Development of a heat-stable Rotavirus vaccine using innovative delivery technology

Transcription

1 Development of a heat-stable Rotavirus vaccine using innovative delivery technology 1

2 HILLEMAN OPERATING MODEL IS UNIQUE WITH FOCUS ON TRANSLATIONAL SCIENCE AND GETTING AFFORDABLE VACCINES TO MARKET FASTER Headquartered in New Delhi, we function as a biotech company translating our innovation into important vaccine products. Our focus is on transforming ideas into products through translational R&D and by building partnerships with vaccine manufacturers Sustainability for funding Hilleman Lab s R&D Founding contribution from MSD and Wellcome Trust Licensing and Royalty payments Raising project specific funding Grants Innovative financing Maurice Hilleman To date, our focus has been largely on Vaccines and Infectious Disease and opportunities that meet the unmet needs of the developing world 2

3 HILLEMAN WAS TARGETING DEVELOPMENT OF A HEAT STABLE ROTAVIRUS VACCINE Parameter Description Product Description Live oral pentavalent lyophilized vaccine with diluent for the prevention of rotavirus gastroenteritis Indication Indicated for the prevention of rotavirus gastroenteritis caused by serotypes contained in the vaccine Target Population Indicated for infants between the ages of 6 to 32 weeks Administration 3 doses administered orally starting at 6 to 12 weeks of age, with the subsequent doses administered at 4- to 10-week intervals Formulation Supplied in two chambered Integrated Reconstitution and Administration Device as a single dose powder with 2 ml liquid buffer Storage Room temperature away from direct sunlight Safety/ Tolerability Similar to RV5 (pentavalent rotavirus vaccine) Efficacy Immunobridging to RV5 (pentavalent rotavirus vaccine) 3

4 PHASE I STUDY DEMOGRAPHICS: ADULTS Study Design Randomized Phase I/II, two cohort sequential study (n=50 each) Cohort I: Adults, doubleblinded, HSRV or Placebo (1:1) single oral dose for safety Cohort II: Infants (6-8 weeks old), HSRV or RotaTeq (1:1) 3-dose series (oral) for safety (open-labeled) and immunogenicity (blinded) Study Location icddr, Bangladesh Characteristic HSRV Vaccine Placebo All Category Statistic (N = 26) (N = 24) (N = 50) Age (years) at vaccination N Gender Race Adult cohort Mean SD Median Minimum Maximum Male n (%) 11 (42.3) 11 (45.8) 22 (44.0) Female n (%) 15 (57.7) 13 (54.2) 28 (56.0) Asian n (%) 26 (100) 24 (100) 50 (100) Study Period June April 2017 Abbreviations: HSRV = Heat-stable rotavirus vaccine; N = Number of participants in the treatment arm; n = Number of participants in the specific category; SD = standard deviation. Note: % was calculated using the number of participants in the treatment arm as the denominator (n/n*100). Cohort I Data Presented at the Twelfth International Rotavirus Symposium

5 PHASE I STUDY DEMOGRAPHICS: INFANTS Study Design Randomized Phase I/II, two cohort sequential study (n=50 each) Cohort I: Adults, doubleblinded, HSRV or Placebo (1:1) single oral dose for safety Cohort II: Infants (6-8 weeks old), HSRV or RotaTeq (1:1) 3-dose series (oral) for safety (open-labeled) and immunogenicity (blinded) Study Location icddr, Bangladesh Study Period June April 2017 Infant cohort Characteristic Category Age (weeks) at vaccination Gender Male Female Race Asian Statistic N Mean SD Median Minimum Maximum n (%) n (%) HSRV Vaccine (N = 25) (36.0) 16 (64.0) RotaTeq (N = 25) (56.0) 11 (44.0) All (N = 50) (46.0) 27 (54.0) n (%) 25 (100.0) 25 (100.0) 50 (100) Abbreviations: HSRV = Heat-stable rotavirus vaccine; N = Number of participants in the treatment arm; n = Number of participants in the specific category; SD = standard deviation. Note: % was calculated using the number of participants in the treatment arm as the denominator (n/n*100). 5

6 SAFETY RESULTS: NO SERIOUS ADVERSE EVENTS WERE REPORTED IN EITHER OF THE 2 COHORTS AdultCohort Overall there were 6 (23.1% ) participants in HSRV group who reported at least one solicited Adverse Events (AE) and 2 (8.3%) in placebo group No reports of any Grade 3 symptoms All AEs (both solicited and unsolicited) were mild to moderate in intensity and resolved without any sequela None of the symptoms reported were assessed to be causally related to vaccination None of the participants experienced any SAEs and no fatal cases reported in the study. There were no safety concerns raised based on the safety data (Presented at the Twelfth International Rotavirus Symposium 2016) Infant Cohort Overall there were 28 solicited adverse events in RotaTeq and 21 in HSRV group Cough and Rhinorrhea being most common solicited events in both groups Unsolicited events : 14 events in RotaTeq group and 20 events in HSRV group All AEs (both solicited and unsolicited) were mild to moderate in intensity and resolved without any sequela None of the symptoms reported were assessed to be causally related to vaccination. None of the participants experienced any SAEs and there were no fatal cases reported in the study. Solicited AE: Protocol listed solicited symptoms reported within 7 Days after a dose administration Unsolicited AE: Protocol listed solicited symptoms reported after 7 days after a dose administration OR any other event that is not one of the Protocol listed events; reported during the study. 6

7 INFANT IMMUNOGENICITY RESULTS ALSO EXHIBITED SIMILARITY TO ROTATEQ HSRV seroconversion is similar to RotaTeq, both for 3-fold and 4-fold rise in anti-rotavirus IgA titres from baseline to post dose 3 (Table 1). Geometric mean ratio of sero-response between HSRV and RotaTeq is similar for GMT ratios (similarity criterion being GMR between 0.5 to 2) (Table 3). Table 1 Table 2 Table 3 Seroconversion GMTs (Fold rise) GMR (HSRV/RotaTeq) >3-fold (%) >4-fold (%) HSRV 22/25 (88) 21/25 (84) RotaTeq 21/25 (84) 20/25 (80)

8 RESEARCH SURVERY HIGHLIGHTED DEMAND FOR HEAT STABLE ROTAVIRUS VACCINE IN NOVEL DELIVERY DEVICE Study Objective Scope Findings Research assessment conducted in 4 Gavi countries to identify key drivers of n decisions and recommendations regarding Rotavirus vaccines for programmatic and technical feasibility Ba Bur HSRV a positive development for use in field settings Additional cold chain requirement for new gladesh Cote d Ivoire vaccine introduction considered a key challenge Dual chamber device seen as having potential value as an impact oriented innovation Lack of precedence of a novel delivery device not perceived as a concern Respondents indicated that they would support kina Faso India HSRV purchase for EPI schedule Price premium due to heat stability was supported but varied across roles and countries 8

9 MANUFACTURING PROCESS OF HEAT STABLE ROTAVIRUS VACCINE (HSRV) DEVELOPED FOR BOTH VIALS & DUAL CHAMBER DELIVERY *R.D: Rotavirus Diluent G1 G2 G3 G4 P1 R.D Bulk Lyophilized cake Condition Stability 2-8 C > 3 years 37 C ~12 month 45 C ~4 months Dispensing of raw materials Formulation Buffer tank Filtration through0.22 micron filter Formulation holding tank Filling of Prelyophilized liquid in vials/ Trays Milling of bulk lyophilized cake Lyophilization Vial lyophilized cake Condition 2-8 C Stability* > 36 months 25 C >24 months 37 C 20 months Filling in Dual chamber pouches 45 C 7 months Blending of Milled cake with blending agent (*Ref: Rational design of heat stable lyophilized rotavirus vaccine formulations (2018). Hum Vaccin Immunother. doi: / ) Stoppered and sealed Vials 9

10 TECHNOLOGY BEHIND THERMO-STABILITY AND DUAL CHAMBER DELIVERY PROMISES POTENTIAL FOR CURRENT/FUTURE ORAL VACCINES Thermal Stability Profile Novel Delivery Design Condition Stability 2-8 C > 36 month 37 C ~12 month 45 C ~ 4 month (Tray Lyophilization) Vaxipak Integrated reconstitution and administration of medication Pursuing a cost-effective oral administration of heat-stable vaccines Such a delivery device partnered with thermal stability could enhance Last Mile Coverage by making vaccine delivery more efficient and cost-effective 10

11 VAXIPAK DEEMED USER-FRIENDLY AND SUITABLE FOR VACCINE ADMINSTRATION IN SMALL SAMPLE SIZE UAT STUDY User Acceptance Study Design Observation and user feedback on device design and usage experience Post administration observations; waste disposal, safety of the infant during vaccination/ vaccine administrator Study Demographics Multiple sites in Delhi, NCR - Research institute (CDSA-THSTI), Immunization support unit (INCLEN), PHCs, Medical Research Institute, Cold chain experts (UNDP, Delhi) Healthcare staff involved in Vaccination Doctors, Vaccinators, Nurses & Social/ Health workers Limited stakeholders (n=60) Feedback Technical Heat stable nature of vaccine Need of the hour Single unit delivery device Easy to prepare & reconstitute contents Ergonomic and comfortable to use Robust and sturdy device with optimal size Appropriate as oral vaccine product for paediatric use Programmatic Eliminates the need for cold chain Facilitates easier storage and transportation A much larger UAT would need to be conducted to further validate the findings and assess acceptability and suitability for a novel vaccine delivery device 11

12 HILLEMAN HAS PILOT SCALE MACHINES TO MANUFACTURE THE DUAL CHAMBER DEVICE (VAXIPAK) Output: up to 300 blisters/hour 12

13 HILLEMAN HAS STOPPED FURTHER DEVELOPMENT OF HEAT STABLE ROTAVIRUS VACCINE.. As you all know we have been pursuing development of a novel, heat stable rotavirus vaccine. Hilleman has made the tough decision to stop further development of heat-stable rotavirus vaccine Original Intent Lessons & Timing Market Dynamics Moving Forward Hilleman is keen for global stakeholders to benefit from research and development work and is open for partnership and collaboration opportunities for both Heat-Stabilizing vaccine technology and Dual-Chamber Technology (Vaxipak) 13

14 ACKNOWLEDGEMENTS Dr Zaman: Principal Investigator; icddrb Dr Monica Malone McNeal: Cincinnati Children s Hospital Medical Centre Clinical Unit: Merck Vaccines CRO: PAREXEL International 14

15 Thank you!