In November 2012, at just 18 years old, a high school senior was eagerly anticipating the typical milestones of her final year – receiving college acceptance letters, attending prom, and walking across the stage for commencement. But her life took an unexpected turn when she received a devastating diagnosis: she had been identified with a rare and aggressive form of blood and bone cancer that would rapidly progress and challenge everything she thought she knew about her future.
Littlejohn successfully completed a four-round course of chemotherapy, subsequently entering a state of remission. By June, her cancer had recurred, prompting her to resume treatment. As her immune system weakened due to chemotherapy, Littlejohn was left vulnerable to an infection caused by the bacteria. Despite the fact that the microorganism causing her infection had evolved to resist numerous standard antibiotics that would normally have cured her. Doctors at Littlejohn’s hospital administered the last-resort antibiotic to treat her severe infection, which was resistant to conventional treatments. Despite the use of colistin, the microorganism remained unaffected.
By October, however, the infection had spread to her lungs and then to her bloodstream. One year after her cancer diagnosis, 19-year-old Littlejohn succumbed to complications related to her underlying infection.
Drug-resistant infections such as Littlejohn’s have become increasingly prevalent. Antibiotic resistance arises when microorganisms adapt to survive exposure to antibiotics, a process that can also occur in response to other antimicrobial agents, such as antivirals and antifungals, allowing viruses and fungi to develop immunity to treatment.
Widespread infections have become increasingly resistant and challenging to combat, rendering lifesaving medical procedures such as surgeries, cesarean sections, and chemotherapies significantly more complex.
The World Health Organization (WHO) has identified antimicrobial resistance as one of the most significant global health threats of the 21st century. According to the Centers for Disease Control and Prevention (CDC), approximately 35,000 individuals succumb to drug-resistant infections annually. Globally, the death toll is estimated to be slightly over.
While antimicrobial resistance is an inherent evolutionary process, scientists argue that our rapid and widespread use of antibiotics worldwide is accelerating this phenomenon. Antimicrobial agents are employed not exclusively to combat infections in humans, but also to prevent and control infections in livestock and other animals. When disasters strike countries or regions, the risk of infection surges due to limited access to clean water and inadequate sanitation facilities, exacerbating already dire humanitarian situations. In areas where environmental regulations are lacking, the dumping of pollutants from healthcare facilities and pharmaceutical manufacturers directly into nearby waterways creates a fertile ground for microorganisms to develop resistance.
Multiple factors contributing to the emergence of antimicrobial resistance necessitate a multifaceted approach, encompassing measures such as strengthening infection control protocols and developing insurance policies that incentivize judicious antibiotic prescribing. The urgent need for new antibiotics is starkly evident. Pharmaceutical companies are actively developing new medications, driven by the fact that existing treatments often fail to provide meaningful results. Congress is considering reviving the antibiotic discovery and development process. The Pioneering Antimicrobial Subscriptions to Finish Upsurging Resistance Act, dubbed PASTEUR in honor of Louis Pasteur, has garnered widespread support from lawmakers across the political spectrum as well as numerous public health organizations. Despite this, concerns persist that the proposed act could inadvertently restrict access to desperately needed antibiotics globally, further exacerbating existing global health inequalities?
The pharmaceutical industry began developing antibiotics. Currently, a limited number of companies are enthusiastic about establishing fresh entities. Major American and European pharmaceutical companies possess robust antibiotic discovery portfolios, while numerous smaller organizations are actively pursuing the development of antimicrobial agents. Despite significant advances since 2017, the US Food and Drug Administration and its European counterpart have only approved a handful of new antibiotics, with 10 of those approvals mirroring existing medications against which pathogens had already developed resistance.
Pharmaceutical companies are hesitant to develop new antibiotics because the financial model for drug development does not deem them profitable, according to experts. Companies occasionally invest substantial sums in research and development of novel medications, including the costly expenses associated with large-scale clinical trials necessary for regulatory clearance from the Food and Drug Administration (FDA). Companies recover this investment when a successful medication is launched and starts generating revenue from sales to patients and consumers. The profitability of a drug hinges on its price, demand from patients, treatment duration, and dosage requirements.
The challenge surrounding antibiotic use lies in their affordability and lack of consistent application among the general public.
While individuals and animals worldwide remain susceptible to infectious diseases, episodes of infection occur sporadically, often requiring antibiotic treatment over several weeks to combat the illness – albeit, this approach can backfire if the infection becomes resistant to these medications. The restricted remedy interval constrains the amount of antibiotic sales, resulting in insufficient revenue for corporations to justify investment in antibiotic development, as lamented by the CEO of a leading pharmaceutical company specializing in antibiotics?
The proposed solution to hike antibiotic prices to thousands of dollars per dose may not resonate well with the public and medical insurance companies, given the average cost without insurance is already in the range of several hundred dollars. In many European countries, national governments determine the value of medications.
To combat the urgent threat of antimicrobial resistance, various governments are actively developing innovative strategies to stimulate and drive antimicrobial research and development. The Pasteur Act refers to a specific legislative initiative aimed at promoting public health and medical research. Last year, the US Senate re-proposed a bill following an attempt that didn’t pass in 2021. The revised Pasteur Act model is significantly underfunded, with a cap of $6 billion compared to the original allocation of $11 billion.
The proposed Pasteur Act would facilitate the US government’s ability to negotiate subscription-like agreements with companies that produce antibiotics, allowing for more streamlined and efficient production of these critical medications. The US government offers substantial incentives to pharmaceutical companies, committing up to $3 billion over five years as soon as an antibiotic receives FDA approval, to ensure continued production of the life-saving medication, according to Dr. [Last Name], chief of analysis and growth at a leading nonprofit dedicated to fostering antimicrobial innovation? The US authorities would subsequently offer the antibiotic at no charge to federal medical insurance beneficiaries, including veterans and seniors enrolled in Medicare. The revised language stipulates that the Division of Health and Human Services must further incentivize private medical insurance providers to establish subscription-like agreements with pharmaceutical companies to secure antibiotic supplies, which will be funded through the act.
“Duffy argues that your approach to decoupling sales from quantity metrics is flawed.”
Currently, the US authorities provide funding for early-stage drug development and growth, while various non-governmental organizations (NGOs) fill the gap by supporting promising candidates nearing final-stage medical trials. While the Pasteur Act ensures funding for selected antibiotics at a critical juncture in their development – immediately following FDA approval?
During the post-approval period, experts confirm that a medication has been proven to be both effective and safe. While significant barriers remain, numerous costly challenges must be overcome to secure widespread pharmacy distribution. Pharmaceutical companies are mandated by law to conduct clinical trials involving children within five years of receiving FDA approval. The proposed development could potentially cost upwards of $80 million, consistent with Cirz’s estimates. “So that could potentially bankrupt you overnight,” he warned.
Scaling up manufacturing capacity to meet increased demand comes at a significant cost. During pharmaceutical clinical trials, companies manufacture medication at a designated research facility. Upon receiving FDA approval, organizations should seamlessly transition their production to larger-scale industrial facilities. According to Cirz, the cost of this endeavour is estimated to exceed $100 million. Intravenous administration is often required for newly developed antibiotics targeting severe infections, necessitating their packaging in sterile vials – an added costly burden.
The Pasteur Act aims to provide timely and sustainable funding for its crucial five-year period. According to Cirz, the company is struggling to maintain a stable financial footing due to insufficient revenue, stating that it cannot generate enough income to meet its payment obligations. While pharmaceutical companies do develop and market antibiotics, their profit margins may not be comparable to those from blockbuster drugs like treatments for rheumatoid arthritis, which generated significant revenue in 2022. The $750 million to $3 billion influx of capital can enable corporations to recover their investment through analysis and growth, potentially allocating resources towards the development of alternative antibiotics, according to Duffy.
While the bill enjoys broad support from both parties in Congress and various well-being organizations backing its passage, some healthcare stakeholders, such as Doctors Without Borders, have expressed reservations about the legislation’s approach. Experts caution that antibiotics engineered under this paradigm may be costlier and less accessible in developing countries where the burden of antimicrobial resistance is more pronounced, exacerbating existing disparities in healthcare outcomes.
The Pasteur Act is poised to alleviate significant challenges facing US pharmaceutical companies, its intended purpose. Despite these efforts, antimicrobial resistance remains a pressing global challenge. The rapid spread and development of antibiotic-resistant bacteria worldwide poses a significant threat to global health. Subsequently, several prominent health organizations have criticized the proposed legislation for neglecting the far-reaching global implications of such regulations.
Several developed economies with well-established pharmaceutical sectors, including Germany, Japan, and the UK, have either implemented or are exploring their own initiatives to foster antibiotic development? The Pasteur Act dwarfs these. Will likely prompt a surge of pharmaceutical companies to focus on producing essential medications for the US market, potentially neglecting other regions’ needs.
“The magnitude of the Pasteur Act’s scope is expected to be so substantial that it ultimately prompts builders to focus exclusively on the US market, solely producing the drug for proper use in the US and registering it in the US, as this will likely generate sufficient revenue and incentives, making what would otherwise be a relatively unprofitable market worthwhile.”
As the steady influx of Pasteur Act funds continues, pharmaceutical companies may become increasingly reluctant to invest additional resources into developing methods to manufacture their antibiotics at a lower cost. When revenue margins are capped by regulatory authorities, corporations tend to prioritize investing in ways that boost their profitability rather than reducing manufacturing costs, as there is little motivation to decrease prices and potentially divert attention towards developing new medications. Without this innovation in low-cost manufacturing, the proposed legislation risks inadvertently preventing countries like India from being able to produce the medication independently.
While individuals with federal medical insurance plans can be guaranteed access to antimicrobials that benefit from the act, there is no provision or guidance in the proposed legislation to ensure global access to these medicines. Pharmaceutical corporations would retain autonomy in setting prices, production, and distribution strategies for antibiotics under this funding model, according to Ava Alkon, global health policy and advocacy advisor at Doctors Without Borders?
“A key omission, according to Alkon, is that the act fails to establish meaningful pathways for individuals outside of existing federal programs or, indeed, outside the United States, to gain affordable access.”
“After decades of experience at various entry points globally, we’ve often seen a pattern emerge: valuable resources are typically auctioned off to the highest bidder, rendering them inaccessible in numerous contexts where they’re most needed.”
The origins of prioritizing distribution lie deep in a troubled history of unequal access to antibiotics. Between 1999 and 2014, a mere 21 new antibiotics were developed. Primarily listed are international brands that have secured registrations in over 10 countries, with a majority being located in high-income nations situated in the northern hemisphere.
Despite appearances, a subtle tension exists beneath the surface. The widespread misuse of antibiotics has been identified as a primary driver of antimicrobial resistance, prompting several countries to take measures to restrict their use – for instance, by limiting the availability of antibiotics on the market. This approach could help preserve the efficacy of newly developed antibiotics and those that benefit from the Pasteur Act’s provisions. Does the passage suggest that lawmakers are morally obligated to intervene in global health crises?
If the Pasteur Act aimed to ensure global access to new antibiotics, a committee established under this act could amplify worldwide concerns by, for instance, mandating that pharmaceutical companies license their medicines in developing countries, as recommended by GARDP. While the committee may allocate some funds to combat antibiotic-resistant infections prevalent in low-income countries, which are unlikely to impact the US directly?
While the Pasteur Act may not fully address the complex issues surrounding antibiotic development and antimicrobial resistance, it marks a significant step forward in tackling the pressing public health concerns of our era.
“There’s little doubt that this project will enable me to become economically profitable as a drug developer,” Cirz stated. “Does it repair the system? I fear that it may not work, and I fear that it will introduce fresh problems instead. Yet, at this stage, every individual is resolute that a singular event unfold.
