Subject(s)
Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/therapy , Antibodies, Monoclonal/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus , Biomedical Research/standards , COVID-19 , Drug Approval , Drug Development , Humans , Immunologic Factors/therapeutic use , Public-Private Sector Partnerships , SARS-CoV-2 , United States , United States Department of Defense , United States Dept. of Health and Human Services , United States Food and Drug AdministrationSubject(s)
Coronavirus Infections/prevention & control , Drug Development , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines , Advisory Committees , Betacoronavirus , COVID-19 , COVID-19 Vaccines , Centers for Disease Control and Prevention, U.S. , Clinical Trials as Topic , Coronavirus Infections/immunology , Drug Approval , Drug Development/methods , Drug Development/organization & administration , Drug Industry , Humans , Immunization/legislation & jurisprudence , Pneumonia, Viral/immunology , RNA, Viral , SARS-CoV-2 , Time Factors , United States , United States Food and Drug Administration , Viral Vaccines/immunologySubject(s)
Drug Industry/economics , Drug Industry/trends , Leadership , Vaccines/economics , Humans , Male , Vaccines/therapeutic useABSTRACT
There is growing recognition that the current research-and-development (R&D) and innovation-regulation ecosystem could be made more efficient to stimulate and support access to innovative therapies for those patients with rare, life-threatening diseases for which there are no adequate licensed therapies. New and progressive thinking on the principles and processes of drug development and regulation are needed in rare disease settings in order to ensure developments are financially sustainable. This paper presents perspectives on the current and emerging schemes for accelerating development of and access to medicines for rare diseases in the European Union.
Subject(s)
Orphan Drug Production , Rare Diseases , European Union , HumansABSTRACT
In two recent clinical trials, a vaccine containing herpes simplex virus (HSV) type 2 glycoprotein D (gD2) and a novel adjuvant AS04 comprising alum (Al) and 3-deactylated monophosphoryl lipid A (3-dMPL) afforded HSV-seronegative women significant protection against HSV-2 genital disease (vaccine efficacy, 73% in study 1 and 74% in study 2) and limited protection against infection (46% in study 1 and 39% in study 2). In the present report, studies in the guinea pig model investigated the protection afforded by gD2/AS04 against HSV-1 and HSV-2 genital herpes and investigated whether immunization could prevent or reduce recurrent disease in guinea pigs that developed mucosal infection. Immunization with gD2/AS04 conveyed nearly complete protection against primary disease with either virus but did not prevent mucosal infection. Guinea pigs immunized with gD2/AS04 were significantly better protected against recurrent disease than were guinea pigs immunized with a gD2/Al vaccine, which suggests that inclusion of 3-dMPL improved protection against latent infection.
Subject(s)
Herpes Genitalis/prevention & control , Herpes Simplex Virus Vaccines/administration & dosage , Herpes Simplex/prevention & control , Herpesvirus 1, Human , Herpesvirus 2, Human , Vaccination , Viral Envelope Proteins/administration & dosage , Animals , Disease Models, Animal , Female , Guinea Pigs , Herpes Genitalis/virology , Herpesvirus 2, Human/immunology , Secondary Prevention , Vaccines, Synthetic/administration & dosage , Viral Envelope Proteins/immunologyABSTRACT
BACKGROUND: An effective prophylactic vaccine would help control the spread of genital herpes. METHODS: We conducted two double-blind, randomized trials of a herpes simplex virus type 2 (HSV-2) glycoprotein-D-subunit vaccine with alum and 3-O-deacylated-monophosphoryl lipid A in subjects whose regular sexual partners had a history of genital herpes. In Study 1, subjects were seronegative for herpes simplex virus type 1 (HSV-1) and HSV-2; in Study 2, subjects were of any HSV serologic status. At months 0, 1, and 6, subjects received either vaccine or a control injection and were evaluated for 19 months. The primary end point was the occurrence of genital herpes disease in all subjects in Study 1 and in HSV-2-seronegative female subjects in Study 2. RESULTS: A total of 847 subjects who were seronegative for both HSV-1 and HSV-2 (268 of them women, in Study 1) and 1867 subjects who were seronegative for HSV-2 (710 of them women, in Study 2) underwent randomization and received injections. Vaccination was well tolerated and elicited humoral and cellular responses. Overall, the efficacy of the vaccine was 38 percent in Study 1 (95 percent confidence interval, -18 to 68 percent; 15 cases occurred in the vaccine group and 24 in the control group), and efficacy in female subjects was 42 percent in Study 2 (95 percent confidence interval, -31 to 74 percent; 9 cases occurred in the vaccine group and 16 in the control group). In both studies, further analysis showed that the vaccine was efficacious in women who were seronegative for both HSV-1 and HSV-2: efficacy in Study 1 was 73 percent (95 percent confidence interval, 19 to 91 percent; P=0.01), and efficacy in Study 2 was 74 percent (95 percent confidence interval, 9 to 93 percent; P=0.02). It was not efficacious in women who were seropositive for HSV-1 and seronegative for HSV-2 at base line or in men. CONCLUSIONS: These studies suggest that the glycoprotein D vaccine has efficacy against genital herpes in women who are seronegative for both HSV-1 and HSV-2 at base line but not in those who are seropositive for HSV-1 and seronegative for HSV-2. It had no efficacy in men, regardless of their HSV serologic status.
