Viiv Healthcare Company

THE PURPOSE OF THIS SUBCONTRACT IS TO ENTER INTO AN IDIQ FOR THE SUPPLY OF MEDICINE FOR HIV FOR USE IN MULTIPLE COUNTRIES SUPPORTED BY THE GHSC-PSM PROJECT.

STREP A IS A GRAM-POSITIVE BACTERIUM WITH A RICH REPERTOIRE OF VIRULENCE FACTORS THAT ALLOWS FOR A WIDE SPECTRUM OF CLINICAL MANIFESTATIONS. STREP A IS THE COMMON CAUSE OF BACTERIAL SORE THROATS (PHARYNGITIS) AND SKIN INFECTIONS (IMPETIGO) BUT THE RANGE OF DISEASES CAUSED BY THIS PATHOGEN EXTENDS FROM THESE COMMON SUPERFICIAL INFECTIONS TO MORE COMPLICATED CLINICAL OUTCOMES SUCH AS INVASIVE DISEASES (E.G., CELLULITIS AND SEPSIS), TOXIN-MEDIATED DISEASES (E.G., SCARLET FEVER, TOXIC SHOCK SYNDROME AND NECROTIZING FASCIITIS) AND AUTOIMMUNE SEQUELAE (E.G., ACUTE RHEUMATIC FEVER, ARF; RHEUMATIC HEART DISEASE, RHD; AND POST-STREPTOCOCCAL GLOMERULONEPHRITIS, PSGN). ACCORDING TO THE WHO, STREP A ACCOUNTS FOR MORE THAN 0.5 MILLION DEATHS EACH YEAR, A SIMILAR DEATH TOLL TO MALARIA. MOST DEATHS ARE CAUSED BY RHD, AN AUTOIMMUNE SYNDROME CAUSED BY REPEATED UNDERTREATED SUPERFICIAL STREP A INFECTIONS (E.G., PHARYNGITIS AND IMPETIGO), AND MOST OF THIS BURDEN LIES IN IMPOVERISHED COMMUNITIES WHERE POOR SANITIZATION, OVERCROWDING, MALNUTRITION AND LACK OF ACCESS TO HEALTHCARE PREVAIL. STREP A IS STRICTLY A HUMAN PATHOGEN AND COMMUNITIES IN SETTINGS OF EXTREME POVERTY ARE EASY TARGETS FOR THIS HIGHLY INFECTIOUS MICROORGANISM. PHARYNGITIS (>616 MILLION CASES PER YEAR) AND IMPETIGO (>162 MILLION CASES PER YEAR) ARE RESPONSIBLE FOR THE GREATEST ABSOLUTE NUMBER OF STREP A CLINICAL MANIFESTATIONS. THEY ARE NOT ONLY RESPONSIBLE FOR THE DEVELOPMENT OF AUTOIMMUNE SEQUELAE (ARF AND RHD) BUT ALSO FOR ANTIBIOTIC TREATMENTS THAT ARE FREQUENTLY INCONSISTENT WITH GUIDELINES: I) BROAD-SPECTRUM ANTIBIOTICS ARE OFTEN USED UNNECESSARILY, II) OVER-THE-COUNTER OVERUSE IN DEVELOPING COUNTRIES, III) INAPPROPRIATE PRESCRIPTIONS OF ANTIBIOTICS (>1/3) FOR SORE THROATS DUE TO VIRAL INFECTIONS. SORE THROATS AND IMPETIGO ARE TYPICALLY TREATED WITH 5-10 GRAMS OF AMPICILLIN PER REGIMEN THAT, TOGETHER, COULD ACCOUNT FOR >4 THOUSAND TONS OF ANTIBIOTICS USED IN THE APPROPRIATE AND INAPPROPRIATE TREATMENT OF STREP A INFECTIONS PER YEAR, WHICH CONTRIBUTE TO THE LONG-TERM DYSBIOSIS OF COMMENSAL FLORA AND EMERGENCE OF ANTIBIOTIC RESISTANCE. THEREFORE, THE PREVENTION OF STREP A SUPERFICIAL INFECTIONS BY A VACCINE WOULD NOT ONLY PREVENT THE BURDEN ASSOCIATED WITH PHARYNGITIS AND IMPETIGO BUT ALSO ASSOCIATED ANTIBIOTIC PRESCRIPTIONS AND THE AUTOIMMUNE CONSEQUENCES OF THESE INFECTIONS. GSK STREP A VACCINE AIMS TO REDUCE AND PREVENT THE INCIDENCE AND SEVERITY OF STREP A SUPERFICIAL INFECTIONS (E.G., PHARYNGITIS AND IMPETIGO) AND CONSEQUENTLY REDUCE THE GLOBAL BURDEN OF ASSOCIATED AUTOIMMUNE SEQUELAE (ARF AND RHD) AND ASSOCIATED ANTIBIOTIC PRESCRIPTIONS, WHICH ARE THE BASIS FOR THE INCREASED ANTIBIOTIC RESISTANCE OF THIS PATHOGEN AND BYSTANDER SELECTIVE PRESSURE ON THE HUMAN MICROBIOME. IN THE CARB-X OPTION STAGE, GSK WILL PERFORM A PHASE 1 DOSE-ESCALATION STUDY IN HEALTHY ADULTS WITH A SAFETY AND IMMUNOGENICITY OUTCOME. OUR LONG-TERM VISION AND KEY STRATEGIC GOALS ARE TIGHTLY ALIGNED WITH THE WHO, AS DESCRIBED IN ITS PREFERRED PRODUCT CHARACTERISTICS (PPC) AND TECHNOLOGY ROADMAP FOR A STREP A VACCINE: “A SAFE, GLOBALLY EFFECTIVE AND AFFORDABLE STREP A VACCINE IS NEEDED TO PREVENT AND POTENTIALLY ELIMINATE ACUTE STREP A INFECTIONS (PHARYNGITIS, SKIN INFECTIONS, CELLULITIS, INVASIVE DISEASE) AND ASSOCIATED ANTIBIOTIC USE, IMMUNE-MEDIATED SEQUELAE (KIDNEY DISEASE, ARF AND RHD) AND ASSOCIATED MORTALITY”. ALTHOUGH LOW- AND MIDDLE-INCOME COUNTRIES WOULD MAINLY BENEFIT FROM STREP A VACCINES, CONSIDERING THAT AN ESTIMATED 82% OF THE RHD DEATHS OCCURS IN REGIONS WITH AN ENDEMIC DISEASE PATTERN, AN EFFECTIVE VACCINE WOULD HAVE GLOBAL IMPLICATIONS.