Slide 1: Phase III CENTERSTONE trial of single-dose baloxavir marboxil for reduction of influenza transmission
Phase III CENTERSTONE trial of single-dose baloxavir marboxil for the reduction of transmission of influenza in households Arnold S Monto1, Klaus Kuhlbusch2, Corrado Bernasconi2*, Bin Cao3, Svetoslav Dachev4, Herman Avner Cohen5, Aeron C Hurt2, Emily Graham6, Laurie Katugampola6, Takashi Kamezawa7,
Slide 2: Disclosures
Disclosures ▪ BJC has received honoraria from AstraZeneca, BioNTech, Fosun Pharma, GSK, Haleon, Moderna, Novavax, Roche and Sanofi Pasteur 2
Slide 3: Influenza poses a major and ongoing burden to global public health
Influenza poses a major and ongoing burden to global public health ▪ Seasonal influenza results in up to 1 billion cases and 650,000 deaths worldwide each year despite annual vaccination of at-risk individuals; in addition, pandemics remain an ever-present threat ▪ Limiting the spread of influenza v
Slide 4: Baloxavir marboxil has been evaluated for reduction of onward transmission
The antiviral baloxavir marboxil has been evaluated for the reduction of onward transmission of influenza virus ▪ Baloxavir marboxil, administered as a single oral dose, is a selective inhibitor of influenza virus cap-dependent endonuclease and is approved for treatment of uncomplicated influenza in
Slide 5: CENTERSTONE: a Phase IIIb, randomised, placebo-controlled transmission trial
CENTERSTONE: a Phase IIIb, randomised, placebo-controlled transmission trial in OwH IPs NCT03969212 Day 0/1 HHC screening (≤24 hours) Days 1–4 Day 5†‡ Days 6–8 Day 9‡ IPs HHCs Unscheduled Nurse visit Unscheduled Nurse visit ▪ Aged ≥5 to ≤64 years 1 Baloxavir ▪ Aged ≥2 years visit to swab to swab vis
Slide 6: The primary endpoint was transmission of influenza virus by Day 5
The primary endpoint was transmission of influenza virus by Day 5 Primary endpoint: transmission of influenza virus by Day 5 Proportion of RT-PCR–positive HHCs by Day 5 following IP treatment, with a virus subtype consistent with that of the IP *Additional secondary efficacy endpoints were evaluated
Slide 7: The primary endpoint was transmission of influenza virus by Day 5
The primary endpoint was transmission of influenza virus by Day 5 Primary endpoint: transmission of influenza virus by Day 5 Proportion of RT-PCR–positive HHCs by Day 5 following IP treatment, with a virus subtype consistent with that of the IP Secondary efficacy endpoints* Transmission of influenza
Slide 8: The primary endpoint was transmission of influenza virus by Day 5
The primary endpoint was transmission of influenza virus by Day 5 Primary endpoint: transmission of influenza virus by Day 5 Proportion of RT-PCR–positive HHCs by Day 5 following IP treatment, with a virus subtype consistent with that of the IP Secondary efficacy endpoints* Transmission of influenza
Slide 9: A total of 1457 IPs were randomised
A total of 1457 IPs were randomised Disposition of participants in the “full analysis set” of index patients (FAS-IP*) and household contacts (FAS-HHC†) Randomised (FAS-IP) N=1457 Placebo Baloxavir N=731 N=726 IPs Received treatment Received treatment N=727 N=722 PAS-IP PAS-IP N=544 N=548 Completed
Slide 10: Demographics and baseline characteristics among IPs were generally well balanced
Demographics and baseline characteristics among IPs were generally well balanced between treatment arms PAS-IP population Placebo (N=544) Baloxavir (N=548) Mean age, years (SD) 31.8 (15.9) 30.8 (15.2) Aged ≥5 to <12, n (%) 46 (8.5) 44 (8.0) Aged ≥12 to ≤30, n (%) 235 (43.2) 245 (44.7) Aged >30, n (%
Slide 11: Demographics and baseline characteristics among IPs (cont'd)
Demographics and baseline characteristics among IPs were generally well balanced between treatment arms (cont’d) PAS-IP population Placebo (N=544) Baloxavir (N=548) Influenza virus type, n (%) A* 451 (82.9) 450 (82.1) B† 91 (16.7) 93 (17.0) A and B 2 (0.4) 5 (0.9) Influenza A virus subtype, n (%) N=
Slide 12: Demographics and baseline characteristics among HHCs were generally well balanced
Demographics and baseline characteristics among HHCs were generally well balanced between treatment arms IP allocation PAS-HHC population Placebo (N=1098) Baloxavir (N=1118) Mean age, years (SD) 35.1 (18.3) 35.4 (18.6) Aged ≥2 to <12, n (%) 118 (10.7) 121 (10.8) Aged ≥12, n (%) 980 (89.3) 997 (89.2)
Slide 13: Baloxavir showed a significant reduction in transmission of influenza virus by Day 5
Baloxavir showed a statistically significant and clinically meaningful reduction in transmission of influenza virus by Day 5 compared with placebo Transmission of influenza virus by Day 5* IPs HHCs Placebo arm IP Adjusted incidence of transmission N=544 13.4% 29% aRRR with baloxavir (N=1098 HHCs) (9
Slide 14: Baloxavir showed a significant reduction in transmission by Day 5 and Day 9
Baloxavir showed a statistically significant and clinically meaningful reduction in transmission of influenza virus by Day 5 compared with placebo Transmission of influenza virus by Day 5* IPs HHCs Placebo arm IP Adjusted incidence of transmission N=544 13.4% 29% aRRR with baloxavir (N=1098 HHCs) (9
Slide 15: A consistent directional transmission benefit was observed across all subgroups
A consistent directional transmission benefit was observed with baloxavir across all subgroups Transmission of influenza virus by Day 5* IP allocation Placebo Baloxavir Baseline characteristics N N (% positive) N (% positive) aOR 95.38% CI All HHCs 2216 1098 (13.42) 1118 (9.50) 0.68 0.50–0.93 IP inf
Slide 16: Consistent directional transmission benefit across all subgroups (cont'd)
A consistent directional transmission benefit was observed with baloxavir across all subgroups (cont’d) Transmission of influenza virus by Day 5* IP allocation Placebo Baloxavir Baseline characteristics N N (% positive) N (% positive) aOR 95.38% CI All HHCs 2216 1098 (13.42) 1118 (9.50) 0.68 0.50–0.
Slide 17: The key secondary efficacy endpoint was transmission resulting in symptoms by Day 5
The key secondary efficacy endpoint was transmission of influenza virus resulting in symptoms by Day 5 Primary endpoint: transmission of influenza virus by Day 5 Proportion of RT-PCR–positive HHCs by Day 5 following IP treatment, with a virus subtype consistent with that of the IP Secondary efficacy
Slide 18: Clinically meaningful reduction in transmission resulting in symptoms, significance not reached
Baloxavir showed a clinically meaningful reduction in transmission of influenza virus resulting in symptoms, but statistical significance was not reached Transmission of influenza virus resulting in symptoms by Day 5* IP allocation Placebo Baloxavir Baseline characteristics N N (% positive) N (% pos
Slide 19: Reduction in symptomatic transmission, significance not reached (cont'd)
Baloxavir showed a clinically meaningful reduction in transmission of influenza virus resulting in symptoms, but statistical significance was not reached (cont’d) Transmission of influenza virus resulting in symptoms by Day 5* IP allocation Placebo Baloxavir Baseline characteristics N N (% positive)
Slide 20: Baloxavir was well tolerated and no new safety signals were identified
Baloxavir was well tolerated and no new safety signals were identified Safety IP population Placebo (N=726) Baloxavir (N=723)* IPs with ≥1 AE, n (%) 51 (7.0) 33 (4.6) Total AEs, n 75 36 IPs with ≥1 AE related to treatment, n (%) 6 (0.8) 4 (0.6) IPs with ≥1 AE by MedDRA SOC, n (%)† Infections and inf
Slide 21: No cases of resistance-associated substitutions were observed in HHCs
No cases of resistance-associated substitutions (RAS) were observed in HHCs ▪ No viruses with RAS were detected in IPs at baseline ▪ The rate of treatment-emergent RAS in IPs was 7.2% (95% CI, 4.1–11.6%), consistent with previous trials, and transmission of viruses with RAS was not detected in any o
Slide 22: CENTERSTONE is the first global Phase III RCT to demonstrate antiviral transmission benefit
CENTERSTONE is the first global Phase III RCT to demonstrate a benefit for an antiviral in reducing onward transmission of influenza viruses ▪ Baloxavir treatment resulted in a statistically significant and clinically meaningful reduction in transmission of influenza virus from IPs to HHCs by Day 5
Slide 23: Acknowledgements
Acknowledgements ▪ All patients and investigators who participated in the trial ▪ This project has been funded by F. Hoffmann-La Roche Ltd and with federal funds from the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Researc