The Moral Economics Of Precision Medicine

By Kat Kozyrytska and Ryan Murray

Precision medicine is no longer a futuristic promise. It is here. It is reshaping drug development. It's changing what patients should expect from healthcare. But, as with every breakthrough in science, the story is more complicated beneath the surface, particularly when colliding with market forces.

We inherited a paradigm where breakthroughs are swiftly backed by investors with the expectation of blockbuster returns. With the dawn of cell and gene therapies, among other precision modalities, the expectation was that these too would fall in line, but they have not. Unlike past breakthroughs, these novel and promising therapies are burdened by realities of cost and scale (and return on investment) that are orders of magnitude more difficult to fit into the traditional blockbuster model.

The Rise Of Personalized Precision Medicine

More than 25% of FDA approvals since 2015 are labeled as precision medicines, which is to say they are associated with a biomarker (currently, mostly NGS-based). A 2016 meta-analysis of NCI-MATCH trials showed that precision medicines are six times more likely to be efficacious compared with traditional medicines. Drug discovery has been increasingly focused on specific mutations, molecular profiling, and increasingly specific patient subsegments. With precision medicine, the concept of “average patient” is losing its value in the drug development conversation. Yet, paradoxically, commercial discussions in working groups still highlights achieving “blockbuster status,” a phrase typically applied to therapies that can serve millions of patients.

Given all of this, why do we still talk about blockbuster drugs? This is especially perplexing for cell therapies, which are arguably some of the most tailor-made therapies developed in the history of medicine. The answer of course is straightforward: return on investment. Cell therapy developers need to fundraise, and they would like to show a “hockey stick” curve of returns – steep, rapid, exponential returns, just like everyone else.

While the impact of personalization of therapies is highly beneficial for the patient, it may take the same — or greater — amount of capital to develop a personalized curative therapy as a blockbuster daily pill, weekly injection, or monthly infusion. Meanwhile, the returns of a personalized therapy follow sophisticated, moral math, involving an equation that encompasses patient benefit rather than pure dollars.

The Human Cost Of Trial And Error Medicine

The very fact that it is normalized for a patient to go through a number of medicines is fundamentally questionable from the perspective of ethics. For patients with immediately life-threatening conditions, such as cancer, going through multiple lines of therapy may jeopardize their survival. A study from 2001 (p.6 in this report) suggests that within the cancer drug class, medications are ineffective for 75% of the population. We have to hope things have improved since, but more recent similar studies have focused on drug metabolism, adverse drug reactions, and adverse gene-drug interactions.

If patients can’t get a therapy efficacious for them right away, they may not survive long enough to see effective treatment. For patients with autoimmune indications, it is the quality of life, their ability to have — and hold on to — jobs (and health insurance), and thus their livelihood that is compromised. When it comes to the even less understood field of mental health, such as bipolar disorder, patients report going through three to 30 different medications over the course of 10 years before getting to the right one, which is considered typical. Let the years of life and lost productivity sink in.

The Reality For Developers, Clinicians, And Investors

Of course, the field is well aware of these issues. Of course, we have clinicians who are deeply, fundamentally committed to their patients’ benefits. And of course, we have therapy developers who are committed to finding lifesaving treatments and cures. However, they are pressured to deliver a hockey stick of returns.

Let’s consider the blockbuster GLP-1s. It is clear through the expanding set of trials that now include addiction, depression, and more, that the exact mechanism of action of GLP-1 agonists is not fully understood. For example, reports of weight loss through decreased appetite stemming from downregulation of pleasure circuits (the same mechanism likely at play with GLP-1 agonists’ potential effects in addiction) suggest broad-spectrum effects across a variety of systems. 

It’s not hard to imagine a next generation of GLP-1 agonists that are more targeted, biomarker-associated, and tailored to the individual. This would amount to turning today’s broadly acting drugs into, yes, a precision medicine.

For cell therapies, figuring out how to position the precision medicine approach with investors is essential. Therese Choquette of Tigen Pharma believes that we will see increasing pressure from regulators and efforts by the industry to better define patient biomarkers for cell therapies. Whether these biomarkers will be predictive of efficacy or manufacturability, they will likely further define the subset of patients eligible for a given cell therapy. These patients are more likely to see better results, while those who are not eligible will skip this line of therapy and go straight to a therapy that has the higher likelihood of healing/curing them. Great for ethics. Tough for an investor pitch.

The Healthcare Paradox

So here we are, faced with the age-old dilemma of ROI vs. ethics.

To quote Rob Tressler of Excellos, “we are in healthcare, not moneycare.” This points to a potential fundamental difference in the nature of investments in healthcare vs. other fields.

• Should we consider implementing sophisticated, moral math for healthcare investments that takes into account both financial returns and benefit to humanity? How can we account for ethics in the ROI?
• Are there paths we can envision in addition to performance-based reimbursement?

At the end of the day, the challenge in these promising novel therapies is balancing the undeniable value to patients with the equally undeniable need for sustainable investment. The science is there, the clinicians are committed, and the patients are waiting. What remains is the collective responsibility of developers, investors, regulators, and policymakers to rethink the math of ROI in healthcare as a blended equation where human benefit and financial sustainability can coexist. This is easier said than done, but if we get this balance right, the reward will be measured not only in market returns but in exponentially more lives changed. That is the kind of hockey stick curve worth chasing.

About The Authors:

Kat Kozyrytska is an industry consultant who works across the ecosystem of regulators, therapy developers, and technology companies to evaluate, implement, and de-risk artificial intelligence. She holds an S.B. in biology from MIT and an M.Sc. in neuroscience from Stanford University.

Ryan Murray is a quality and manufacturing science senior consultant with ValSource Inc. where he focuses on facility design and control, technology transfer, process qualification, and aseptic risk management in biologics and advanced therapies. He has a B.S. in biomedical science and an M.S. in biochemistry and biophysics from Texas A&M University.