Hoffman S.L.,Sanaria, Inc. |
Vekemans J.,GSK Vaccines |
Richie T.L.,Sanaria, Inc. |
Duffy P.E.,National Institute of Allergy and Infectious Diseases
American Journal of Preventive Medicine | Year: 2015
In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria. © 2015 American Journal of Preventive Medicine and Elsevier Ltd. All rights reserved.
Gomez J.A.,GSK Vaccines Latin America |
Lepetic A.,GSK Vaccines Latin America |
Demarteau N.,GSK Vaccines
BMC Public Health | Year: 2015
Background: In Chile, significant reductions in cervical cancer incidence and mortality have been observed due to implementation of a well-organized screening program. However, it has been suggested that the inclusion of human papillomavirus (HPV) vaccination for young adolescent women may be the best prospect to further reduce the burden of cervical cancer. This cost-effectiveness study comparing two available HPV vaccines in Chile was performed to support decision making on the implementation of universal HPV vaccination. Methods: The present analysis used an existing static Markov model to assess the effect of screening and vaccination. This analysis includes the epidemiology of low-risk HPV types allowing for the comparison between the two vaccines (HPV-16/18 AS04-adjuvanted vaccine and the HPV-6/11/16/18 vaccine), latest cross-protection data on HPV vaccines, treatment costs for cervical cancer, vaccine costs and 6% discounting per the health economic guideline for Chile. Results: Projected incremental cost-utility ratio (ICUR) and incremental cost-effectiveness ratio (ICERs) for the HPV-16/18 AS04-adjuvanted vaccine was 116 United States (US) dollars per quality-adjusted life years (QALY) gained or 147 US dollars per life-years (LY) saved, while the projected ICUR/ICER for the HPV-6/11/16/18 vaccine was 541 US dollars per QALY gained or 726 US dollars per LY saved. Introduction of any HPV vaccine to the present cervical cancer prevention program of Chile is estimated to be highly cost-effective (below 1X gross domestic product [GDP] per capita, 14278 US dollars). In Chile, the addition of HPV-16/18 AS04-adjuvanted vaccine to the existing screening program dominated the addition of HPV-6/11/16/18 vaccine. In the probabilistic sensitivity analysis results show that the HPV-16/18 AS04-adjuvanted vaccine is expected to be dominant and cost-saving in 69.3% and 77.6% of the replicates respectively. Conclusions: The findings indicate that the addition of any HPV vaccine to the current cervical screening program of Chile will be advantageous. However, this cost-effectiveness model shows that the HPV-16/18 AS04-adjuvanted vaccine dominated the HPV-6/11/16/18 vaccine. Beyond the context of Chile, the data from this modelling exercise may support healthcare policy and decision-making pertaining to introduction of HPV vaccination in similar resource settings in the region. © 2014 Gomez et al.; licensee BioMed Central Ltd.
Barocchi M.A.,GSK Vaccines |
Black S.,Cincinnati Childrens Hospital |
Rappuoli R.,GSK Vaccines
Science Translational Medicine | Year: 2016
Vaccines have the potential to transform the health of all individuals and to reduce the health inequality between rich and poor countries. However, to achieve these goals, it is no longer sufficient to prioritize vaccine development using cost-effectiveness as the sole indicator. During a symposium entitled "Mission Grand Convergence - The Role of Vaccines," held in Siena, Italy, in July 2015, key stakeholders agreed that the prioritization of vaccine development and deployment must use multicriteria decision-making based on the following core concepts: (i) mortality and severity of the disease, (ii) vaccine safety considerations, and (iii) economic evaluation that captures the full benefits of vaccination. © 2016, American Association for the Advancement of Science. All rights reserved.
Ulmer J.B.,GSK Vaccines |
Geall A.J.,Avidity Nanomedicines, Llc
Current Opinion in Immunology | Year: 2016
Nucleic acid-based vaccines are being developed as a means to combine the positive attributes of both live-attenuated and subunit vaccines. Viral vectors and plasmid DNA vaccines have been extensively evaluated in human clinical trials and have been shown to be safe and immunogenic, although none have yet been licensed for human use. Recently, mRNA based vaccines have emerged as an alternative approach. They promise the flexibility of plasmid DNA vaccines, without the need for electroporation, but with enhanced immunogenicity and safety. In addition, they avoid the limitations of anti-vector immunity seen with viral vectors, and can be dosed repeatedly. This review highlights the key papers published over the past few years and summarizes prospects for the near future. © 2016
Medini D.,GSK Vaccines |
Stella M.,GSK Vaccines |
Wassil J.,GSK Vaccines
Vaccine | Year: 2015
Recently approved in the EU, US, Australia, and Canada, 4CMenB (Bexsero®, GSK Vaccines) is a multi-component meningococcal B (MenB) vaccine containing 3 surface exposed recombinant proteins (fHbp, NadA, and NHBA) and New Zealand strain outer membrane vesicles (NZ OMV) containing PorA 1.4. The accepted correlate of protection to assess response to MenB vaccines, the serum bactericidal assay with human complement, is impractical for large panels of strains with diverse antigenic profile and expression. Therefore, the Meningococcal Antigen Typing System (MATS) was developed to identify MenB strains with a high likelihood of being covered by 4CMenB. MATS is used to assess MenB strain coverage without requiring sera, an advantage for testing large panels of bacterial isolates. MATS provides an accurate, conservative estimate of 4CMenB coverage. In a public-private partnership, 10 reference laboratories around the world were established and standardized to facilitate the timely collection and analysis of regional data. MATS has global public health implications for informing local policy makers of the predicted effect of the implementation of the 4CMenB vaccine. Coverage estimates are similar to or better than other recently approved vaccines, ranging from 66% to 91%. The use of MATS in post-vaccine implementation surveillance could provide data regarding vaccine effectiveness in the field and duration of protection on a global scale that will aid in the development of vaccine booster schedules, if necessary. This MATS approach could potentially be applied rapidly to assess epidemiology of other bacterial pathogens and coverage by other protein-based vaccines. © 2015 The Authors.
Lal H.,Global Clinical Research and Development |
Cunningham A.L.,Westmead Millennium Institute for Medical Research |
Cunningham A.L.,University of Sydney |
Godeaux O.,GSK Vaccines |
And 12 more authors.
New England Journal of Medicine | Year: 2015
Background: In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01Badjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response. Methods: We conducted a randomized, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults. Results: A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups. Conclusions: The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
Kaslow D.C.,PATH |
Biernaux S.,GSK Vaccines
Vaccine | Year: 2015
The Malaria Vaccine Technology Roadmap calls for a 2015 landmark goal of a first-generation malaria vaccine that has protective efficacy against severe disease and death, lasting longer than one year. This review focuses on product development efforts over the last five years of RTS, S, a pre-erythrocytic, recombinant subunit, adjuvanted, candidate malaria vaccine designed with this goal of a first-generation malaria vaccine in mind. RTS, S recently completed a successful pivotal Phase III safety, efficacy and immunogenicity study. Although vaccine efficacy was found to be modest, a substantial number of cases of clinical malaria were averted over a 3-4 years period, particularly in settings of significant disease burden. European regulators have subsequently adopted a positive opinion under the Article 58 procedure for an indication of active immunization of children aged 6 weeks up to 17 months against malaria caused by Plasmodium falciparum and against hepatitis B. Further evaluations of the benefit, risk, feasibility and cost-effectiveness of RTS, S are now anticipated through policy and financing reviews at the global and national levels. © 2015.
Kreimer A.R.,U.S. National Institutes of Health |
Struyf F.,GSK Vaccines |
Del Rosario-Raymundo M.R.,San Pablo Colleges Medical Center |
Hildesheim A.,U.S. National Institutes of Health |
And 8 more authors.
The Lancet Oncology | Year: 2015
Background: There is some evidence to suggest that one or two doses of the HPV vaccine provides similar protection to the three-dose regimen. The main aim of the study was to ascertain HPV-16/18 vaccine efficacy in both full and naive cohorts and to explore protection conferred against non-vaccine HPV types, by number of doses received. Methods: Summary data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and ~the PATRICIA trial (. NCT001226810), two phase 3, double-blind, randomised controlled clinical trials of the HPV-16/18 AS04-adjuvanted vaccine in young women, were combined in a post-hoc analysis (GlaxoSmithKline [GSK] e-track number 202142) to investigate the efficacy of fewer than three doses of the HPV-16/18 vaccine after 4 years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet, some received fewer doses. After exclusion of women with less than 12 months of follow-up or those who were HPV-16/18 DNA-positive at enrolment (for the HPV-16/18 endpoint), we calculated vaccine efficacy against one-time detection of incident HPV infections after three, two, and one dose(s). The primary study endpoint was one-time detection of first incident HPV-16/18 infections accumulated during the follow-up phase. Findings: We assessed vaccine efficacy against incident HPV-16/18 infection in the modified total vaccinated cohort (22 327 received three doses, 1185 two doses, 543 one dose). Vaccine efficacy against incident HPV-16/18 infections for three doses was 77·0% (95% CI 74·7-79·1), two doses was 76·0% (62·0-85·3), and one dose was 85·7% (70·7-93·7). Vaccine efficacy against incident HPV-31/33/45 infections for three doses was 59·7% (56·0-63·0), two doses was 37·7% (12·4-55·9), and one dose was 36·6% (-5·4 to 62·2). Vaccine efficacy against incident HPV-16/18 infection for two-dose women who received their second dose at 1 month was 75·3% (54·2-87·5) and 82·6% (42·3-96·1) for those who received the second dose at 6 months (CVT data only). Vaccine efficacy against HPV-31/33/45 for two-dose women who received their second dose at 6 months (68·1%, 27·0-87·0; CVT data only), but not those receiving it at one month (10·1%, -42·0 to 43·3), was similar to the three-dose group. Interpretation: 4 years after vaccination of women aged 15-25 years, one and two doses of the HPV-16/18 vaccine seem to protect against cervical HPV-16/18 infections, similar to the protection provided by the three-dose schedule. Two doses separated by 6 months additionally provided some cross-protection. These data argue for a direct assessment of one-dose efficacy of the HPV-16/18 vaccine. Funding: US National Cancer Institute, National Institutes of Health Office of Research on Women's Health, and Ministry of Health of Costa Rica (CVT); GlaxoSmithKline Biologicals SA (PATRICIA). © 2015 Elsevier Ltd.
News Article | November 14, 2016
Led by former senior FDA official Casper Uldriks, ComplianceOnline’s on-demand seminar on FDA recalls returns to California in 2017. The two-day training program will address recall regulations, recall classification, and FDA’s recall database. This seminar will help you understand FDA's recall policy, how to establish a roadmap for conducting recalls and manage possible FDA enforcement actions. Attendees will take away practical knowledge on how to work with FDA staff during a recall, and how you can prepare for inspectional follow up. This in-person training will assist recall managers, quality assurance managers, regulatory affairs directors, and risk and product liability managers, manufacturers’ sales and marketing managers, own label distributors and others within an organization. The 2016 ComplianceOnline food recall seminar participation from various healthcare and pharma organizations, such as Philips Healthcare, Mevion Medical Systems, Inc., Abbott Vascular, Edwards Lifesciences, Takeda Pharmaceutical Company Ltd, GSK Vaccines and others, have made the event an industry platform to reckon with. Seminar instructor Casper Uldriks brings over 32 years of experience from the FDA. He specialized in the FDA’s medical device program as a field investigator, served as a senior manager in the Office of Compliance and an Associate Center Director for CDRH. He developed enforcement actions and participated in the implementation of new statutory requirements. Based on his exceptionally broad experience and knowledge, he can synthesize FDA’s domestic and international operational programs, institutional policy and thicket of legal variables into a coherent picture. For more information or to register for the seminar, please click here. Dates: Thursday, February 9, 2017 (8.30 AM- 4.30 PM) and Friday, February 10, 2017 (8.30 AM- 4.30 PM) Location: San Jose, CA Registration Cost: $1,899.00 per registration Early bird discounts: For discounts on early registrations, please click here. Register by phone: Please call our customer service specialists at +1-888-717-2436 or email to customercare(at)complianceonline.com For more information on ComplianceOnline or to browse through our trainings, please visit our website. ComplianceOnline is a leading provider of regulatory compliance trainings for companies and professionals in regulated industries. ComplianceOnline has successfully trained over 35,000 professionals from 9,000 companies to comply with the requirements of regulatory agencies. ComplianceOnline is headquartered in Palo Alto, California and can be reached at http://www.complianceonline.com. ComplianceOnline is a MetricStream portal. MetricStream (http://www.metricstream.com) is a market leader in Enterprise-wide Governance, Risk, Compliance (GRC) and Quality Management Solutions for global corporations. For more information please contact:
News Article | October 29, 2016
Preliminary data from the world’s first national meningitis B immunisation programme with Bexsero1, launched one year ago in the UK, shows the estimated effectiveness of the vaccine at 83 percent against any meningitis B strain and 94 percent against vaccine preventable strains, for all children receiving the first two of three recommended doses 2. Reported cases of the disease have dropped 50 percent in the vaccine-eligible population in the first ten months of the programme, compared to the average number of cases over the last four years. These data were presented today by Public Health England (PHE) at the International Pathogenic Neisseria Conference (IPNC) in Manchester, UK. Uptake of the vaccine in the UK national immunisation programme is high. In more than 600,000 infants aged 0-1 year old, eligible for the vaccine, more than 90 percent received two doses. Dr. Thomas Breuer, Chief Medical Officer, GSK Vaccines commented: “We are extremely encouraged by the initial results of the UK programme, which demonstrate that Bexsero helps to protect babies in the UK from this often life-threatening disease. The data substantially advance our understanding of the impact of meningitis B vaccines in a real world setting and may help inform public health authorities around the world about their future use. The report shared provides reassurance to parents who have already vaccinated their children or wish to help protect their children from meningitis B in the future.” Invasive meningococcal B disease is the leading cause of life-threatening meningitis in the industrialised world. Although not common, invasive meningococcal B disease develops rapidly, typically amongst previously healthy children and adolescents, and results in high morbidity and mortality. Initial symptoms can often resemble flu, making it difficult to diagnose. About one in 10 of those who contract the disease will die, even with appropriate treatment. Additionally, up to 20 percent of those who survive bacterial meningitis may suffer a major physical or neurological disability (limb loss, hearing loss or seizures).3,4 Bexsaro is currently the only meningococcal B vaccine licenced in Europe. The UK national immunization programme is the first such programme for the prevention of menigitis B in the world. Bexsaro is currently the only meningococcal B vaccine licenced in Europe. The UK national immunization programme is the first such programme for the prevention of menigitis B in the world. Bexsaro is currently the only meningococcal B vaccine licenced in Europe. The UK national immunization programme is the first such programme for the prevention of menigitis B in the world.Bexsero is currently the only meningococcal B vaccine licensed in Europe. The UK national immunisation programme is the first such programme for the prevention of meningitis B in the world. Infants are immunised at two and four months of age, with a booster dose at 12 months, outside of the licensed dosing schedule*, but in line with recommendations issued by the UK advisory body on immunisation2. The data presented today demonstrate the immediate impact on meningococcal B disease rates in the eligible population following two doses of the vaccine. More data are expected as the first infants from the programme receive their booster dose later this year. Linda Glennie, head of research at the Meningitis Research Foundation said, “It is great to see this early evidence that the national meningitis B immunisation programme for children under age one is effective. We hope that other countries burdened by meningitis B will now consider protecting their people from this deadly disease. Meningitis and septicaemia can kill in hours, and leave a substantial number of survivors with life-changing after-effects. We will continue to gather evidence that will unlock expertise about meningitis B vaccination.” Incidence of meningitis B is highest in infants under one year old and the ultimate goal of meningococcal vaccination is to reduce the total burden of disease. The data presented today at IPNC shows this is now happening in the UK. GSK looks forward to further analyses from PHE on the vaccine’s effectiveness over the coming months and years. Bexsero is licensed in more than 35 countries5, including the U.S. These countries include the member states of the European Union and European Economic Area, Australia, Argentina, Chile and Uruguay, where Bexsero is approved for individuals two months of age and older, and in Canada for those aged 2 months to 17 years of age. In the U.S., Bexsero is approved for use in individuals from 10 years through 25 years of age. In Brazil, Bexsero is approved for use in individuals from two months to 50 years of age. Refer to SPC for adverse events and safety guidance. GSK – one of the world’s leading research-based pharmaceutical and healthcare companies. For further information please visit www.gsk.com. Cautionary statement regarding forward-looking statements GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Risk factors' in the company's Annual Report on Form 20-F for 2015. 2 In line with the recommendations made by the Joint Committee on Vaccination and Immunisation, (JCVI). JCVI position statement on use of Bexsero® meningococcal B vaccine in the UK. March 2014. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/294245/JCVI_Statement_on_MenB.pdf 5 Watson PS, Turner DPJ. Clinical experience with the meningococcal B vaccine, Bexsero®: Prospects for reducing the burden of meningococcal serogroup B disease. Vaccine 34 (2016) 875–880 http://dx.doi.org/10.1016/j.vaccine.2015.11.057