Novavax, Inc. · NASDAQ:NVAX
Novavax — Technical Presentation (August 2019)
18 slides from Novavax's technical presentation, Aug 8, 2019
Slide 1: Safety of Third Trimester Immunization with an RSV F Protein Vaccine
Safety of Third Trimester Immunization with a Respiratory Syncytial Virus (RSV) F Protein Vaccine and Protection of Infants over the First 180 Days of Life Against All-Cause Lower Respiratory Tract Infection Geeta K. Swamy, MD Duke University, Durham, NC, USA G.K. Swamy, F.M. Munoz, F. Polack, S.A.
Slide 2: Disclosures
Disclosures • Novavax • Site investigator for the study • Unpaid consultant for protocol design • GlaxoSmithKline • Chair, Independent Data Monitoring Committee for RSV vaccine studies in pregnant women • Pfizer • Chair, Independent Data Monitoring Committee for GBS vaccine studies in pregnant women
Slide 3: Lower Respiratory Tract Infection in Infants
Lower Respiratory Tract Infection in Infants • Acute lower respiratory tract infections (LRTI) are a major source of morbidity and mortality in infants and young children worldwide.1 • LRTI due to respiratory syncytial virus (RSV) is: • The second leading cause of infant death worldwide2; and • the
Slide 4: Maternal Immunization to Address Infant LRTI
Maternal Immunization to Address Infant LRTI • Young age at infection is the most significant factor predicting severity of acute LRTI1, probably due to: • Small caliber airways • Immature immune system • Achieving timely immunity via active immunization in the first few months of life is challengin
Slide 5: The RSV F Nanoparticle Vaccine Trial: Study Design
The RSV F Nanoparticle Vaccine Trial: Study Design Determine the efficacy of maternal immunization with the RSV F vaccine against Primary medically significant RSV lower respiratory tract infection (LRTI) through 90, 120, 150 objective and 180 days of life in infants. Randomized, Observer-Blind, Pla
Slide 6: Demography of the Enrolled Women
Demography of the Enrolled Women • Inclusion/exclusion criteria dictated a low-risk pregnancy population • Age: Global mean (SD) = 26 (5.2) yr; median = 26 yr • Approx. 2/3 of mothers in the 18 - <29 yr stratum, well-balanced • Race/Ethnicity: • 30.1% white • 43.6% black/African • 26.2% all other •
Slide 7: Safety Outcomes
Safety Outcomes • Short-term vaccine reactogenicity: 57% of vaccinees vs. 41.3% in placebo group, • Primary drivers are mild injection site pain and swelling, <1% persists beyond 7 days • Minimal difference in systemic reactogenicity, no increase in fever in the 7 days post-treatment (1.2% vaccines
Slide 8: Pregnancy and Delivery Outcomes
Pregnancy and Delivery Outcomes Event type, n of subjects with event (%) Placebo (N = 1582) RSV F Vaccine (N = 3047) Total (N = 4629) New or worsened gestational diabetes 5 (0.3) 5 (0.2) 10 (0.2) Gestational hypertension 68 (4.3) 141 (4.6) 209 (4.5) Pre-eclampsia 42 (2.7) 72 (2.4) 114 (2.5) Eclampsi
Slide 9: Infant Birth Outcomes
Infant Birth Outcomes Placebo (n = 1562) RSV F Vaccine (n = 3010) Total (n = 4572) Male/female* 51.2%/48.5% 51.7%/48.2% 51.5%/48.3% Gestational age (weeks) at delivery* Mean (SD) 39.3 (1.58) 39.3 (1.49) 39.3 (1.52) Median 39.4 39.4 39.4 ≥37 weeks, n (%) 1459 (93.4) 2813 (93.5) 4272 (93.4) <37 weeks
Slide 10: Anti-RSV F Protein IgG: Screen through Day 180 After Delivery
Anti-RSV F Protein IgG: Screen through Day 180 After Delivery in Women and Infants Seroresponse rates in vaccinees = 98.3% Geo. mn. cord serum/maternal serum 1.17 (1.19, 1.14) 4-fold rise in vaccinees = 91.9% T1/2 = 38.3 days in active vaccine infants
Slide 11: Effect of Immunization Timing on Transplacental Antibody Transfer
Effect of Immunization Timing on Transplacental Antibody Transfer Gestational Age at Immunization Interval from Immunization to Delivery <33 weeks ≥33 weeks 14 to <30 days ≥30 days Transfer of anti-F IgG 138% (135, 141) 91% (88, 94) 66% (63, 70) 127% (125, 130) Transfer of PCA* 122% (119, 124) 83% (
Slide 12: Impact of Maternal Immunization on Medically-Significant LRTI through 90 Days
Impact of Maternal Immunization on Medically- Significant LRTI through 90 Days of Life • Medically-significant LRTI required lower tract findings, SpO2 <95% or tachypnea ≥70bpm under 2 mos., ≥60bpm at ≥ 2mos. Per-Protocol Intent-to-Treat Placebo Vaccine Efficacy Placebo Vaccine Efficacy N = 1430 N =
Slide 13: Impact on LRTI with Severe Hypoxemia through 90 Days of Life
Impact of Maternal Immunization on LRTI with Severe Hypoxemia through 90 Days of Life • Severe hypoxemia requires SpO2 <92% or advanced O2 support (high-flow nasal cannula, helium/oxygen, CPAP, mechanical ventilation. Per-Protocol Intent-to-Treat Placebo Vaccine Efficacy Placebo Vaccine Efficacy N =
Slide 14: Impact on LRTI Precipitating Hospitalization through 90 Days of Life
Impact of Maternal Immunization on LRTI Precipitating Hospitalization through 90 Days of Life Per-Protocol Intent-to-Treat Placebo Vaccine Efficacy Placebo Vaccine Efficacy N = 1430 N = 2765 (95%CI) N = 1547 N = 2980 (95%CI) RSV LRTI with hospitalization 53 57 44% 60 60 48% Days 0 to 90 (20, 62) (26
Slide 15: Durable Efficacy Against More Severe Disease, Including All-cause Pneumonia
Durable Efficacy Against More Severe Disease, Including All-cause Pneumonia • Unsurprisingly, efficacy wanes as maternal antibody is cleared, • Net efficacy against RSV LRTI with severe hypoxemia or hospitalization is relatively well-maintained (>40% through 180 days). • An impact on all-cause clini
Slide 16: Impact of Maternal RSV Immunization on Pneumonia over One Year of Life
Impact of Maternal RSV Immunization on Pneumonia over One Year of Life Counts (%) • Clear post-hoc Endpoint Time Interval Placebo Vaccine Efficacy 95% CI observation of efficacy (N = 1562) (N = 3010) against infant pneumonia Clinical pneumonia 0 to 90 days 51 (3.27) 45 (1.50) 54.2% 32.0, 69.2 throug
Slide 17: Conclusions (1)
Conclusions (1) • 4,636 maternal – infant pairs were studied across 3.5 years and 11 countries. • The RSV F vaccine was well-tolerated by pregnant women. • No meaningful changes in the overall safety profile were noted in the women or their infants through 180 days post-delivery. • 364 day safety fo
Slide 18: Conclusions (2)
Conclusions (2) • Observed efficacy of the vaccine strategy was 39.4% against the primary endpoint, medically-significant RSV LRTI, but… • Observed efficacy was greater against more severe endpoints: RSV LRTI with severe hypoxemia and RSV LRTI with hospitalization. • Efficacy against all pneumovirus