臨床試驗的早期結果顯示，針對 I 型病毒，抗病毒藥物 tecovirimat 並不比安慰劑更好。
Mariana Lenharo / 2024年8月16日/新聞/自然
據美國國立衛生研究院 (NIH) 稱，在剛果民主共和國 (DRC) 進行的一項臨床試驗中，藥物 tecovirimat 並沒有加速感染某種猴痘病毒的患者的康復。這種被稱為進化枝 I 的病毒類型已在非洲傳播，被認為比導致 2022 年開始的全球性 mpox 爆發的病毒（被稱為進化枝 II）更具致命性。
Tecovirimat 是一種抗病毒藥物，被用於治療 mpox ，儘管臨床證據有限顯示它可以解決症狀。該藥物最初是為了治療由相關病毒引起的天花而開發的；兩者都是正痘病毒屬的成員。
加拿大溫尼伯馬尼托巴大學病毒學家賈森·金德拉查克 (Jason Kindrachuck) 表示：「這當然不是我們所希望的理想結果」。
I 型病毒在剛果民主共和國和非洲其他國家的傳播促使世界衛生組織 (WHO) 於 8 月 14 日宣布國際關注的突發公共衛生事件——最高警報級別。一天前，總部位於亞的斯亞貝巴的非洲疾病管制與預防中心（非洲疾病預防控制中心）首次因疫情爆發而宣布進入公共衛生緊急狀態。
昨天，瑞典報告了首例感染 I 型菌株（稱為 Ib 型）的病例，科學家在 4 月報告稱，該菌株能夠透過包括性接觸在內的方式更容易在人與人之間傳播。去年之前，I型分支被認為主要透過家庭接觸和接觸受感染的野生動物而傳播。
令人失望的結果
由美國國家衛生研究院位於馬里蘭州貝塞斯達的國家過敏和傳染病研究所 (NIAID) 和剛果民主共和國位於金薩沙的國家生物醫學研究所發起的試驗期間，感染I 型分支的患者服用了tecovirimat 或安慰劑藥丸。美國國家衛生研究院 (NIH) 於 8 月 15 日公佈了初步結果，表示與安慰劑相比，抗病毒藥物並未縮短 mpox 症狀的持續時間。
Mpox 是由猴痘病毒引起的疾病，可導致充滿液體的皮膚傷口、發燒、頭痛，嚴重時甚至導致死亡。
然而值得注意的是，研究參與者的死亡率，無論他們接受的是替考維馬 (Tecovirimat) 還是安慰劑，都低於剛果民主共和國報告的任何類型mpox 的總體死亡率：1.7% 相對於 3.6%。
這可能是因為參與者在試驗期間所受到的照顧。加入組的 597 人均住院至少 14 天，在此期間他們除其他外還接受了營養支持；適當補水；治療其他感染或疾病，包括瘧疾；和心理社會支持。
「照護水平非常高，」NIAID 生物統計學家、該試驗計畫負責人洛里·多德 (Lori Dodd) 說。她補充道，在臨床試驗之外維持高品質的照護可能具有挑戰性，「因此團隊將致力於如何將這種照護模式轉化為在門診和資源有限的環境中康復的mpox患者」。
對特定群體的希望
總部位於紐約市的 tecovirat 製造商 SIGA Technologies 在新聞稿中表示，接受該藥物早期治療的試驗參與者以及患有嚴重疾病的參與者都表現出了「有意義的改善」。但完整數據尚未公佈。多德說，正在對它們進行分析，並正在準備一份手稿，以提交給同行評審的期刊。英國牛津大學傳染病專家皮耶羅·奧利亞羅(Piero Olliaro) 表示：「我們都渴望看到這篇論文，特別是想看看是否有任何群體可以選擇性地接受治療，尤其是愛滋病毒感染者。
在對它們進行分析，並正在準備一份手稿，以提交給同行評審的期刊。英國牛津大學傳染病專家皮耶羅·奧利亞羅(Piero Olliaro) 表示：「我們都渴望看到這篇論文，特別是想看看是否有任何群體可以選擇性地接受治療，尤其是愛滋病毒感染者。
目前尚不清楚試驗結果是否可以推論至 Ib 分支。 Olliaro 說：「目前我們對 Ib 分支了解不多，我們需要對臨床表現和結果進行更多調查，以確定是否需要進行新的臨床試驗」。
Kindrachuck 表示，儘管tecovirimat 的初步結果令人失望，但它們確實指出了這樣一個事實：「如果我們向剛果民主共和國及其他地區提供資源，為I 型mpox 患者提供支持，我們實際上可以提高康復率」 。
尼凱斯·恩登比 (Nicaise Ndembi) ，位於亞的斯亞貝巴的非洲疾病預防控制中心的病毒學家表示，研究結果不會改變對當前疫情的應對計畫，其中包括加強監測、增加實驗室檢測、策略分配可用的有限疫苗劑量以及就採購疫苗進行談判。但他表示，研究結果強調了一個事實，即適當的照護標準對於降低與 mpox 相關的死亡率至關重要。
儘管位於丹麥的海勒魯普的巴伐利亞北歐生物技術公司生產了一種針對 mpox 的疫苗，但在非洲國家基本上無法取得。然而，巴伐利亞公司首席執行官保羅·卓別林 (Paul Chaplin) 向 STAT News 報道稱，歐盟已下訂單向非洲疾病預防控制中心捐贈 175,000 劑疫苗。
doi：https://doi.org/10.1038/d41586-024-02694-x
馬克斯‧科茲洛夫的補充報導。
參考文獻；
- Vakaniaki, E. H. et al. Nature Med. https://doi.org/10.1038/s41591-024-03130-3 (2024).
- Mitjà, O. et al. Lancet 401, 939–949 (2023).
Hopes dashed for drug aimed at monkeypox virus spreading in Africa
Early results from clinical trial show that the antiviral drug tecovirimat is no better than placebo against the clade I virus type.
Mariana Lenharo /16 August 2024 / NEWS / Nature
The drug tecovirimat did not accelerate recovery for people in a clinical trial in the Democratic Republic of the Congo (DRC) who were infected with a concerning type of monkeypox virus, according to the US National Institutes of Health (NIH). The viral type, called clade I, has been spreading across Africa and is thought to be more lethal than the one that caused a global mpox outbreak that began in 2022, known as clade II.
Tecovirimat, an antiviral drug, is used to treat mpox, despite there being limited clinical evidence that it resolves symptoms. The drug was originally developed to treat smallpox, which is caused by a related virus; both are members of the Orthopoxvirus genus.
“These are certainly not the ideal results that we were all hoping for,” says Jason Kindrachuck, a virologist at the University of Manitoba in Winnipeg, Canada.
The spread of clade I in the DRC and other countries in Africa prompted the World Health Organization (WHO) to declare a public health emergency of international concern — its highest level of alert — on 14 August. A day earlier, the Africa Centres for Disease Control and Prevention (Africa CDC), based in Addis Ababa, declared its first-ever public-health emergency over the outbreak.
And yesterday, Sweden reported its first case of a person infected with a strain of clade I, called clade Ib, that scientists reported in April as being able to spread more easily between people, by means including sexual contact. Before last year, clade I was thought to transmit mainly through household contact and through contact with infected wild animals.
Disappointing results
During the trial, launched by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, and the DRC’s National Institute of Biomedical Research in Kinshasa, people infected with clade I were given either tecovirimat or a placebo pill. According to the NIH, which announced early results on 15 August, the antiviral did not reduce the duration of mpox symptoms compared with the placebo.
Mpox, the disease caused by the monkeypox virus, can cause fluid-filled skin lesions, fever, headache and, in severe cases, death.
Significantly, however, the study participants’ mortality rate, regardless of whether they received tecovirimat or placebo, was lower than the overall mortality rate for any type of mpox reported in the DRC: 1.7% versus 3.6%.
This could be because of the care that the participants received during the trial. The 597 people enrolled were hospitalized for at least 14 days, and during this period they received, among other things, nutritional support; proper hydration; treatment for other infections or diseases they had, including malaria; and psychosocial support.
“The level of care was very high,” says Lori Dodd, a biostatistician at the NIAID and a project leader for the trial. Maintaining that high quality of care outside a clinical trial could be challenging, she adds, “so the team will be working on how to translate that care model for people with mpox who are recovering on an outpatient basis and in resource-limited settings”.
Hope for specific groups
The maker of tecovirimat, SIGA Technologies, based in New York City, suggested in a press release that trial participants who had received early treatment with the drug and those who had severe disease had shown a “meaningful improvement”. But the full data have not been released. They are being analysed, and a manuscript is being prepared for submission to a peer-reviewed journal, Dodd says.
“We are all eager to see the paper, in particular to see if there is any group that could be selectively targeted for treatment, especially people with HIV,” says Piero Olliaro, an infectious-disease specialist at the University of Oxford, UK, adding that outcomes for people with advanced HIV who get infected with the monkeypox virus are often poor2.
It’s not yet clear whether the trial results can be extrapolated to clade Ib. “We don’t know a lot about clade Ib for the time being, and we need more investigations into the clinical presentation and outcomes to inform whether new clinical trials are required,” Olliaro says.
Although the preliminary results for tecovirimat are disappointing, Kindrachuck says, they do point to the fact that “if we get resources into the DRC and beyond for support for patients with clade I mpox, we can actually increase recovery”.
Nicaise Ndembi, a virologist at the Africa CDC in Addis Ababa, says that the results do not change the response plan to the current outbreaks, which includes enhancing surveillance, increasing laboratory testing, strategic distribution of the limited vaccine doses available and negotiating the acquisition of more doses. But he says that the findings highlight the fact that an appropriate standard of care is crucial to reducing mortality related to mpox.
Although a vaccine against mpox, made by the biotechnology firm Bavarian Nordic in Hellerup, Denmark, exists, it is largely unavailable in African countries. However, Bavarian’s chief executive, Paul Chaplin, has reported to STAT News that the European Union has placed an order for 175,000 doses to be donated to the Africa CDC.
doi: https://doi.org/10.1038/d41586-024-02694-x
Additional reporting by Max Kozlov.
References
- Vakaniaki, E. H. et al. Nature Med. https://doi.org/10.1038/s41591-024-03130-3 (2024).
- Mitjà, O. et al. Lancet 401, 939–949 (2023).