72 research outputs found
Registering New Drugs for Low-Income Countries: The African Challenge
Mary Moran and colleagues discuss the best strategies for African regulators to
be supported in their efforts to evaluate and approve drugs for their own
populations
The drug and vaccine landscape for neglected diseases (2000–11): a systematic assessment
Background In 1975–99, only 1·1% of new therapeutic products had been developed for neglected diseases. Since
then, several public and private initiatives have attempted to mitigate this imbalance. We analysed the research and
development pipeline of drugs and vaccines for neglected diseases from 2000 to 2011.
Methods We searched databases of drug regulatory authorities, WHO, and clinical trial registries for entries made
between Jan 1, 2000, and Dec 31, 2011. We defi ned neglected diseases as malaria, tuberculosis, diarrhoeal diseases,
neglected tropical diseases (NTDs; WHO defi nition), and other diseases of poverty according to common defi nitions.
Findings Of the 850 new therapeutic products registered in 2000–11, 37 (4%) were indicated for neglected diseases,
comprising 25 products with a new indication or formulation and eight vaccines or biological products. Only four
new chemical entities were approved for neglected diseases (three for malaria, one for diarrhoeal disease), accounting
for 1% of the 336 new chemical entities approved during the study period. Of 148 445 clinical trials registered in
Dec 31, 2011, only 2016 (1%) were for neglected diseases.
Interpretation Our fi ndings show a persistent insuffi ciency in drug and vaccine development for neglected diseases.
Nevertheless, these and other data show a slight improvement during the past 12 years in new therapeutics development
and registration. However, for many neglected diseases, new therapeutic products urgently need to be developed and
delivered to improve control and potentially achieve elimination
Implications of asymptomatic infection for the natural history of selected parasitic tropical diseases
Progress has been made in the control or elimination of
tropical diseases, with a significant reduction of incidence.
However, there is a risk of re-emergence if the factors fueling
transmission are not dealt with. Although it is essential to
understand these underlying factors for each disease,
asymptomatic carriers are a common element that may promote
resurgence; their impact in terms of proportion in the
population and role in transmission needs to be determined. In
this paper, we review the current evidence on whether or not to
treat asymptomatic carriers given the relevance of their role in
the transmission of a specific disease, the efficacy and
toxicity of existing drugs, the Public Health interest, and the
benefit at an individual level, for example, in Chagas disease,
to prevent irreversible organ damage. In the absence of other
control tools such as vaccines, there is a need for safer drugs
with good risk/benefit profiles in order to change the paradigm
so that it addresses the complete infectious process beyond
manifest disease to include treatment of non-symptomatic
infected persons
New regimens of benznidazole monotherapy and in combination with fosravuconazole for treatment of Chagas disease (BENDITA): a phase 2, double-blind, randomised trial
Background: Current treatment for Chagas disease with the only available drugs, benznidazole or nifurtimox, has substantial limitations, including long treatment duration and safety and tolerability concerns. We aimed to evaluate the efficacy and safety of new benznidazole monotherapy regimens and combinations with fosravuconazole, in the treatment of Chagas disease. Methods: We did a double-blind, double-dummy, phase 2, multicentre, randomised trial in three outpatient units in Bolivia. Adults aged 18–50 years with chronic indeterminate Chagas disease, confirmed by serological testing and positive qualitative PCR results, were randomly assigned (1:1:1:1:1:1:1) to one of seven treatment groups using a balanced block randomisation scheme with an interactive response system. Participants were assigned to benznidazole 300 mg daily for 8 weeks, 4 weeks, or 2 weeks, benznidazole 150 mg daily for 4 weeks, benznidazole 150 mg daily for 4 weeks plus fosravuconazole, benznidazole 300 mg once per week for 8 weeks plus fosravuconazole, or placebo, with a 12-month follow-up period. The primary endpoints were sustained parasitological clearance at 6 months, defined as persistent negative qualitative PCR results from end of treatment, and incidence and severity of treatment-emergent adverse events, serious adverse events, and adverse events leading to treatment discontinuation. Primary efficacy analysis was based on the intention-to-treat and per-protocol populations and secondary efficacy analyses on the per-protocol population. Safety analyses were based on the as-treated population. Recruitment is now closed. This trial is registered with ClinicalTrials.gov, NCT03378661. Findings: Between Nov 30, 2016, and July 27, 2017, we screened 518 patients, and 210 were enrolled and randomised. 30 patients (14%) were assigned to each treatment group. All 210 randomised patients were included in the intention-to-treat population, and 190 (90%) were included in the per-protocol population. In the intention-to-treat analysis, only one (3%) of 30 patients in the placebo group had sustained parasitological clearance at 6 months of follow-up. Sustained parasitological clearance at 6 months was observed in 25 (89%) of 28 patients receiving benznidazole 300 mg daily for 8 weeks (rate difference vs placebo 86% [95% CI 73–99]), 25 (89%) of 28 receiving benznidazole 300 mg daily for 4 weeks (86% [73–99]), 24 (83%) of 29 receiving benznidazole 300 mg daily for 2 weeks (79% [64–95]), 25 (83%) of 30 receiving benznidazole 150 mg daily for 4 weeks (80% [65–95]), 23 (85%) of 28 receiving benznidazole 150 mg daily for 4 weeks plus fosravuconazole (82% [67–97]), and 24 (83%) of 29 receiving benznidazole 300 mg weekly for 8 weeks plus fosravuconazole (79% [64–95]; p<0·0001 for all group comparisons with placebo). Six patients (3%) had ten serious adverse events (leukopenia [n=3], neutropenia [n=2], pyrexia, maculopapular rash, acute cholecystitis, biliary polyp, and breast cancer), eight had 12 severe adverse events (defined as interfering substantially with the patient's usual functions; elevated alanine aminotransferase [n=4], elevated gamma-glutamyltransferase [n=2], elevated aspartate aminotransferase [n=1], neutropenia [n=3], leukopenia [n=1], and breast cancer [n=1]), and 15 (7%) had adverse events that led to treatment discontinuation (most of these were in the groups who received benznidazole 300 mg daily for 8 weeks, benznidazole 300 mg once per week for 8 weeks plus fosravuconazole, and benznidazole 150 mg daily for 4 weeks plus fosravuconazole). No adverse events leading to treatment discontinuation were observed in patients treated with benznidazole 300 mg daily for 2 weeks or placebo. There were no treatment-related deaths. Interpretation: Benznidazole induced effective antiparasitic response, regardless of treatment duration, dose, or combination with fosravuconazole, and was well tolerated in adult patients with chronic Chagas disease. Shorter or reduced regimens of benznidazole could substantially improve treatment tolerability and accessibility, but further studies are needed to confirm these results. Funding: Drugs for Neglected Diseases initiative (DNDi). Translation: For the Spanish translation of the abstract see Supplementary Materials section.Fil: Torrico, Faustino. Fundación Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio Ambiente; Bolivia. Universidad Mayor de San Simón; BoliviaFil: Gascón, Joaquim. Instituto de Salud Global de Barcelona; España. Universidad de Barcelona; EspañaFil: Barreira, Fabiana. DNDi Latin America; BrasilFil: Blum, Bethania. DNDi Latin America; BrasilFil: Almeida, Igor C. University of Texas at El Paso; Estados UnidosFil: Alonso Vega, Cristina. DNDi Latin America; Brasil. Instituto de Salud Global de Barcelona; EspañaFil: Barboza, Tayná. DNDi Latin America; BrasilFil: Bilbe, Graeme. Drugs For Neglected Diseases Initiative; SuizaFil: Correia, Erika. DNDi Latin America; BrasilFil: Garcia, Wilson. Universidad Mayor de San Simón; Bolivia. Fundación Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio Ambiente ; BoliviaFil: Ortiz, Lourdes. Universidad Autónoma Juan Misael Saracho; Bolivia. Fundación Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio Ambiente; BoliviaFil: Parrado, Rudy. Universidad Mayor de San Simón; BoliviaFil: Ramirez Gomez, Juan Carlos. Consejo Nacional de Investigaciones CientÃficas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de ParasitologÃa "Dr. Mario Fatala Chaben"; ArgentinaFil: Ribeiro, Isabela. Drugs For Neglected Diseases Initiative; SuizaFil: Strub Wourgaft, Nathalie. Drugs For Neglected Diseases Initiative; SuizaFil: Vaillant, Michel. Luxembourg Institute Of Health; LuxemburgoFil: Sosa-Estani, Sergio Alejandro. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en EpidemiologÃa y Salud Pública. Instituto de Efectividad ClÃnica y Sanitaria. Centro de Investigaciones en EpidemiologÃa y Salud Pública; Argentina. DNDi Latin America; Brasi
Beyond the jab: A need for global coordination of pharmacovigilance for COVID-19 vaccine deployment Comment
Commentary - No abstract available
Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model
The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world’s population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, especially those at low cost and which are immediately available to patients, particularly in low- and middle-income countries. Prior in vitro and observational studies have shown that fluoxetine, possibly through its inhibitory effect on the acid sphingomyelinase/ceramide system, could be a promising antiviral and anti-inflammatory treatment against COVID-19. In this report, we evaluated the potential antiviral and anti-inflammatory activities of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and against variants of concern in vitro, i.e., SARS-CoV-2 ancestral strain, Alpha B.1.1.7, Gamma P1, Delta B1.617 and Omicron BA.5. Fluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres and expression of several inflammatory markers (i.e., IL-6, TNFα, CCL2 and CXCL10). It also inhibited the replication of all variants of concern in vitro. A modulation of the ceramide system in the lung tissues, as reflected by the increase in the ratio HexCer 16:0/Cer 16:0 in fluoxetine-treated mice, may contribute to explain these effects. Our findings demonstrate the antiviral and anti-inflammatory properties of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and its in vitro antiviral activity against variants of concern, establishing fluoxetine as a very promising candidate for the prevention and treatment of SARS-CoV-2 infection and disease pathogenesis
Correcting COVID-19 vaccine misinformation: Lancet Commission on COVID-19 Vaccines and Therapeutics Task Force Members.
Commentary - No abstract available
Operation Warp Speed: implications for global vaccine security
Several global efforts are underway to develop COVID-19 vaccines, and interim analyses from phase 3 clinical testing have been announced by nine organisations: Pfizer, the Gamaleya Research Institute of Epidemiology and Microbiology, Moderna, AstraZeneca, Sinopharm Group, Sinovac Biotech, Johnson & Johnson, Novavax, and CanSino Biologics. The US programme known as Operation Warp Speed provided US$18 billion in funding for development of vaccines that were intended for US populations. Depending on safety and efficacy, vaccines can become available through mechanisms for emergency use, expanded access with informed consent, or full licensure. An important question is: how will these Operation Warp Speed vaccines be used for COVID-19 prevention in global health settings? We address some key questions that arise in the transition from US to global vaccine prevention efforts and from ethical and logistical issues to those that are relevant to global vaccine security, justice, equity, and diplomacy
Urgent needs to accelerate the race for COVID-19 therapeutics.
No abstract available
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