以膠片和拍立得相機(jī)聞名的日本企業(yè)富士膠片(Fujifilm)并非僅僅出售相機(jī),該集團(tuán)還生產(chǎn)醫(yī)療設(shè)備、抗衰老護(hù)膚品和護(hù)發(fā)品——而現(xiàn)在,它還研發(fā)了一種或可治療新冠病毒的藥物。
二月底,全球的新冠病毒肺炎患者達(dá)到8萬(wàn),世界衛(wèi)生組織尚未宣布新冠肺炎疫情構(gòu)成全球大流行。當(dāng)時(shí),日本衛(wèi)生部長(zhǎng)表示,政府正考慮使用一種名為Avigan(又名Favipiravir,法匹拉韋)的藥物來(lái)治療新冠肺炎患者,富士膠片控股株式會(huì)社的股價(jià)隨后飆升。
一個(gè)多月后,法匹拉韋在兩項(xiàng)新冠肺炎臨床試驗(yàn)中顯示出良好療效,更多迫切尋找治療新冠肺炎“解藥”的國(guó)家,也準(zhǔn)備測(cè)試該藥物的效用。
曾經(jīng)不起眼的藥物突然火了
法匹拉韋由富山化學(xué)工業(yè)株式會(huì)社研發(fā),最初是作為一種抗流感藥物。2014年,日本批準(zhǔn)該藥物上市,可用于流感的臨床治療,屬于日本厚生勞動(dòng)省的儲(chǔ)備藥物。該部門未回復(fù)通過(guò)電郵發(fā)出的置評(píng)請(qǐng)求。
但在新冠肺炎疫情爆發(fā)前,這種藥物一直默默無(wú)聞——人們?cè)谌毡臼袌?chǎng)都買不到這種藥。現(xiàn)在,幾個(gè)國(guó)家正在開(kāi)展臨床試驗(yàn),研究法匹拉韋抗擊新冠病毒的效用,部分報(bào)告顯示其療效良好。
中國(guó)生物技術(shù)發(fā)展中心主任張新民在3月17日表示,對(duì)武漢和深圳的340名患者進(jìn)行試驗(yàn)后發(fā)現(xiàn),法匹拉韋對(duì)抗擊新冠病毒“療效明確”。
張新民介紹,接受法匹拉韋治療的患者與對(duì)照組相比,病毒核酸轉(zhuǎn)陰時(shí)間更短。他還表示,已向新冠肺炎醫(yī)療救治組推薦法匹拉韋。
三天后,印尼總統(tǒng)佐科·“佐科維”·維多多(Joko "Jokowi" Widodo)表示,該國(guó)正在進(jìn)口數(shù)百萬(wàn)片法匹拉韋,用于治療新冠肺炎患者。
3月22日,疫情嚴(yán)重的意大利批準(zhǔn)了一項(xiàng)新的臨床試驗(yàn),研究法匹拉韋治療新冠肺炎的有效性。此外,泰國(guó)一家醫(yī)院也正在研究法匹拉韋等藥物,測(cè)試它們抗擊新冠病毒的療效。
組合療法
同時(shí),中國(guó)研究人員正在為臨床試驗(yàn)招募患者。在3月8日啟動(dòng)的研究中,新冠肺炎患者將分別接受法匹拉韋或一種名為托珠單抗(tocilizumab)的藥物治療,后者通常用于治療類風(fēng)濕性關(guān)節(jié)炎。又或者,他們將接受兩種藥物的組合治療。
生物技術(shù)制藥公司安進(jìn)公司的病毒學(xué)家、全球醫(yī)學(xué)學(xué)習(xí)和療效高級(jí)經(jīng)理里亞茲·阿巴斯認(rèn)為,包含多種抗病毒藥物的組合療法可能會(huì)更有效,因?yàn)檫@樣可降低出現(xiàn)耐藥病毒株的機(jī)會(huì)。
阿巴斯說(shuō):“[法匹拉韋和托珠單抗的試驗(yàn)]將提供一些較好的、更有力的科學(xué)數(shù)據(jù),便于我們對(duì)此作出判斷:對(duì)于新冠肺炎患者來(lái)說(shuō),法匹拉韋是更好的選擇嗎?它管用嗎?如果有用,是單獨(dú)服用,還是聯(lián)合其他藥物服用的療效更好?”
3月23日,托珠單抗獲美國(guó)食品藥品監(jiān)督管理局(FDA)批準(zhǔn)進(jìn)入臨床試驗(yàn),可用于治療住院的新冠肺炎危重癥患者。雖然法匹拉韋在美國(guó)還未被視為治療新冠病毒的潛在藥物并接受有效性試驗(yàn),但FDA在2015年就完成了將其作為抗流感藥物的臨床試驗(yàn)。
政府許可
在任何國(guó)家,全面使用法匹拉韋治療新冠肺炎,都需要得到政府批準(zhǔn)。日本尚未正式批準(zhǔn)該藥物用于治療新冠肺炎,但除了意大利、泰國(guó)和中國(guó)正在進(jìn)行和即將進(jìn)行試驗(yàn)外,該國(guó)于3月也啟動(dòng)了此藥的臨床研究。
阿巴斯認(rèn)為,從武漢和深圳的早期試驗(yàn)結(jié)果來(lái)看,法匹拉韋的表現(xiàn)良好,但在合理確認(rèn)其療效之前,還需要做進(jìn)一步的試驗(yàn)——例如,法匹拉韋與其他藥物的比較、隨機(jī)選擇患者,還有用更大的患者庫(kù)做試驗(yàn)。
富士膠片的發(fā)言人稱:“我們還沒(méi)有公開(kāi)的臨床科學(xué)證據(jù),證明患者使用法匹拉韋對(duì)抗新冠肺炎的有效性和安全性,所以尚且無(wú)法談?wù)摯怂帯!?/p>
競(jìng)爭(zhēng)者
目前,在可治療新冠肺炎的藥物中,法匹拉韋相對(duì)而言并不起眼。
吉利德公司研發(fā)的瑞德西韋(remdesivir)被認(rèn)為是最有潛力的領(lǐng)先藥物。世衛(wèi)組織助理總干事布魯斯·艾爾沃德曾在二月下旬表示:“我們認(rèn)為,目前只有一種藥可能有效,那就是瑞德西韋。”
瑞德西韋是世衛(wèi)組織發(fā)起的“團(tuán)結(jié)試驗(yàn)項(xiàng)目”的四種抗病毒療法之一。該項(xiàng)目于3月18日啟動(dòng),旨在協(xié)調(diào)全球開(kāi)展研究,尋找新冠肺炎的潛在療法。其余三種療法分別是:氯喹;洛匹那韋和利托那韋的組合療法;洛匹那韋、利托那韋和干擾素的組合療法。在這項(xiàng)研究中,患者將接受四種療法的其中一種進(jìn)行治療。
不過(guò),研究中的藥物或會(huì)發(fā)生變化。如果四種療法中有一種沒(méi)有明確療效,就會(huì)被移除,然后添加其他藥物。
阿巴斯說(shuō):“我看好瑞德西韋,這是一種前景良好的藥物。”但他也表示,法匹拉韋的早期臨床試驗(yàn)結(jié)果令人鼓舞。事實(shí)上,法匹拉韋和瑞德西韋有一個(gè)重要的共同特征。新冠病毒利用一種名為RNA聚合酶的酶進(jìn)行自我復(fù)制,而有的抗病毒藥物可通過(guò)抑制這種復(fù)制來(lái)發(fā)揮效用,從而阻止病毒繁殖。瑞德西韋和法匹拉韋都屬于此類藥物。
阿巴斯認(rèn)為,作為聚合酶抑制劑,瑞德西韋和法匹拉韋是同一類藥物。“(但)沒(méi)有兩種藥物是相同的,所以我們必須對(duì)它們進(jìn)行測(cè)試。”
他補(bǔ)充說(shuō),此外還有一大挑戰(zhàn),即如果世衛(wèi)組織的研究和正在進(jìn)行的其他試驗(yàn)表明瑞德西韋有效,那么如何獲得瑞德西韋將帶來(lái)“巨大”壓力。阿巴斯說(shuō),吉列德的這種藥物通過(guò)靜脈輸液給藥,因而比片劑更難生產(chǎn),成本也更高,而且還需要在醫(yī)院給藥。
阿巴斯認(rèn)為,“法匹拉韋的顯著優(yōu)勢(shì)在于,它是一種藥片,更容易生產(chǎn),成本也更低”,因此更容易實(shí)現(xiàn)量產(chǎn)。“很明顯,我們正急需藥物,”他說(shuō)。(財(cái)富中文網(wǎng))
譯者:Emily
以膠片和拍立得相機(jī)聞名的日本企業(yè)富士膠片(Fujifilm)并非僅僅出售相機(jī),該集團(tuán)還生產(chǎn)醫(yī)療設(shè)備、抗衰老護(hù)膚品和護(hù)發(fā)品——而現(xiàn)在,它還研發(fā)了一種或可治療新冠病毒的藥物。
二月底,全球的新冠病毒肺炎患者達(dá)到8萬(wàn),世界衛(wèi)生組織尚未宣布新冠肺炎疫情構(gòu)成全球大流行。當(dāng)時(shí),日本衛(wèi)生部長(zhǎng)表示,政府正考慮使用一種名為Avigan(又名Favipiravir,法匹拉韋)的藥物來(lái)治療新冠肺炎患者,富士膠片控股株式會(huì)社的股價(jià)隨后飆升。
一個(gè)多月后,法匹拉韋在兩項(xiàng)新冠肺炎臨床試驗(yàn)中顯示出良好療效,更多迫切尋找治療新冠肺炎“解藥”的國(guó)家,也準(zhǔn)備測(cè)試該藥物的效用。
曾經(jīng)不起眼的藥物突然火了
法匹拉韋由富山化學(xué)工業(yè)株式會(huì)社研發(fā),最初是作為一種抗流感藥物。2014年,日本批準(zhǔn)該藥物上市,可用于流感的臨床治療,屬于日本厚生勞動(dòng)省的儲(chǔ)備藥物。該部門未回復(fù)通過(guò)電郵發(fā)出的置評(píng)請(qǐng)求。
但在新冠肺炎疫情爆發(fā)前,這種藥物一直默默無(wú)聞——人們?cè)谌毡臼袌?chǎng)都買不到這種藥。現(xiàn)在,幾個(gè)國(guó)家正在開(kāi)展臨床試驗(yàn),研究法匹拉韋抗擊新冠病毒的效用,部分報(bào)告顯示其療效良好。
中國(guó)生物技術(shù)發(fā)展中心主任張新民在3月17日表示,對(duì)武漢和深圳的340名患者進(jìn)行試驗(yàn)后發(fā)現(xiàn),法匹拉韋對(duì)抗擊新冠病毒“療效明確”。
張新民介紹,接受法匹拉韋治療的患者與對(duì)照組相比,病毒核酸轉(zhuǎn)陰時(shí)間更短。他還表示,已向新冠肺炎醫(yī)療救治組推薦法匹拉韋。
三天后,印尼總統(tǒng)佐科·“佐科維”·維多多(Joko "Jokowi" Widodo)表示,該國(guó)正在進(jìn)口數(shù)百萬(wàn)片法匹拉韋,用于治療新冠肺炎患者。
3月22日,疫情嚴(yán)重的意大利批準(zhǔn)了一項(xiàng)新的臨床試驗(yàn),研究法匹拉韋治療新冠肺炎的有效性。此外,泰國(guó)一家醫(yī)院也正在研究法匹拉韋等藥物,測(cè)試它們抗擊新冠病毒的療效。
組合療法
同時(shí),中國(guó)研究人員正在為臨床試驗(yàn)招募患者。在3月8日啟動(dòng)的研究中,新冠肺炎患者將分別接受法匹拉韋或一種名為托珠單抗(tocilizumab)的藥物治療,后者通常用于治療類風(fēng)濕性關(guān)節(jié)炎。又或者,他們將接受兩種藥物的組合治療。
生物技術(shù)制藥公司安進(jìn)公司的病毒學(xué)家、全球醫(yī)學(xué)學(xué)習(xí)和療效高級(jí)經(jīng)理里亞茲·阿巴斯認(rèn)為,包含多種抗病毒藥物的組合療法可能會(huì)更有效,因?yàn)檫@樣可降低出現(xiàn)耐藥病毒株的機(jī)會(huì)。
阿巴斯說(shuō):“[法匹拉韋和托珠單抗的試驗(yàn)]將提供一些較好的、更有力的科學(xué)數(shù)據(jù),便于我們對(duì)此作出判斷:對(duì)于新冠肺炎患者來(lái)說(shuō),法匹拉韋是更好的選擇嗎?它管用嗎?如果有用,是單獨(dú)服用,還是聯(lián)合其他藥物服用的療效更好?”
3月23日,托珠單抗獲美國(guó)食品藥品監(jiān)督管理局(FDA)批準(zhǔn)進(jìn)入臨床試驗(yàn),可用于治療住院的新冠肺炎危重癥患者。雖然法匹拉韋在美國(guó)還未被視為治療新冠病毒的潛在藥物并接受有效性試驗(yàn),但FDA在2015年就完成了將其作為抗流感藥物的臨床試驗(yàn)。
政府許可
在任何國(guó)家,全面使用法匹拉韋治療新冠肺炎,都需要得到政府批準(zhǔn)。日本尚未正式批準(zhǔn)該藥物用于治療新冠肺炎,但除了意大利、泰國(guó)和中國(guó)正在進(jìn)行和即將進(jìn)行試驗(yàn)外,該國(guó)于3月也啟動(dòng)了此藥的臨床研究。
阿巴斯認(rèn)為,從武漢和深圳的早期試驗(yàn)結(jié)果來(lái)看,法匹拉韋的表現(xiàn)良好,但在合理確認(rèn)其療效之前,還需要做進(jìn)一步的試驗(yàn)——例如,法匹拉韋與其他藥物的比較、隨機(jī)選擇患者,還有用更大的患者庫(kù)做試驗(yàn)。
富士膠片的發(fā)言人稱:“我們還沒(méi)有公開(kāi)的臨床科學(xué)證據(jù),證明患者使用法匹拉韋對(duì)抗新冠肺炎的有效性和安全性,所以尚且無(wú)法談?wù)摯怂帯!?/p>
競(jìng)爭(zhēng)者
目前,在可治療新冠肺炎的藥物中,法匹拉韋相對(duì)而言并不起眼。
吉利德公司研發(fā)的瑞德西韋(remdesivir)被認(rèn)為是最有潛力的領(lǐng)先藥物。世衛(wèi)組織助理總干事布魯斯·艾爾沃德曾在二月下旬表示:“我們認(rèn)為,目前只有一種藥可能有效,那就是瑞德西韋。”
瑞德西韋是世衛(wèi)組織發(fā)起的“團(tuán)結(jié)試驗(yàn)項(xiàng)目”的四種抗病毒療法之一。該項(xiàng)目于3月18日啟動(dòng),旨在協(xié)調(diào)全球開(kāi)展研究,尋找新冠肺炎的潛在療法。其余三種療法分別是:氯喹;洛匹那韋和利托那韋的組合療法;洛匹那韋、利托那韋和干擾素的組合療法。在這項(xiàng)研究中,患者將接受四種療法的其中一種進(jìn)行治療。
不過(guò),研究中的藥物或會(huì)發(fā)生變化。如果四種療法中有一種沒(méi)有明確療效,就會(huì)被移除,然后添加其他藥物。
阿巴斯說(shuō):“我看好瑞德西韋,這是一種前景良好的藥物。”但他也表示,法匹拉韋的早期臨床試驗(yàn)結(jié)果令人鼓舞。事實(shí)上,法匹拉韋和瑞德西韋有一個(gè)重要的共同特征。新冠病毒利用一種名為RNA聚合酶的酶進(jìn)行自我復(fù)制,而有的抗病毒藥物可通過(guò)抑制這種復(fù)制來(lái)發(fā)揮效用,從而阻止病毒繁殖。瑞德西韋和法匹拉韋都屬于此類藥物。
阿巴斯認(rèn)為,作為聚合酶抑制劑,瑞德西韋和法匹拉韋是同一類藥物。“(但)沒(méi)有兩種藥物是相同的,所以我們必須對(duì)它們進(jìn)行測(cè)試。”
他補(bǔ)充說(shuō),此外還有一大挑戰(zhàn),即如果世衛(wèi)組織的研究和正在進(jìn)行的其他試驗(yàn)表明瑞德西韋有效,那么如何獲得瑞德西韋將帶來(lái)“巨大”壓力。阿巴斯說(shuō),吉列德的這種藥物通過(guò)靜脈輸液給藥,因而比片劑更難生產(chǎn),成本也更高,而且還需要在醫(yī)院給藥。
阿巴斯認(rèn)為,“法匹拉韋的顯著優(yōu)勢(shì)在于,它是一種藥片,更容易生產(chǎn),成本也更低”,因此更容易實(shí)現(xiàn)量產(chǎn)。“很明顯,我們正急需藥物,”他說(shuō)。(財(cái)富中文網(wǎng))
譯者:Emily
Japanese conglomerate Fujifilm, most famous for its film and instant cameras, does more than sell point-and-shoots: it also makes medical equipment, anti-aging skincare, hair products—and now a potential coronavirus treatment.
In late February, when the coronavirus had sickened 80,000 people worldwide—on Friday the total topped 530,000—and the World Health Organization had not yet declared a pandemic,?shares in Fujifilm Holdings Corp soared after Japan's health minister said the government was considering using a drug called Avigan, also known as favipiravir, to treat patients sickened by COVID-19.
More than a month later, favipiravir has showed promise in two trials involving coronavirus patients, with more countries, all desperate for an answer to COVID-19, prepare to test its effectiveness.
An obscure drug—until now
Favipiravir initially was developed by Fujifilm Toyama Chemical as an anti-influenza drug. Japan approved it for clinical use in treating influenza in 2014. Japan's Ministry of Health, Labour, and Welfare—which did not respond to an emailed request for comment—maintains a stockpile of favipiravir.
Yet the drug remained relatively obscure—it's not available on the market in Japan—until the coronavirus outbreak. Now, clinical trials in several countries are studying favipiravir's effectiveness in combatting COVID-19, with some already reporting good results.
Trials done with 340 patients in the Chinese cities of Wuhan and Shenzhen found that favipiravir was "clearly effective in treatment" of COVID-19 Zhang Xinmin, the director of the China National Center for Biotechnology Development?said on March 17.
Zhang said patients who received favipiravir tested negative for the virus in a shorter period of time than patients in the control group, and said favipiravir has been recommended to medical teams treating COVID-19.
Three days later, Indonesian President Joko "Jokowi" Widodo said his country was importing millions of doses of Avigan to treat COVID-19 patients.
Authorities in Italy, which has been badly hit by the coronavirus pandemic, approved new clinical trials to study favipiravir as a COVID-19 treatment on March 22. And a hospital in Thailand is launching a study of several drugs, including favipiravir, to test their efficacy in treating COVID-19.
Combination treatments
Researchers in China, meanwhile, are currently recruiting for clinical trials where COVID-19 patients will take either favipiravir, a drug called tocilizumab—normally used to treat rheumatoid arthritis—or a combination of the two. That study launched on March 8.
Combination treatments with more than one antiviral can be more effective, in part because they lower the chances of drug-resistant virus strains, said Riaz Abbas, a virologist and senior manager of global medical learning and performance at biotech pharmaceutical company Amgen.
"[The favipiravir and tocilizumab trials] would help give us some good and more robust scientific data to say okay, so is favipiravir a better option for patients with COVID-19? Does it work, yes or no? And if it works, does it work better on its own or in combination?" Abbas said.
On March 23, the U.S. Food and Drug Administration approved tocilizumab for a clinical trial to treat hospitalized patients with severe COVID-19 pneumonia. Favipiravir has not been trialled in the U.S. as a potential coronavirus treatment, but the FDA did complete a clinical trial on it in 2015 as an anti-flu drug.
The government go-ahead
Government approval is required for full-scale use of favipiravir to treat COVID-19 in any country. Japan has not officially approved the drug to treat COVID-19, but clinical research on its efficacy started there in March in addition to the ongoing and upcoming trials in Italy, Thailand, and China.
The early trials in Wuhan and Shenzhen are promising, but more robust trials are needed—for example, comparing favipiravir to other drugs, randomizing the selection of patients, and using a larger patient pool—before favipiravir's efficacy can be properly determined, Abbas said.
"We have no public clinical scientific evidence yet proving the efficacy and safety of Avigan against COVID-19 in patients, so we cannot talk about Avigan at this moment," a Fujifilm spokesperson said.
Antiviral contenders
For now, favipiravir is a relative underdog among the antivirals that could treat COVID-19.
The frontrunner is Gilead's remdesivir, which is?thought to have the most potential. "There is only one drug right now that we think may have real efficacy and that's remdesivir," WHO assistant director-general Bruce Aylward said in late February.
Remdesivir is one of four treatments in the WHO's "solidarity trial" of antiviral drugs, launched on March 18 to coordinate global studies on potential treatments for the disease. The other three are chloroquine; a combination of lopinavir and ritonavir; and a combination of lopinavir, ritonavir, and interferon beta. Patients in the study will receive one of the four options.
The drugs included in the study, though, are subject to change. If one of the four options has no clear effect, it can be removed from the study, and different drugs can be added.
"My money is on remdesivir. It is quite a promising drug," Abbas said. But early clinical trial results on favipiravir are encouraging, he said. In fact, favipiravir and remdesivir share an important trait. The coronavirus uses an enzyme called RNA polymerase to replicate itself. Some antiviral drugs work by inhibiting this replication so that the virus cannot multiply. Remdesivir is one such drug; so is favipiravir.
As polymerase inhibitors, remdesivir and favipiravir are the same class of drug, Abbas said. "[But] no two drugs are the same, so we have to test them."
One challenge, he adds, is that if the WHO study and other ongoing trials show that remdesivir works, there will be "huge" pressure to access remdesivir. The Gilead drug is administered through intravenous infusion, which Abbas said is harder and costlier to produce than tablets, and also needs to be administered in a hospital.
"Some of the significant advantage of favipiravir is that it's a tablet, so it's easier to make and cheaper to make," and thus easier to scale, Abbas said. "We're in desperate need of medication, that's pretty clear."