As it turns out, all the scientists and doctors who insisted that Merck's "revolutionary" COVID drug molnupiravir is extremely safe weren't faithfully adhering to "the science" after all. Because according to a report published Thursday by Barron's, some scientists are worried that the drug - which purportedly cut hospitalizations in half during a study that was cut short - could cause cancer or birth defects.
So much for having a "strong safety profile," as Dr. Scott Gottlieb claimed in an interview on the day Merck first publicized the research.
It's perfectly understandable why Merck might choose to play down this safety risk: assuming it's approved, the drug is widely expected to be one of "the most lucrative drugs ever" - which is one reason why Merck's shares soared into double-digit territory after the announcement.
As we reported earlier this week, Merck and its "partner" Ridgeback Biotherapeutics will profit immensely by charging customers up to 40x what it costs to make the drug, which Ridgeback originally licensed from Emory University for an "undisclosed sum". The drug was developed with funding from the federal government.
According to Barron's, some scientists who have studied the drug believe that its method of suppressing the virus could potentially run amok within the body.
Some scientists who have studied the drug warn, however, that the method it uses to kill the virus that causes Covid-19 carries potential dangers that could limit the drug’s usefulness.
Molnupiravir works by incorporating itself into the genetic material of the virus, and then causing a huge number of mutations as the virus replicates, effectively killing it. In some lab tests, the drug has also shown the ability to integrate into the genetic material of mammalian cells, causing mutations as those cells replicate.
If that were to happen in the cells of a patient being treated with molnupiravir, it could theoretically lead to cancer or birth defects.
In particular, Raymond Schinazi, a professor of pediatrics and the director of biochemical pharmacology at Emory who studied the drug while it was being developed, and published a number of papers on NHC, the compound that's the active ingredient in the drug. He published a paper that showed the drug can produce a reaction like the one described above, and insisted it shouldn't be given to young people - especially pregnant women - without more data.
Schinazi told Barron’s that he did not believe that molnupiravir should be given to pregnant women, or to young people of reproductive age, until more data is available. Merck’s trials of molnupiravir have excluded pregnant women; the scientists running the trial asked male participants to “abstain from heterosexual intercourse” while taking the drug, according to the federal government website that tracks clinical trials.
Barron's even shared a paper published in the Journal of Infectious Diseases in May by Schinazi and scientists at the University of North Carolina which reported that NHC can cause mutations in animal cell cultures in a lab test designed to detect such mutations - something Merck claims it has tested for. The paper's authors concluded that the risks for molnupiravir "may not be zero".
Merck told Barron's that it has run "extensive tests" on animals which it says show that this shouldn't be an issue. "The totality of the data from these studies indicates that molnupiravir is not mutagenic or genotoxic in in-vivo mammalian systems," a Merck spokesman said.
Still, scientists and doctors who have studied NHC say that Merck needs to "be careful," and it's not just Schinazi warning about the drug's potential risks.
Dr. Shuntai Zhou, a scientist at the Swanstrom Lab at UNC, said "there is a concern that this will cause long-term mutation effects, even cancer."
Zhou says that he is certain that the drug will integrate itself into the DNA of mammalian hosts. "Biochemistry won’t lie," he says. "This drug will be incorporated in the DNA."
Merck hasn't yet released any data from its animal studies, but the scientists believe that it would take long-term studies to show that the drug is truly totally safe.
"Proceed with caution and at your own peril," wrote Raymond Schinazi, a professor of pediatrics and the director of the division of biochemical pharmacology at the Emory University School of Medicine, who has studied NHC for decades, in an email to Barron’s.
Analysts are already warning that these questions about the drug's safety suggest the reaction in Merck's shares was a little "overblown", to say the least. Investors apparently were so eager for a new "pandemic panacea" (now that the mRNA jabs have proven to be much less effective than advertised) that they didn't ask too many questions about safety, or even question the paucity of data. One analyst for SVB Leerink Dr. Geoffrey Porges described investors' reaction from Friday as "wishful thinking".
Even once the FDA authorizes the drug, Dr. Porges believes it will come with strict limitations on who can and can't use it. "I think it is effectively going to be a controlled substance", Dr. Porges said, adding that the risks to pregnant women, or women who may soon become pregnant, could present thorny problems for the FDA's advisory committee reviewing the drug.
Given that the safety risks of the drug seem well-documented already, Wall Street's gushing about the drug's prospects - "it really is THAT good",one analyst insisted - seems like an idiotic blunder in retrospect. The product of what one might call "magical thinking".
事實證明，所有堅持認為默克公司的“革命性”COVID 藥物莫努匹拉韋非常安全的科學家和醫生畢竟並沒有忠實於“科學”。因為根據巴倫周刊週四發表的一份報告，一些科學家擔心這種藥物——據稱在一項被縮短的研究期間將住院人數減少了一半——可能會導致癌症或先天缺陷。
正如 Scott Gottlieb 博士在默克首次公佈這項研究的那天接受采訪時所說的那樣，擁有“強大的安全性”就如此。
默克為何選擇淡化這種安全風險是完全可以理解的：假設它獲得批准，人們普遍預計該藥物將成為“有史以來最賺錢的藥物”之一——這也是默克股價在上市後飆升至兩位數的原因之一。公告。
正如我們本週早些時候報導的那樣，默克及其“合作夥伴”Ridgeback Biotherapeutics 將通過向客戶收取高達製造藥物成本 40 倍的費用來獲得巨大利潤，Ridgeback 最初從埃默里大學獲得了“未公開金額”的許可。該藥物是在聯邦政府的資助下開發的。
根據巴倫雜誌的說法，一些研究過這種藥物的科學家認為，它抑制病毒的方法可能會在體內肆虐。
然而，一些研究過這種藥物的科學家警告說，它用來殺死導致 Covid-19 的病毒的方法存在潛在危險，可能會限制該藥物的有效性。
Molnupiravir 的工作原理是將自身整合到病毒的遺傳物質中，然後在病毒複製時引起大量突變，從而有效地殺死它。在一些實驗室測試中，該藥物還顯示出能夠整合到哺乳動物細胞的遺傳物質中，在這些細胞複製時引起突變。
如果這種情況發生在接受莫諾匹韋治療的患者的細胞中，理論上可能會導致癌症或先天缺陷。特別是，埃默里大學兒科教授兼生化藥理學主任雷蒙德·希納齊 (Raymond Schinazi) 在該藥物開發過程中對其進行了研究，並發表了多篇關於 NHC 的論文，NHC 是該藥物的活性成分。他發表了一篇論文，表明這種藥物可以產生上述反應，並堅持認為不應該在沒有更多數據的情況下將其用於年輕人——尤其是孕婦。
Schinazi 告訴《巴倫周刊》，在有更多數據可用之前，他認為不應將莫諾匹韋用於孕婦或育齡年輕人。默克 (Merck) 公司的莫奈拉韋試驗已將孕婦排除在外；根據跟踪臨床試驗的聯邦政府網站，進行試驗的科學家要求男性參與者在服用該藥物時“避免異性性交”。
Barron's 甚至分享了 Schinazi 和北卡羅來納大學的科學家 5 月份在《傳染病雜誌》上發表的一篇論文，該論文報告說 NHC 可以在旨在檢測此類突變的實驗室測試中引起動物細胞培養物中的突變 - 默克聲稱它已經測試了。該論文的作者得出結論，molnupiravir 的風險“可能不是零”。
默克告訴巴倫雜誌，它已經對動物進行了“廣泛的測試”，並表示這應該不是問題。 “這些研究的全部數據表明，molnupiravir 在體內哺乳動物系統中沒有致突變性或基因毒性，”默克公司發言人說。
儘管如此，研究過 NHC 的科學家和醫生表示，默克需要“小心”，這不僅僅是 Schinazi 對這種藥物潛在風險的警告。
UNC Swanstrom 實驗室的科學家 Shuntai Zhou 博士說：“有人擔心這會導致長期的突變效應，甚至癌症。”
周說他確信這種藥物會整合到哺乳動物宿主的 DNA 中。 “生物化學不會撒謊，”他說。 “這種藥物將被納入 DNA。”
默克尚未公佈其動物研究的任何數據，但科學家們認為，需要長期研究才能證明該藥物是真正完全安全的。
“謹慎行事，後果自負，”埃默里大學醫學院兒科教授兼生物化學藥理學部主任雷蒙德·希納齊 (Raymond Schinazi) 在給巴倫雜誌的電子郵件中寫道，他已經研究了 NHC 數十年。
分析師已經警告說，這些關於該藥物安全性的問題表明默克股票的反應至少可以說有點“誇大其詞”。投資者顯然非常渴望一種新的“大流行靈丹妙藥”（現在 mRNA 注射已被證明遠不如宣傳的那樣有效），以至於他們沒有問太多關於安全性的問題，甚至沒有質疑數據的缺乏。 SVB Leerink 的一位分析師 Geoffrey Porges 博士將周五投資者的反應描述為“一廂情願”。
即使 FDA 批准了該藥物，Por 博士
