
© Edgar Online, source