即使在發布猴痘之緊急聲明後也很難獲得 TPOXX
資料來源：珍妮 .布萊爾 / 2022 年 8 月 9 日 / Medscape / 葉財團法人台灣紅絲帶基金會編譯
8 月 4 日，美國衛生與公眾服務部部長澤維爾·貝塞拉宣布猴痘為突發公共衛生事件。期待已久的公告遵循了世界衛生組織以及加利福尼亞州、伊利諾伊州和紐約州樹立的榜樣。
但這顯然不足以讓人們更容易獲得美國食品和藥物管理局 (FDA) 批准的抗病毒藥物 tecovirimat (TPOXX)，根據與 Medscape Medical 交談的非營利性健康合作夥伴的政府關係和政策提供者 Garrett Wilkinson出席發布會後表示。
Tecovirimat 被開發和批准用於治療天花，美國在國家戰略儲備 (SNS) 中擁有 170 萬個療程。疾病控制和預防中心 (CDC) 免費提供治療相關猴痘病毒的服務，該中心表示可考慮在患有嚴重疾病或有患嚴重疾病風險的人中使用 tecovirimat。
儘管如此，根據患者和倡導者的新聞和社交媒體表述，這種藥物可能很難獲得。 CDC 要求希望開具該藥物的醫療保健提供者透過擴展的研究性新藥 (EA-IND) 協議提供大量的文書工作和文件。
儘管該機構在 7 月下旬簡化了 EA-IND（也稱為「有同情心的使用」）協議，但與直接從藥店購買 tecovirimat 相比，它對提供者來說仍然更加繁重。
結果導致了延誤，有時甚至完全缺乏可用性。
威爾金森在簡報會前一天接受採訪時說：「醫生能在仿單核准適應症外開藥。他們必須進行研究藥物協議才能獲得 TPOXX 的唯一原因是因為它完全被保存在國家戰略儲備中」。 .
他是許多敦促聯邦政府放寬取得的活動家和研究人員之一。
威爾金森補充說：「讓醫生在公共衛生危機期間填寫大量聯邦文書來開出 FDA 完全批准並認為安全的藥物是荒謬的」。
貝塞拉部長可以透過《聯邦食品、藥品和化妝品法》第 564 條聲明該藥物的緊急使用授權 (EUA) 是適當的。為 tecovirimat 制定 EUA 將減輕供應商與透過擴展的研究性新藥協議（IND）相關的負擔。
但據《華盛頓郵報》和 Axios 報導，週四的公告宣布了公共衛生緊急事件。
這是基於《公共衛生服務法》第 319 條的不同行動，並不賦予 FDA 宣布 EUA 的權利。
「他們在簡報中沒有給出任何跡象表明 IND 會消失」，威爾金森告訴 Medscape。
美國於 5 月 18 日出現了首例猴痘病例。根據 CDC 的數據，截至 8 月 3 日，美國已發現 6,617 例病例。
大量的 Tecovirimat——為政府服務
總部位於紐約市的 SIGA公司 在 2001 年 9/11 襲擊事件後開發了 tecovirimat，據該公司首席科學家丹尼斯·赫魯比 (Dennis Hruby) 說，他在 HHS 宣布之前與 Medscape 交談過。
憑藉數百名健康成人的安全性數據以及猴痘在非人類靈長類動物中的療效數據，該藥物於 2018 年獲得 FDA 批准用於治療天花。
SIGA 首席執行官菲利普·戈麥斯 (Phillip Gomez) 表示，美國自 2013 年以來就儲存了這種藥物，隨著最老的批次達到 7 年的保存期限，該公司正在重新供應國家戰略儲備（SNS）。他說，該公司在 2020-2021 年向美國提供了 363,000 療程，並且每年可以將這一數字增加到 500,000 療程以上。
現在，該公司正在啟動臨床試驗，並準備根據需要提高產量，Hruby 說。
但是，儘管已獲得 FDA 批准且數量豐富，但該藥物對於供應商和患者來說仍然是一個挑戰。但這在其他國家是沒有的情況，該藥物於 2022 年獲得歐洲藥品管理局的許可用於治療猴痘，並且在英國也被批准用於猴痘。
Hruby 說 SIGA 還向加拿大提供藥物，並正在努力回應「來自全球的詢問」，以了解該藥物的同情使用療程。
該公司很清楚美國的瓶頸。
「我認為受影響的社區有很多挫敗感」，戈麥斯說。「他們無法像他們希望的那樣快速和迅速地獲得這種藥物」。
Gomez 說，TPOXX 一直打算出售給政府，以便在爆發時持有，並帶有為國家戰略儲備量身定制的標籤和製造系統。
「忠於官僚主義」
約翰霍普金斯大學彭博公共衛生學院健康安全中心的高級學者 Amesh Adalja 博士在 HHS 宣布之前與 Medscape 進行了交談.
Paxlovid 未經 FDA 批准，但其 EUA 允許醫生為 COVID-19開處方。此外，在 2009 年 H1N1 流感爆發期間，未經批准的靜脈注射 (IV) 帕拉米韋（peramivir）在 EUA 下很容易獲得。
「有了 TPOXX，這個優先層級似乎不存在，因為它們實際上設置了障礙」，Adalja 說。「它們在邏輯上不一致」。
「瓶頸不是 TPOXX 的供應。瓶頸是政府為了開處方而製定的要求」，Adalja 補充說。「我們在這次猴痘爆發中看到的是對官僚機構的忠誠，而不是真正採取正確的行動」。
7月15日，相關專家組致函HHS、CDC、FDA。簽名者包括來自 HIV 倡導組織 PrEP4ALL、Partners in Health 的代表，以及紐約大學和康乃爾大學威爾醫學院的研究人員和醫生。
在信中，簽名者要求 CDC 撤銷其 IND 要求，即從國家戰略儲備中釋放 TPOXX——或者 FDA 通過 EUA 程序授權 TPOXX 用於猴痘。
兩者似乎都還沒有發生。
安全性和有效性數據可用但不完整
威爾金森說，健康合作夥伴認識到有必要收集有關 TPOXX 治療猴痘的人類數據。
「但正如我們幾週來告訴白宮的那樣」，他說，「這應該在正式臨床試驗的背景下進行，而不是在不必要地延遲患者獲得治療的研究藥物方案中進行」。
Gomez 說，兩項關於 tecovirimat 治療猴痘功效的研究正在中非共和國和剛果民主共和國進行。 Hruby 補充說，安慰劑對照試驗將在幾週內在美國、加拿大和歐洲開始招募，中期數據預計將在秋季晚些時候公佈。
該公司還在國防部資助的健康志願者中開展了兩項研究，這兩項研究都早於當前的疫情。 Hruby 說，結果可能允許 SIGA公司尋求使用該藥物進行暴露後預防的適應症。
他說：「我們正在盡最大努力讓我們工作了這麼多年的這種藥物 [獲得] 批准在需要它的人手中」。 「我們將支持這樣做的任何努力」。
截至發稿時，HHS 和 CDC 尚未回應置評請求。
已獲得 FDA 批准的注射用青蒿琥酯版本已經可取得，自 9 月 30 日起，CDC 將不再提供未經 FDA 批准的青蒿琥酯。
Jenny Blair，醫師，亦是佛蒙特州的一名記者、作家和編輯。
TPOXX Hard to Obtain Even After Monkeypox Emergency Declaration
Jenny Blair / August 09, 2022 / Medscape
On August 4, US Department of Health and Human Services Secretary Xavier Becerra declared monkeypox a public health emergency. The long-anticipated announcement followed the examples set by the World Health Organization and the states of California, Illinois, and New York.
But that’s apparently not enough to ease access to the US Food and Drug Administration (FDA)–approved antiviral drug tecovirimat (TPOXX), according to Garrett Wilkinson, a government relations and policy offer with the nonprofit Partners in Health, who spoke to Medscape Medical News after attending the briefing.
Tecovirimat was developed and approved to treat smallpox, and the United States holds 1.7 million courses in the Strategic National Stockpile (SNS). It is available free of charge to treat the related virus monkeypox through the Centers for Disease Control and Prevention (CDC), which has stated that tecovirimat may be considered in people who have or are at risk for severe disease.
Despite that, the drug can be hard to access, according to news and social media accounts by patients and advocates. The CDC requires healthcare providers wishing to prescribe the drug to provide extensive paperwork and documentation through an expanded access investigational new drug (EA-IND) protocol.
Though the agency simplified the EA-IND (also called “compassionate use”) protocol in late July, it is still more burdensome for providers than if tecovirimat were available from pharmacies.
The result has caused delays and sometimes even outright lack of availability.
“Physicians are able to prescribe medication off-label. The only reason they’re having to do an investigational drug protocol to access TPOXX is because it’s being held entirely in the Strategic National Stockpile,” said Wilkinson in an interview the day before the briefing.
He is among a number of activists and researchers who have urged the federal government to ease access.
“It’s absurd to make doctors fill out mountains of federal paperwork during a public health crisis to prescribe a drug the FDA has fully approved and deemed safe,” Wilkinson added.
Secretary Becerra can declare that an emergency use authorization (EUA) for the drug is appropriate through section 564 of the Federal Food, Drug, and Cosmetic Act. Having an EUA for tecovirimat would ease the IND-related burden on providers.
But Thursday’s announcement declared a public health emergency, according to the Washington Post and Axios .
That is a different action based on section 319 of the Public Health Service Act and does not entitle the FDA to declare an EUA.
“They didn’t give any indication [during the briefing] that that IND would go away,” Wilkinson told Medscape.
The US marked its first case of monkeypox on May 18.. As of August 3, the US has seen 6617 cases, according to the CDC.
Plenty of Tecovirimat — for the Government
New York City–based SIGA developed tecovirimat after the 9/11 attacks in 2001, according to the company’s chief scientific officer Dennis Hruby, who spoke to Medscape prior to the HHS announcement.
With safety data in hundreds of healthy adults as well as efficacy data for monkeypox in nonhuman primates, the drug earned FDA approval in 2018 for the treatment of smallpox.
The US has stockpiled the drug since 2013, said Phillip Gomez, SIGA’s chief executive officer, and the company is resupplying the SNS as the oldest batches hit their 7-year expiration date. The company delivered 363,000 courses to the US in 2020-2021, he said, and it can increase that number to more than 500,000 courses a year.
Now, the company is starting up clinical trials and ready to ramp up production as needed, Hruby said.
But despite being FDA-approved and abundant, the drug remains a challenge for providers and patients to access. This isn’t the case in other countries. The drug was licensed in 2022 by the European Medicines Agency to treat monkeypox and is also approved for monkeypox in the United Kingdom.
Hruby said SIGA also supplies Canada and is working to respond to “inquiries from around the globe” for compassionate-use courses of the drug.
The company is well aware of the US bottlenecks.
“I think there’s a lot of frustration in the impacted communities,” Gomez said. “They haven’t been able to access the drug as fast and as speedy as they would have liked.”
TPOXX was always intended to be sold to governments to hold in the event of an outbreak, Gomez said, with a label and manufacturing system tailored to the SNS.
‘Loyalty to Bureaucracy’
There is precedent for easier access to medications during outbreaks — including those without FDA approval, according to Dr Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security at the Bloomberg School of Public Health, who spoke with Medscape before the HHS announcement.
Paxlovid is not FDA-approved, but its EUA allows physicians to prescribe it for COVID-19. Moreover, during the 2009 H1N1 influenza outbreak, unapproved intravenous (IV) peramivir was made readily available under an EUA.
“With TPOXX, that priority just seems to not be there, because they actually erect barriers,” Adalja said. “They’re not logically consistent.”
“The bottleneck is not supply of TPOXX. The bottleneck is the requirements that government has put in place in order to prescribe it,” Adalja added. “What we’ve seen in this monkeypox outbreak is a lot more loyalty to bureaucracy than to actually taking the correct action.”
On July 15, a group of concerned experts sent a letter to HHS, CDC, and FDA. The signers included representatives from the HIV advocacy organization PrEP4ALL, Partners in Health, and researchers and physicians at New York University and Weill Cornell Medicine.
In the letter, the signers asked that CDC rescind its IND requirement to release TPOXX from the national stockpile — or that FDA authorize TPOXX for monkeypox through the EUA process.
Neither appears to have yet occurred.
Safety and Efficacy Data Are Available but Incomplete
Partners in Health recognizes the need to collect human data on the efficacy of TPOXX for monkeypox, Wilkinson said.
“But as we’ve told the White House for weeks,” he said, “this should be done in the context of a formal clinical trial, not an investigational drug protocol that needlessly delays patient access to treatment.”
Two studies of tecovirimat’s efficacy to treat monkeypox are under way, in the Central African Republic and the Democratic Republic of the Congo, according to Gomez. Placebo-controlled trials will begin enrollment in the US, Canada, and Europe within a few weeks, Hruby added, with interim data expected by late fall.
The company is also running a pair of studies funded by the Department of Defense in healthy volunteers, both of which predated the current outbreak. Results may allow SIGA to seek an indication to use the drug for postexposure prophylaxis, Hruby said.
“We’re doing our very best to get this drug we worked so many years [to get] approved in the hands of the people who need it,” he said. “We’ll support any efforts to do that.”
HHS and CDC had not responded to requests for comment by press time.
An FDA-approved version of injectable artesunate is available, and the CDC will no longer be providing non–FDA-approved artesunate as of September 30.
Jenny Blair, MD, is a journalist, writer, and editor in Vermont.