2023年5月25日，美國食品藥品監督管理局（FDA）批準了口服抗病毒藥物Paxlovid（奈瑪特韋片和利托那韋片，組合包裝供口服使用），用于治療具有進展為重度COVID-19高風險（包括住院或死亡）的輕度至中度COVID-19成人患者。Paxlovid是FDA批準的第四款用于治療成人COVID-19的藥物，也是第一款口服抗病毒藥。
依照緊急使用授權（EUA）生產和包裝并由美國衛生與公眾服務部（DHHS）分發的Paxlovid將繼續提供給成人患者，并確保對此次批準未涵蓋的12-18歲符合條件的兒童進行治療。Paxlovid未被批準或授權用作預防COVID-19的暴露前或暴露后預防藥物。
美國FDA藥品評價與研究中心（CDER）主任Patrizia Cavazzoni表示，“雖然疫情對我們所有人都是一種挑戰，但我們在減輕COVID-19對我們生活的影響方面取得了巨大進展。此次的批準表明，Paxlovid已經達到了美國FDA嚴格的安全性和有效性標準，對于具有進展為重癥高風險的人群（包括先前有免疫力的人群），其仍然是一種重要的治療方案。美國FDA仍然致力于與研發機構合作，促進COVID-19相關的新的預防和治療方案的開發。”
根據《聯邦食品、藥品和化妝品法案》，新藥的批準需要充分的有效性證據和對藥物預期用途的安全性證明。在考慮批準某種藥物時，美國FDA會根據嚴格的科學標準進行受益-風險評估，以確保產品為目標人群帶來的受益大于風險。
Paxlovid的療效主要由EPIC-HR臨床試驗的最終結果支持。EPIC-HR是一項隨機、雙盲、安慰劑對照臨床試驗，對Paxlovid用于治療實驗室確診為SARS-CoV-2感染的非住院有癥狀的成人患者的安全性和有效性進行了研究。入組患者為18歲及以上具有預先設定的發展為重癥的風險因素的成人，如果患者年齡在60歲或以上，則不考慮其是否存在預先設定的慢性疾病。所有入組的患者沒有接種過COVID-19疫苗，之前也沒有感染過COVID-19。28天的隨訪結果表明，與安慰劑對照組相比，在癥狀出現后5天內接受Paxlovid治療的患者（未接受過COVID-19治療性單克隆抗體治療）中，因COVID-19住院或因各種原因死亡（全因死亡）的患者比例顯著降低了86%。在這項研究中（28天的隨訪期），977例患者接受了Paxlovid治療，989例患者接受了安慰劑治療。在Paxlovid治療組中，僅有0.9%的患者因COVID-19住院或因各種原因死亡（全因死亡），相比之下，安慰劑對照組的這一比例達到了6.5%。
Paxlovid（圖片來源：網絡）
Paxlovid的效果在先前有免疫力的患者身上也得到了驗證。在EPIC-HR試驗入組時抗體呈陽性的患者中，在28天隨訪期間，接受Paxlovid治療的490例患者中因COVID-19住院或因各種原因死亡（全因死亡）的風險為0.2%，而接受安慰劑治療的479例患者中的這一比例為1.7%。EPIC-SR是另一項臨床試驗，該項試驗入組了至少具有一個發展為重癥的風險因素且接種過疫苗的患者。雖然沒有統計學意義，但在這些接種過疫苗的患者中，與COVID-19相關住院或全因死亡的風險有所降低。
EPIC-HR和EPIC-SR這兩項隨機對照試驗還提供了關于COVID-19反彈的信息。來自這兩項試驗的數據顯示，SARS-CoV-2（RNA或病毒）脫落或COVID-19癥狀在一小部分患者中出現反彈，且在接受Paxlovid治療和接受安慰劑治療的患者中均有發生。根據美國FDA目前掌握的數據，還沒有明確證據表明Paxlovid治療與COVID-19反彈之間存在關聯。
由于降低與Paxlovid發生顯著藥物相互作用的風險的重要性，Paxlovid緊急使用授權（EUA）的批準標簽和供醫護人員查閱的情況說明書（Fact Sheet）附有黑框警告和處方說明。處方醫師應審查患者服用的所有藥物，以評估潛在的藥物相互作用，并確定患者可能正在服用的其他藥物是否需要調整劑量、中斷和/或額外監測。處方醫師應考慮Paxlovid治療在減少住院和死亡方面的益處，以及是否可以適當管理個體患者的潛在藥物相互作用風險。
美國FDA此次的批準向所有處方醫師提供了正確和安全地開具Paxlovid處方的重要信息，例如劑量說明、潛在副作用以及可能與Paxlovid發生藥物相互作用的藥物的信息。服用Paxlovid最常見的副作用包括味覺受損和腹瀉。患者應就其是否適合服用Paxlovid與醫生進行溝通。
英文原文
Paxlovid manufactured and packaged under the emergency use authorization (EUA) and distributed by the U.S. Department of Health and Human Services will continue to be available to ensure continued access for adults, as well as treatment of eligible children ages 12-18 who are not covered by today’s approval. Paxlovid is not approved or authorized for use as a pre-exposure or post-exposure prophylaxis for prevention of COVID-19.
“While the pandemic has been challenging for all of us, we have made great progress mitigating the impact of COVID-19 on our lives,” said Patrizia Cavazzoni, M.D., director for the FDA’s Center for Drug Evaluation and Research. “Today’s approval demonstrates that Paxlovid has met the agency’s rigorous standards for safety and effectiveness, and that it remains an important treatment option for people at high risk for progression to severe COVID-19, including those with prior immunity. The FDA remains committed to working with sponsors to facilitate the development of new prevention and treatment options for COVID-19.”
Under the Federal Food, Drug, and Cosmetic Act, approval of a new drug requires, among other things, substantial evidence of effectiveness and a demonstration of safety for the drug’s intended use(s). In considering approval of a drug, the FDA conducts a benefit-risk assessment based on rigorous scientific standards to ensure that the product’s benefits outweigh its risks for the intended population.
The efficacy of Paxlovid was primarily supported by the final results of the EPIC-HR clinical trial. EPIC-HR was a randomized, double-blind, placebo-controlled clinical trial studying Paxlovid for the treatment of non-hospitalized symptomatic adults with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Patients were adults 18 years of age and older with a prespecified risk factor for progression to severe disease or were 60 years and older regardless of prespecified chronic medical conditions. All patients had not received a COVID-19 vaccine and had not been previously infected with COVID-19. Paxlovid significantly reduced the proportion of people with COVID-19 related hospitalization or death from any cause through 28 days of follow-up by 86% compared to placebo among patients treated within five days of symptom onset and who did not receive COVID-19 therapeutic monoclonal antibody treatment. In this analysis, 977 patients received Paxlovid, and 989 patients received placebo, and among these patients, 0.9% who received Paxlovid were hospitalized due to COVID-19 or died from any cause during 28 days of follow-up compared to 6.5% of the patients who received the placebo.
Benefit of Paxlovid was observed in patients with prior immunity to the virus that causes COVID-19. Among patients in EPIC-HR who were antibody positive at trial enrollment, the risk of COVID-19-related hospitalization or death from any cause during 28 days of follow-up was 0.2% among the 490 patients treated with Paxlovid compared with 1.7% of the 479 patients receiving placebo. EPIC-SR was another clinical trial that enrolled vaccinated patients with at least one risk factor for progression to severe COVID-19. Although not statistically significant, among these vaccinated patients, there was a reduction in the risk of COVID-19 related hospitalization or death from any cause.
EPIC-HR and EPIC-SR were randomized controlled trials and provide information about COVID-19 rebound. Data from these two trials showed that rebound in SARS-CoV-2 (RNA or virus) shedding or COVID-19 symptoms occurred in a subset of patients and happened in both the patients receiving Paxlovid and the placebo. Based on the data currently available to the FDA, there is not a clear association between Paxlovid treatment and COVID-19 rebound.
Because of the importance of reducing the risk of significant drug-drug interactions with Paxlovid, the approved label and authorized Fact Sheet for Health Care Providers for the Paxlovid EUA come with a boxed warning with instructions for prescribers. Prescribers should review all medications taken by the patient to assess for potential drug-drug interactions and determine if other medicines that a patient may be taking require a dose adjustment, interruption and/or additional monitoring. Prescribers should consider the benefit of Paxlovid treatment in reducing hospitalization and death, and whether the risk of potential drug-drug interactions for an individual patient can be appropriately managed.
In conjunction with today’s approval, the FDA is providing all prescribers with important information for prescribing Paxlovid properly and safely, such as dosing instructions, potential side effects and information regarding drugs that may cause drug-drug interactions with Paxlovid. The most common side effects of taking Paxlovid include impaired sense of taste and diarrhea. Patients should discuss with their health care provider whether Paxlovid is right for them.
來源：European Commission
原文鏈接：https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-antiviral-treatment-covid-19-adults
