In 1962, President John F. Kennedy stood in Houston and challenged the nation to undertake bold and drastic technological advancement to achieve the goal of reaching the moon. The speech he gave that day was considered the original moonshot address.
We use the term “original” because the spirit it encapsulated has been drawn from repeatedly through the decades for setting the stage in various attempts at human milestones. Not only was Kennedy’s original challenge met, but the endeavor laid the foundation and assuredness for future scientific progress in the United States.
Perhaps the most amazing accomplishment was not actually landing on another celestial body for the first time, but rather the creation of a collective willpower with the coordination of large groups of people pursuing and executing many smaller objectives that eventually paved the way toward that ultimate of historic achievements.
Drawing inspiration from this moment in American history, another moonshot, this time in the realm of cancer medicine, was first announced in 2016 and more recently refined. The challenge to the scientific medical community and our society at large is to eradicate death rates from cancer by 50% over the next quarter century.
A multifaceted approach will have to be employed for such a major undertaking, not only focusing on the development of novel treatment strategies in the future, but also for cancer prevention. The plan is made possible by generous funding from both private- and taxpayer-funded sources.
Due to its aspirational nature in attempting to comprehensively address a scourge amongst humanity, the great excitement amongst the scientific community and society at large around the Cancer Moonshot is justified.
Troubleshooting lessons from the Apollo moon program could actually provide wisdom for us in today’s Cancer Moonshot Initiative. During the developmental testing of the massive F1 engines that powered the Saturn V launch vehicle towards low Earth orbit, the engines would continuously explode.
The engineers knew that without these engines there would be no shot at the moon, without addressing the ABCs there would be no grand novel. To accomplish their goal, they had to fix this steppingstone of a problem.
We use this example as analogy, because today we too are facing a basic and vexing problem that if not urgently addressed really undermines the spirit of the Cancer Moonshot.
Our problem today is the inability in our country to consistently provide inexpensive, curative cancer therapeutics that exist not at some time in the future, but right now.
This present shortcoming is manifested in the form of significant and growing drug shortages, despite having the most technologically-advanced medical system in the world.
The United States is by no means a stranger to critical drug shortages. Given the connectivity of the global supply chain some of this can be expected. However, these shortages are becoming more frequent and damaging to patients.
At the end of 2022, close to 300 drugs considered “critical” were on national shortage, a 30% increase over the previous year. The frustration surrounding this is magnified when put in the context of a child or adult who has a cancer diagnosis and is unable to receive standard and lifesaving care.
Oncologists are then forced to choose from a menu of suboptimal alternatives, which themselves become scarcer as their demand collaterally increases, eventually leading to no effective means to treat.
The issue then evolves from one of logistical inconvenience to one of moral dilemma, including rationing of life-saving inexpensive drugs. We must reconcile our declaration to eradicate cancer in the future while not doing everything we can to eradicate cancer in our current patients.
The measure of success is not whether you have a tough problem to deal with, but whether it is the same problem you had last year.
John Foster Dulles
As this scenario expands to more lifesaving medicines, it has thankfully garnered further attention from the United States government. Hopefully, government involvement may prevent this worsening situation from joining the annals as another “new normal” of modern society.
In 2019, Sen. Gary Peters (D-MI) and the Department of Homeland Security released an executive summary which addressed this question by outlining the conditions of drug prices, shortages and the potential points for intervention. With some time to address the issue post pandemic, in March 2023 congressional hearings were held resulting in a Majority Staff report which focused on the details.
In brief, for many lifesaving drugs, the active pharmaceutical ingredient (API) is manufactured outside the United States. This is particularly common for generic injectable inexpensive drugs.
Instead, we rely significantly on foreign sources leaving us completely vulnerable to any disruptions in foreign supply chains which cannot be fully regulated. At this time, an eye opening 80 to 90% of APIs are created outside the United States, and this is true for up to 95% of generic sterile injectable drugs assigned for critical care.
This reality is based on economic considerations, as there is little incentive for a company to produce generic drugs which do not generate a profit, resulting in a shift in drug manufacturing overseas to some of our geopolitical rivals.
Governments, including India, China and others are willing to offer tax breaks, less regulatory oversight, cheaper labor forces, and other subsidies making them a more attractive option for profit-driven operations.
Simply put, it comes down to money, and when one considers that the United States would not be able to efficiently manufacture life-saving medication if we were in a pinch, this should invoke in all of us some degree of embarrassment and alarm, even as we tout our technological advancements in the field of medicine—and especially cancer care—on a daily basis.
This does not just affect inexpensive curative chemotherapy agents, but also antibiotics necessary for management of patients receiving high doses of curative agents (e.g., for acute leukemia).
One poster child amongst many exposing the pitfalls of this outmoded drug production system is the lifesaving chemotherapy drug cisplatin.
This simple salt, first described in 1844, is used in the treatment of many malignancies, including germ cell tumors, bladder cancer, and gynecologic malignancies, ovarian cancer among them. For young men with testicular cancer, it forms the basis for a regimen that offers more than a 90% cure rate.
The drug most recently went on shortage in March 2023, and as of April 2023 cisplatin, as well as carboplatin (indicated for multiple solid tumors) are both on shortage. This is expected to last for several months, if not longer, as described by the Society for Gynecologic Oncology.
Another drug in extreme shortage since last year is fludarabine, the optimal backbone for chemotherapy regimens for patients receiving allogeneic stem cell transplantation and state of the art cellular therapies such as CAR T cells, NK cells and TILs for lymphoma, multiple myeloma, leukemia, and resistant solid tumors. The workaround has required either a potentially inferior alternative or foregoing potentially curative investigational therapies.
Solutions
Using recently passed legislation such as the CARES Act (2020), the American Rescue Plan (2021) and the Consolidated Appropriations Act (2023) the federal report mentions that government agencies are investing more in local drug manufacturing.
After 2020, the FDA also created and updated an Essential Medicines list because of an executive order. There are new non-profit generic drug manufacturers such as Civica Rx who are helping to bolster the national production of some essential drugs across multiple categories including chemotherapy.
The efforts are a first step, and the agencies themselves recognize they are not enough and offer only a bridge to some future unknown solution. For example, currently cyclophosphamide is the only chemotherapy drug on the FDA’s Essential Medicines list.
Our major obligation is not to mistake slogans for solutions.
Edward R. Murrow
Philosophically and morally, we as a country must decide if inefficiencies in the systems of production are a viable excuse for the avoidable loss of human life. Does this align with our stated desire to significantly eradicate cancer deaths?
We know what we should say.
Historically, we have prioritized an efficiently functioning economy and have shown that if we think something is important, we can muster the collective will to invent a better solution.
This spirit was demonstrated by the creation and implementation of the Strategic Petroleum Reserve (SPR) which is the world’s largest supply of emergency crude oil created by the Energy Policy and Conservation Act (EPCA) on Dec. 22, 1975.
Its stated purpose is to “reduce the impact of disruptions in supplies of petroleum products and to be a significant deterrent to oil import cutoffs” for whatever reason they may occur. The context in which the reserve was set up sounds eerily familiar to the environment in which we find ourselves today around drug shortages.
The “essential” in the FDA Essential Medicines list is defined as products that are “most needed for patients in US acute care medical facilities, for short-term treatment of severe injuries, illnesses, and urgent medical conditions.”
However, this definition excludes medicines for longer-term chronic management, including those needed to cure a condition through weeks or months of treatment. In the setting of expanding chemotherapy shortages, we believe this must be changed.
If we can prioritize protecting our economy, we are stating we should have no problem prioritizing the value of human lives by saving them today when possible.
The question is when it comes to cancer care, as we await a more feasible long-term solution, what can be done immediately? The incremental positive steps mentioned in the government report will take time to fully implement and realize, and still will not mind all the gaps.
What is lacking is a safety net that fortifies and strengthens approaches such as future domestic production. Resiliency and consistency are the necessary foundations for a long-term solution, such that when a future shortfall of a lifesaving chemotherapy drug occurs (i.e., due to increased demand or a supply chain shock), the United States would have the means to mitigate the fallout by offering as close to an uninterrupted supply of certain drugs as possible. This could be estimated based on yearly utilization of the drug.
We think these principles could be realized by proposing a federally overseen Strategic Reserve of Essential Medicines (SREM) akin to the SPR, perhaps developed and maintained by the National Institutes of Health or Center for Disease Control and Prevention.
An adequate supply of medications including inexpensive and lifesaving chemotherapy can be manufactured (under government contract) and stockpiled, to be released in the event of global and domestic supply chain disruptions.
The Executive Order that created the FDA Essential Medicines list allows agencies to “focus efforts to mobilize domestic production, accelerate FDA approval and clearance of domestically produced medicines and countermeasures, and it may also prioritize contracts to vendors for efficient domestic production.”
The idea, however, of stockpiling these medications including those which could save the lives of children and adults with various cancer diagnoses has, to our knowledge, not previously been floated.
Once again, these are medications which have been in use for decades and are inexpensive, therefore the approval and clearance process could have already been taken care of ahead of time.
A starting list of reserved chemotherapeutic agents would include: cytarabine, carboplatin cisplatin, cyclophosphamide, methotrexate, paclitaxel, fludarabine, vincristine, and doxorubicin.
This will require a significant collective will from legislators, as well as a push from constituents and patient advocacy groups. The attempt is well worth it and would start to uncouple government dependence on the private sector.
When one considers that the United States would not be able to efficiently manufacture life-saving medication if we were in a pinch, this should invoke in all of us some degree of embarrassment and alarm.
Satyajit Kosuri
Refinement of the logistics would be required and expected as with any endeavor. Patients having to fight a cancer diagnosis is difficult enough and adding to it the turmoil of not knowing if curative therapy is available because of issues in production is not an option our society can accept any longer. If we plan on living up to our own moral standards and the goals of the Cancer Moonshot Initiative, the urgency of bringing into reality a novel idea such as the SREM cannot be overstated.
One could argue that this type of effort could be a foundation of the Cancer Moonshot initiative, as success here would demonstrate we are dedicated to all cancer care and not just that care that generates profits for domestic and foreign corporations.
