We are living in a period of great paradoxes, from a scientific medical point of view. A historical moment in which pure research is proceeding at an exponential rate, to the point of hinting at epochal revolutions in the treatment of diseases. Counterbalancing this scenario is the other side of the coin: a problem with the sustainability of the costs of therapies, the difficulties in accessing them due to bureaucracy, inadequate regulations (for current times), and bottlenecks on the part of regulatory bodies, caused by a demand for approvals that has found governance apparatuses unprepared for this acceleration.
In practice, oversimplifying greatly, but not wrong regardless, it is as if the world of healthcare is proceeding at two speeds: on the one hand-through the “omics” revolution-openings are being opened for treatments that were previously unimaginable.
On the other hand, the numerical lack of resources and expertise risks not thwarting but certainly slowing access to therapies. And so the journey from research labs to the patient’s bedside turns out to be far less linear than it should be and than we can imagine.
The research boost
If we look at the situation in its complexity, we cannot ascribe this tortuous journey to a single specific cause. If that were the case, the problem would be easily solved. Instead, it is a composite scenario. Let us start then, on this imaginary journey from the laboratory to the patient’s bedside, with research. Worldwide, some 4,565 trials referring to advanced therapies are currently in the registration phase.
Of these, as many as 112 are in phase 3 trials. Making a quick excursus on the Italian reality (which has its specificities), we can say that the situation has its own vivacity, made of numbers that are not indifferent: among the first advanced therapies approved by Ema, four were developed in our country.
Data from 2022 indicated how there were 23 clinical trials underway to meet unmet clinical needs, essentially in the fields of oncology, rare diseases, and neurodegenerative diseases. While these numbers testify to the vitality of the research and industry ecosystem (of the 112 phase three studies, 99 are being conducted in the biopharmaceutical industry, 13 by the academic/governmental or otherwise institutional sector), we need to understand the equal and opposite forces that make the availability of drugs on the market similar to Odysseus’ landing in Ithaca after the Trojan War.
At a high price
One of the first problems is undoubtedly that of cost. Because innovative therapies work and also very well, but they have the “defect” of being extremely expensive and not only that: at present, many of them intercept the needs of patients struggling with rare diseases, because they are extraordinarily well characterized from a biological point of view and, therefore, it is easier to identify a therapeutic target. Spending on these therapies is increasing exponentially (as a consequence of the increase in the number of approvals).
In 2023, spending was less than 300 million euros. But projections show how as early as 2027 the range is between the cheapest forecast, which still brings costs to 905 million, and an increase to 1.810 billion.
The cause of this cost explosion has to be sought in the expected approval of new therapies; if the development and approval trend continues according to projections, by 2030 we could have up to 60 new cellular gene therapies in the medical arsenal, with the plateau of patients eligible for treatment widening to 350,000.
The question, then, is this: how will resources be recovered to make these therapeutic pathways accessible to all and sustainable? If we listen to the clinicians, we have to introduce some important variables into our reasoning, which are those related to social costs (lost work hours, progression to disability, expenses to be incurred anyway for other therapies that are still necessary, increased hospitalizations due to worse disease control) and indirect costs.
And the reasoning is undeniably true. Recently (just to give one example), finerenone was approved as a molecule to control the progression of renal tissue damage in chronic renal failure. Potentially, the drug reduces the progression to dialysis, and each dialysis patient costs the SSN between 30 and 50 thousand euros per year, to be multiplied by 50 thousand, that is, the number of dialysis patients.
The role of regulatory agencies
However, no one can predict with certainty which and how many patients with kidney failure is certainly destined for dialysis and, therefore, the criteria for the reimbursability of finerenone have been overall restrictive and dedicated to the categories of patients most at risk. Somewhat like what happened with the first antiviral therapies against hepatitis C, initially (because of the high costs at the time) dedicated only to those who showed unequivocal signs of disease progression.
Expensive therapies mean great financial commitment for the health care system, and, therefore, one has to contend with blankets that risk being too short, especially at a time when resources allocated to health care are subject to substantial contraction anyway, given the need to balance the state’s books.
Here then, the situation becomes more slippery when we know that Aifa actually is active in approving innovative therapies. In the period between 2018 and 2021, just to give a practical example, Ema had approved 46 innovative therapies in oncology. Aifa, of these 46, approved as many as 38. This was an extraordinarily flattering achievement because it put our country in second place after Germany and Switzerland.
One might therefore think of a major effort to allow access to the best standards of care assured by scientific medical progress, but this is not exactly the case. Aifa, in fact, certified the goodness of the approach but the cost-benefit study took an average of 419 days to get the therapy to the patient’s bedside. Clearly, a 419-day wait can make all the difference in the world when it comes to oncological diseases. And it is a wait that becomes even less understandable when we learn that regulators in other nations manage to make similar assessments in half the time. Often even less.
Tools such as Early access by Aifa are not, at present, sufficient to meet the demand for advanced therapies. According to an Aiom survey, 90 percent of oncologists have sought advanced cancer drugs through this tool. It is clear that clinicians are well aware of the benefits of such therapies for patients. And so seeking to give them full availability is an ambition that makes them shy away from any wait-and-see.
After all, precisely the wait-and-see attitude regarding innovation in health care is an atavistic flaw. Just think of health care digitization: in the pre-Covid era, in the face of substantial approval of the intent, the legislature required that the reorganization of the system be done with economic invariance. Reform could be done and was desired by all. But since there was no money to make a system investment, it was necessary to wait for the pandemic, first, and the NRP funds, then.
