人類處方藥物｜對抗全球衛生的安全威脅 Combating a threat to global health security
全人類正面臨一個危及公共衛生的嚴重威脅。原本被視為已受控制的感染疾病，甚至常規手術，都可能因為細菌對抗生素的抗藥性越來越強，再度成為危及生命的威脅。因此，百靈佳殷格翰正協助領導抗擊這些「超級細菌」的戰鬥。
但凡殺不死的，將使之更強大（What doesn’t kill you makes you stronger）。或許聽起來像流傳已久的至理名言，卻巧妙地描述了過去幾十年裡，微小的病原性細菌如何透過對抗生素產生抗藥性，變得更加致命的進程。
對於醫生和病患而言，這個情況可能始於一個無心之舉：一位病患服用抗生素來對抗細菌感染，但在感覺好轉後就停止治療，讓特別具抗藥性的細菌存活下來，這些倖存的細菌便有機會在病患體內繁殖和蔓延，再傳染給其他人。當情況屢次發生，這種細菌將對最初用來殺死它的抗生素產生抗藥性，最終，成為了超級細菌。
微生物抗藥性（Antimicrobial Resistance；簡稱AMR）正以前所未有的速度發展，世界衛生組織將其稱為「全球健康的最大威脅」。目前，每年有超過120萬人死於微生物抗藥性，聯合國預測這個數字到了2050年，可能會超過1000萬。
微生物抗藥性使創傷、切口以及糖尿病等常見疾病的相關併發症更加危險，甚至影響剖腹產、髖關節置換術等常規手術，變成危及生命的行動。
這股威脅日益增加，百靈佳殷格翰將在全球迎擊微生物抗藥性的戰役上扮演領導的角色，透過資助合作夥伴，實現更精確、更科學化的方法來診治細菌感染。
造成該現象的原因
微生物抗藥性的增加有多種原因，其中最主要的原因是約有50%的病患，被開立了不一定需要的抗生素處方。隨著服用次數增加，使多種細菌與抗生素接觸，便有機會發展抗藥性。
此外，在家畜的飼養上廣泛使用四環素類抗生素（Broad-spectrum antibiotic）也是造成這個趨勢的主因之一。多年來，百靈佳殷格翰一直致力研究如何防止抗藥性產生的方式，將抗生素施用於家畜身上。
然而，這個威脅仍持續影響著全世界，國際抗微生物抗藥性協調小組（Interagency Coordination Group on Antimicrobial Resistance, IACG）在2019年向聯合國秘書長提交的報告，呼籲對微生物抗藥性採取緊急行動：「現在已經沒有時間可以浪費了，除非全世界採取緊急行動，否則微生物抗藥性，將對未來世代產生災難性的影響。」
邁向更精確的診斷
2022年6月，百靈佳殷格翰與生物科技公司Evotec和bioMérieux合資成立了Aurobac Therapeutics SAS，該企業的目標是開發有效抗菌物質、修改治療方案，同時減少微生物抗藥性的風險，以應對這艱難挑戰。
現代醫學通常以廣效抗生素（Broad-spectrum antibiotic）來治療各種感染，而廣效抗生素正如其名，並非針對特定的細菌。
「我們想要改變當前治療方案中，過度依賴廣效抗生素的相關策略。」 百靈佳殷格翰的創新主管、董事會成員之一的Michel Pairet表示：「目標是將其轉變為精密醫療。」
這個過程將從詳細診斷出病原體，並對其特性的分析開始，找到病徵對應的細菌後，病患將能接受精確的抗生素治療。
「Aurobac在微生物抗藥性的戰役中扮演著非常重要的角色。」－ Michel Pairet
「我們採用modality-agnostic的方法，非常適合標靶性抗生素的開發。」－Werner Lanthaler
「我們在這個合資企業中的角色，是開發與商業化診斷測試。」－Alexandre Mérieux
約50% 的人被開立抗生素處方時其實不一定需要使用抗生素 (來源)
一支專業知識互補的強大團隊
Aurobac的志業是將抗生素的使用方式轉換。其中，百靈佳殷格翰提供了這家總部位於里昂的合資企業4,000萬歐元資金中的3,000萬歐元，成為主要投資者，Evotec和bioMérieux則分別投入了500萬歐元。三方夥伴將結合各自的專業知識，共同開拓全新的研究項目。
BioMérieux擁有抗微生物抗藥性診斷的豐富專業知識，並提供了一系列全面的綜合診斷解決方案，有助於醫護人員精選使用抗生素的治療。「我們在這個合資企業中的角色，是開發與商業化診斷測試，這也包含了『伴隨式診斷（companion diagnostics）』的開發，將有助於病患配對特定的藥物。」bioMérieux董事長兼執行長Alexandre Mérieux說道。
Evotec則提供了一個在對抗傳染疾病上領先全球的平台。該公司有200多名研究人員在研究新型抗感染藥物上，具有處理多種物質類別的廣泛專業知識與經驗。Evotec執行長Werner Lanthaler表示：「在Evotec，我們採用modality-agnostic的方法，非常適合標靶性抗生素的開發，這為Aurobac提供了所需的平台，並透過新的途徑和物質成功對抗微生物抗藥性。」
抗微生物抗藥性為何產生和擴散
不當使用抗生素治療感冒和流感等疾病
抗生素被用於預防而非治療
必要的資金投入
儘管這個領域急需創新的突破，但全球對抗生素的研究在過去的20年中卻有所下降，為了縮小這日益擴大且危險的議題，百靈佳殷格翰認為投資Aurobac中深耕該領域的Research Beyond Borders團隊，將有機會將研究的差距縮小。此外，百靈佳殷格翰與Boehringer Ingelheim Venture Fund分別向AMR Action Fund捐贈了5000萬歐元，該基金會為一個廣泛聯盟，包含其他製藥公司和機構，以及歐洲投資銀行（見下文）。
Aurobac現在為武器庫增添了強而有力的新武器。
「Aurobac在抗微生物抗藥性的戰役中扮演著非常重要的角色。」Pairet先生表示：「我們的目標是加速在這個領域中整合互補的能力，並加速這個領域的創新研究，使抗生素治療更加高效精準。」
百靈佳殷格翰參與AMR Action Fund的貢獻包含Boehringer Ingelheim Venture Fund
各自投資的5,000萬歐元。
在短期內，每間診所的醫生，可以透過僅在必要時開立抗生素來遏制抗微生物藥物抗藥性（AMR）。而在中長程的目標，醫學界則需要新的治療選擇來防範抗微生物藥物抗藥性，以及新的抗藥性產生。
這正是AMR Action Fund的目標：促進新抗生素的開發，支持從事該領域研究的公司，並在2030年批准2至4種新抗生素。
毫無疑問的，這間基金會具有實現該目標的潛力與實力，首先，它是一個巨大的投資平台，幾家製藥公司和機構，如：歐洲投資銀行，已投入10億歐元以上的資金。其中包括了百靈佳殷格翰與Boehringer Ingelheim Venture Fund分別貢獻的5000萬歐元，同時也是該基金會最大的投資之一。
此外，該基金會也匯聚了許多優秀的公司，結合了學術界與生物技術領域最創新的方法，共同分擔風險與負擔。
Continue research despite financial risks
AMR Action Fund的目的是讓面臨商業風險的企業能持續研究新抗生素。因此，基金會為那些致力開發新抗生素的小型生技與製藥公司，提供了財務支援與專業知識。基金會內經驗豐富的投資者們，也在這方面提供了許多協助，像是尋找新物質，或提供科學建議與管理決策的支援。
近年來，多重抗藥性的數量不斷增加，但新型抗生素的研發卻越來越少，AMR Action Fund為此正積極地為進行這項研究的公司提供支持的方式，彌補新型抗生素的研究差距，目的是恢復科學的平衡，抵抗微生物藥物抗藥性日益加劇的影響。而百靈佳殷格翰與Boehringer Ingelheim Venture Fund將一同參與AMR Action Fund的行動，協助應對這公共衛生的威脅，並造福全世界的人們。
HUMAN PHARMA
Combating a threat to global health security
Humanity is threatened by a dangerous public-health relapse. Infections once considered under control, and even routine surgeries, can once again become life-threatening — all because of bacteria that are becoming increasingly resistant to antibiotics. That’s why Boehringer Ingelheim is helping lead the fight against these “superbugs.”
What doesn’t kill you makes you stronger. It might sound like time-honored truism. But it accurately describes how microscopic bacterial pathogens have been evolving and growing ever more virulent over the past few decades by becoming resistant to antibiotics.
For doctors and patients, it might start innocently enough. A sick person begins a course of antibiotics to fight a bacterial infection but starts feeling better and doesn’t finish the treatment — leaving some particularly resistant bacteria alive. These surviving specimens then have the opportunity to multiply and spread inside the patient before infecting other people. Repeat this process often enough and this particular strain of bacteria will eventually develop a resistance to the antibiotic that was initially used to fight it. The result: a superbug.
Bacteria are developing anti-microbial resistance (AMR) faster than ever before – a situation that the World Health Organization (WHO) is calling a “threat to global health security.” Today, more than 1.2 million people die each year because of AMR, a grim number the UN predicts could exceed 10 million by 2050.
AMR can make complications related to injuries, cuts and common diseases like diabetes far more dangerous. And it has the potential to turn routine procedures like C-sections and hip replacements into life-threatening endeavors.
This mounting threat is why Boehringer Ingelheim is playing a leading role in the global fight against AMR, through partnerships and funding aimed at taking a more precise, science-driven approach to diagnosing and treating bacterial infections.
The contributing causes
There are several reasons AMR has been on the rise – most notably because an estimated 50 percent of people who are being prescribed antibiotics do not necessarily need them. Each dose puts a variety of germs into contact with the antibiotic, which then provides the opportunity to develop resistance.
The trend is also driven by extensive use of broad-spectrum antibiotics in livestock herds. For many years, Boehringer Ingelheim has been dedicated to researching how antibiotics can be administered to livestock in a way which prevents the development of AMR.
Around the world, though, the threat continues. In its 2019 report to the Secretary-General of the United Nations, the Interagency Coordination Group on Antimicrobial Resistance (IACG) called for urgent action against AMR: “There is no time to wait. Unless the world acts urgently, antimicrobial resistance will have a disastrous impact within a generation.”
Toward more precise diagnoses
In June 2022, Boehringer Ingelheim established the joint venture Aurobac Therapeutics SAS, in partnership with leading biotech companies Evotec and bioMérieux, to confront this enormous challenge. The joint venture’s ambitious goal: to develop effective antimicrobial substances to modify treatment regimens, while reducing the risk of anti-microbial resistance.
Too often, under current medical practices, a wide range of infections are treated with broad-spectrum antibiotics, which – as the name suggests – are not aimed at specific bacteria.
“We want to shift the strategy related to antibiotic treatment regimens, which currently lean heavily on empirical approaches using broad-spectrum and unfocused medicines,” says Michel Pairet, Head of Innovation at Boehringer Ingelheim and a Member of the Board of Managing Directors. “The goal is to turn this into a precision approach.”
In practice, the process would begin with a detailed diagnosis and an analysis of the pathogen and its properties. The patient could then be treated with a so-called precision antibiotic, which targets the specific bacteria in question.
“Aurobac has a very important role to play in the fight against AMR.”Michel Pairet
“We employ a modality-agnostic approach that is perfect for developing targeted antibiotics.”Werner Lanthaler
“Our role in the joint venture is to develop and commercialize diagnostic tests.”Alexandre Mérieux
(source)
A powerful team, with complementary expertise
Aurobac’s ambition is no less than a paradigm shift in the use of antibiotics. As the leading investor, Boehringer Ingelheim has provided 30 million euros of the Lyon-based joint venture’s funding of 40 million euros. Evotec and bioMérieux have contributed 5 million euros each. The joint venture provides the three partners with an opportunity to take full advantage of their combined expertise and opens new avenues for research.
bioMérieux has a wealth of expertise in the diagnosis of anti-microbial resistance. The company already provides a range of comprehensive integrated diagnostic solutions that help treatment providers make more targeted use of antibiotics. “Our role in the joint venture is to develop and commercialize diagnostic tests,” says Alexandre Mérieux, Chairman and CEO of bioMérieux. That includes developing “companion diagnostics” which help match patients to specific medicines, Mérieux says.
Evotec, meanwhile, brings to the partnership a leading global platform for combating infectious diseases. With more than 200 researchers investigating novel anti-infectives, the company has extensive expertise and experience in dealing with a wide range of substance classes.
“At Evotec, we employ a modality-agnostic approach for developing precision medicines, including targeted antibiotics,” explains Werner Lanthaler, Evotec’s CEO. “That gives Aurobac the platform it needs to succeed in the fight against anti-microbial resistance through new pathways and substances.”
Why antibiotic resistance develops and spreads
Much-needed investments
Boehringer Ingelheim also sees its investment in Aurobac as an opportunity to close a widening and dangerous research gap. Globally, antibiotics research has actually declined over the past 20 years, despite the urgent need for innovation in the field. Boehringer Ingelheim is combating this trend in various ways.
The company’s Research Beyond Borders team has been active in the field for years. And Boehringer Ingelheim and the Boehringer Ingelheim Venture Fund have each contributed 50 million euros to the AMR Action Fund, a broad-based coalition that includes other pharmaceutical companies and institutions including the European Investment Bank (see below).
Aurobac now adds a powerful new weapon to the arsenal.
“Aurobac has a very important role to play in the fight against AMR,” says Mr. Pairet. “Our aim is to accelerate innovation in the AMR space, bringing together complementary competencies to be able to accelerate innovation in this field and make antimicrobial therapy highly effective and targeted.”
Boehringer Ingelheim’s engagement in the international AMR Action Fund includes a 50-million-euro investment by the company itself and another 50 million euros by the Boehringer Ingelheim Venture Fund.
In the short term, every doctor’s office can play their part in preventing anti-microbial resistance (AMR) by prescribing antibiotics only when they’re needed. Over the medium to long term, however, the medical community needs new treatment options to combat AMR and prevent the development of new resistances.
That’s exactly what the AMR Action Fund is all about – fostering the development of new antibiotics and supporting the companies involved in this research. The fund’s ambitious goal is to see two to four new antibiotics approved by 2030.
Certainly, the fund has the potential and wherewithal to achieve that goal. To begin with, it’s a huge investment vehicle: Several pharma companies and institutions like the European Investment Bank have injected more than a billion euros in the fund. That include Boehringer Ingelheim and the Boehringer Ingelheim Venture Fund, which have contributed 50 million euros each — among the fund’s biggest investments.
Beyond money, though, the fund brings together the best competencies of many companies, tapping into the most creative approaches coming from academia and biotech, while sharing the risks and burdens.
Continue research despite financial risks
The purpose of the AMR Action Fund is to ensure that companies continue to research new antibiotics despite the business risks. It provides financial support and expertise for a range of smaller biotechnology and pharmaceutical companies devoted to developing new antibiotics. The AMR Action Fund’s successful and more experienced investors also have much to offer in this regard – from helping with the search for new substances to providing scientific advice and support with management decisions.
The AMR Action Fund is committed to closing a dangerous gap that has widened further in recent years. The number of multi-resistant bacteria is on the rise while fewer and fewer new antibiotics are being developed. By providing support for companies carrying out this research, the AMR Action Fund intends to restore the scientific balance and counteract the increasing prevalence of resistant microorganisms. Together, Boehringer Ingelheim and the Boehringer Ingelheim Venture Fund are helping the AMR Action Fund confront this public-health threat for the benefit of the world’s people.