Tecovirimat for Monkeypox in Central African Republic under Expanded Access

Mbrenga, Festus; Nakouné, Emmanuel; Malaka, Christian; Bourner, Josephine; Dunning, Jake; Vernet, Guy; Horby, Peter; Olliaro, Piero

doi:10.1056/nejmc2210015

Cited by 21 publications

(21 citation statements)

References 3 publications

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“…Our previous, uncontrolled, descriptive data on treated mpox patients showed a progressive decline in MPXV viral load in the course of antiviral treatment [10] ; nevertheless, in other cohorts [23-24] of untreated patients, viral shedding also occurred mainly during the first two weeks of the disease after which it naturally declined. In our present analysis, there was no evidence for a difference in viral load reduction after an average of 12 days from the date of symptoms onset when comparing treated versus untreated mpox patients after controlling for potential immortal and confounding bias.…”

Section: Discussionmentioning

confidence: 95%

“…Tecovirimat (TPOXX) was authorized in USA [4] and EU [5] for use against mpox based on promising results from initial studies in animals [6] and evidence of safety in healthy human volunteers [7] ; TPOXX is also the first choice treatment for mpox suggested by CDC [3] . In recent series, oral TPOXX was reported as safe and well tolerated [8][9][10][11][12][13] , no worsening was observed in treated patients, and subjective improvement was reported after a median time of 3 days after treatment. However, the lack of a control group made it difficult to assess treatment effectiveness, and the limited supply did not allow the early use of TPOXX.…”

Section: Introductionmentioning

confidence: 99%

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Poor evidence for an effect of tecovirimat in shortening recovery time in hospitalized mpox cases from real-world data

Mazzotta¹,

Lepri²,

Lanini³

et al. 2023

Preprint

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Objectives To assess the effectiveness of tecovirimat (TPOXX) for treating mpox in terms of difference in healing time and extent of viral clearance. Design Emulation of a target trial based on observational data. Setting Italy Participants Forty-one men hospitalized for mpox as of September 29th, 2022. Main outcome measures Main outcome was the time to clinical recovery. Secondary outcome was the variation in viral load in the upper respiratory tract (URT) after treatment. Results The median time from symptoms onset to hospital admission and to initiation of TPOXX was 4 days (IQR 2-6) and 10 days (IQR 8-11), respectively. Fifteen patients completed a course of therapy. No deaths were observed; the overall median healing time was 21 days (IQR 17-26). We found no evidence for a significant improvement in recovery time in treated vs. untreated patients, with an estimated mean of 14.7 days for both groups. A subset of 13 patients had URT samples at T1 (median of 5 days (IQR 3-7) from symptoms onset) and T2 (median 7 days (IQR 7-9) from T1). Overall, mean viral load was 4.65 (0.30) vs. 4.91 (0.35) (log2 scale of cycle threshold) at T1 and T2, respectively. In the unadjusted analysis, variation over T1-T2 was lower in the treated 0.13 log2 (SD=0.53) vs. untreated 0.37 (0.50), although not statistically significant (unpaired t-test p=0.41). After controlling for confounding, there was no evidence for a difference in the potential changes over T1-T2 by treatment arm, and our estimate of the average treatment effect (ATE) was consistent with no difference by treatment group, although with large 95% CI around these estimates. Conclusions Our analysis seems to exclude a clinically important effect of TPOXX in hospitalized mpox patients when compared to no treatment. These data are one of the valuable currently available sources of evidence to guide treatment decisions in patients hospitalized with TPOXX. Pending more robust data from randomized comparisons, the use of TPOXX should be restricted to the clinical trials setting.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Poor evidence for an effect of tecovirimat in shortening recovery time in hospitalized mpox cases from real-world data

Mazzotta¹,

Lepri²,

Lanini³

et al. 2023

Preprint

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“…Ongoing clinical trials for investigational use of oral tecovirimax include those among adults and children weighing at least 2.5–3 kg in the DRC and USA [36–38], and among adolescents and adults 14 years and older in Brazil [39]. Findings from a small study of 14 PCR-confirmed mpox patients aged 4–38 years in the Central African Republic suggest that tecovirimax is well tolerated [40], however, given that there were no controls, it is difficult to determine drug efficacy in this study. Due to prior experience with smallpox, other potential mpox treatments under investigation include the antiviral cidofovir, its derivative brincidofovir, and vaccinia (cowpox) immune globulin, but data on efficacy in mpox is still limited [35 ▪ ].…”

Section: Main Narrativementioning

confidence: 99%

A global update of mpox (monkeypox) in children

Sam-Agudu

Martyn‐Dickens

Ewa

2023

Current Opinion in Pediatrics

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Purpose of reviewHuman mpox disease (formerly monkeypox) was first diagnosed in an infant in the Democratic Republic of the Congo in 1970. Mpox was rarely reported outside West and Central Africa until the global outbreak in May 2022. On 23 July 2022, the WHO declared mpox a public health emergency of international concern. These developments warrant a global update on pediatric mpox.Recent findingsMpox epidemiology in endemic African countries has changed from predominantly affecting children under 10 years to adults 20–40 years old. This shift also applies to the global outbreak, where 18–44-year-old adult men who have sex with men are disproportionately affected. Furthermore, the proportion of children affected in the global outbreak is less than 2%, while children under 18 years constitute nearly 40% of cases in African countries. The highest mortality rates remain among both children and adults in African countries.SummaryMpox epidemiology has shifted to adults and is affecting relatively few children in the current global outbreak. However, infants, immunocompromised children and African children are still at high risk of severe disease. Mpox vaccines and therapeutic interventions should be accessible to at-risk and affected children globally, especially to those living in endemic African countries.

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“…Their development was incentivized by several “market push-and-pull” mechanisms including the significant public financing of R&D, regulatory incentives, and generous purchase commitments to support stockpiling. They are registered in several HICs; however, despite recurrent outbreaks, they are not available in mpox-endemic African countries (except as an expanded-use programme [ 102 ] and a trial of tecovirimat [ 103 ]). Only when mpox spilled over to HICs and was declared a PHEIC (public health emergency of international concern) did the vaccine and treatments suddenly become available (though still not in African countries).…”

Section: A New Global Approach To Vaccine Research Development and Ma...mentioning

confidence: 99%

The Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs

et al. 2023

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This Review initiates a wide-ranging discussion over 2023 by selecting and exploring core themes to be investigated more deeply in papers submitted to the Vaccines Special Issue on the “Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs”. To tackle the SARS-CoV-2 pandemic, an acceleration of vaccine development across different technology platforms resulted in the emergency use authorization of multiple vaccines in less than a year. Despite this record speed, many limitations surfaced including unequal access to products and technologies, regulatory hurdles, restrictions on the flow of intellectual property needed to develop and manufacture vaccines, clinical trials challenges, development of vaccines that did not curtail or prevent transmission, unsustainable strategies for dealing with variants, and the distorted allocation of funding to favour dominant companies in affluent countries. Key to future epidemic and pandemic responses will be sustainable, global-public-health-driven vaccine development and manufacturing based on equitable access to platform technologies, decentralised and localised innovation, and multiple developers and manufacturers, especially in low- and middle-income countries (LMICs). There is talk of flexible, modular pandemic preparedness, of technology access pools based on non-exclusive global licensing agreements in exchange for fair compensation, of WHO-supported vaccine technology transfer hubs and spokes, and of the creation of vaccine prototypes ready for phase I/II trials, etc. However, all these concepts face extraordinary challenges shaped by current commercial incentives, the unwillingness of pharmaceutical companies and governments to share intellectual property and know-how, the precariousness of building capacity based solely on COVID-19 vaccines, the focus on large-scale manufacturing capacity rather than small-scale rapid-response innovation to stop outbreaks when and where they occur, and the inability of many resource-limited countries to afford next-generation vaccines for their national vaccine programmes. Once the current high subsidies are gone and interest has waned, sustaining vaccine innovation and manufacturing capability in interpandemic periods will require equitable access to vaccine innovation and manufacturing capabilities in all regions of the world based on many vaccines, not just “pandemic vaccines”. Public and philanthropic investments will need to leverage enforceable commitments to share vaccines and critical technology so that countries everywhere can establish and scale up vaccine development and manufacturing capability. This will only happen if we question all prior assumptions and learn the lessons offered by the current pandemic. We invite submissions to the special issue, which we hope will help guide the world towards a global vaccine research, development, and manufacturing ecosystem that better balances and integrates scientific, clinical trial, regulatory, and commercial interests and puts global public health needs first.

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Tecovirimat for Monkeypox in Central African Republic under Expanded Access

Cited by 21 publications

References 3 publications

Poor evidence for an effect of tecovirimat in shortening recovery time in hospitalized mpox cases from real-world data

Poor evidence for an effect of tecovirimat in shortening recovery time in hospitalized mpox cases from real-world data

A global update of mpox (monkeypox) in children

The Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs

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