Healthcare in 2023: a Little Further Down the Road

Back in 2021, I wrote a very personal article, drawing on a painful experience to reflect on the state of healthcare. It was an article primarily born out of disappointment and frustration, but with a small optimistic undertone, driven by a belief (or a desire) that technology would eventually get us closer to our goal of perfect healthcare. I followed up that article with another one, where I reflected in more depth on what contributions I could personally make - however small - to advance us along that road towards perfect healthcare.

Now, approximately two (very eventful) years later, I thought it was time to reflect on how far we have come since.

The rise of mRNA vaccines for disease prevention and treatment

During the pandemic, mRNA vaccines - most notably Pfizer/BioNTech's Comirnaty and Moderna's Spikevax - were making the front pages of newspapers around the world. Their success and (relatively) rapid development turned the spotlight on the potential use of messenger RNA-based therapeutics beyond the prevention / reduction in severity of infectious diseases, and this space has been heating up in the past couple of years.

As this article from December 2022 highlights, potential applications are vast, due to a number of significant advantages over more conventional approaches: their relative cost-effectiveness, their relative manufacturing simplicity, their speed of development, and their ability to target pathways previously thought of as undruggable.

An interesting side-note: despite all the media attention on COVID-19 vaccines in the past few years, the average consumer doesn't really seem to care too much about the technology used. As data from the consumer arm of the Ipsos Global Syndicated Vaccines Study indicates, "vaccine technology / approach used" ranks significantly below metrics such "company reputation" and "effectiveness against new variants" as a reason for preferring Pfizer/BioNTech's or Moderna's vaccines, in the majority of markets [1].

With regards to the potential application of mRNA therapeutics in other disease areas, a few categories stand out in particular:

• Cancer: various approaches are being studied, most notably using personalised mRNA vaccines to target neoantigens present in each patient's tumour, in cancer types such as melanoma and colorectal cancer
• Cardiovascular: examples include the potential application of mRNA therapeutics for myocardial ischemia, heart failure, arrhythmias, hypercholesterolemia, and arterial occlusive diseases

Additional areas under investigation include haemophilia, renal diseases, and many others.

Could mRNA therapeutics prove to be curative in diseases that are not commonly thought of as being curable, such as metastatic cancer? This remains to be seen. Results from trials so far are encouraging, but it is too early to tell whether the prolonged remission rates seen in those trials point towards the potential of complete tumour elimination. The prospect of potentially turning metastatic cancer into more of a chronic disease - if not outright curing it - certainly seems closer than before.

Gene therapies

mRNA therapies are sometimes thought of as gene therapies, but this is an incorrect assumption. Indeed, concerns about mRNA vaccines somehow altering our DNA are unfounded, and while the confusion is perhaps understandable, they are two very different concepts entirely.

Whereas mRNA therapeutics deliver messenger RNA to cells and then use the cellular machinery to translate that RNA into proteins, gene therapies are designed to alter DNA (usually in our somatic cells) directly, in a variety of ways.

Gene therapies aren't exactly a novel concept; they've been talked about since the 70s, and I remember lots of anticipation during my molecular cell biology and genetics lectures back in the late 90s/early 00s. The first gene therapy to be approved was Gendicine, approved twenty years ago (in 2003) in China (from where I am writing this article), for the treatment of head and neck cancer.

Despite a few more product approvals between 2003 and 2020 (including by the FDA and the EMA), it is only recently that this field has started gaining significant momentum, with the number of gene therapies in development and nearing potential commercialisation increasing exponentially. As of October 2022, there were over 2,000 gene therapies in the pipeline. Areas where gene therapies hold particular promise include primarily rare diseases, such as haemophilia, rare skin disorders, Huntington disease, ATTR, Duchenne muscular distrophy, other rare nervous system disorders, and inherited retinal diseases.

While they have the potential to be curative for patients that otherwise would have to deal with debilitating lifelong conditions, not all physicians are currently unreservedly enthusiastic about their potential [2].

Despite their reservations - which are perhaps understandable given the lack of long-term safety and efficacy data for most of these products - I personally believe that gene therapies represent a major step on the road towards perfect healthcare... provided access is ensured for all who need them.

Equity in access

This point cannot be stated often enough: what good are amazing medical advances when they remain out of reach for significant subsets of patients, due to their nationality, their income, or even their gender? I've written numerous posts and articles on the subject, such as a POV on a comparative lack of access to targeted therapies for cancer among less affluent patients in China, and notably lower testing rates for important cancer biomarkers among poorer patients in the Philippines [3]. The latter point in particular - inequity in access to biomarker testing - is a topic that isn't discussed widely enough, and I am planning to explore this in much greater detail in the coming months.

Sadly, I fear these inequities are going to become even more pronounced as the therapeutics discussed above become more prevalent. While mass-produced prophylactic mRNA vaccines aren't particularly expensive (though more costly per dose than more traditional vaccine approaches), personalised therapeutic mRNA vaccines are likely to come with a significant price tag (especially if they are combined with other immuno-oncology drugs, as they are in most ongoing cancer trials). The logistics involved also mean that there might be significant barriers to access in rural areas.

Gene therapies, meanwhile, are a in a league of their own when it comes to cost. As per this paper from the World Economic Forum, low and middle income countries are less likely to benefit from gene therapies due to their very high cost, and more must be done to ensure and accelerate equal access across the globe.

Artificial Intelligence

Given that it's barely possible to write an article on any topic without referencing AI these days, I figured no article on the future of medicine could possibly be taken seriously without at least a mention of it. There are plenty of thought pieces out there by experts who are far more knowledgeable in this field than myself, so I will keep it simple: AI is set to transform drug development (including that of personalised mRNA therapeutics and gene therapies), clinical trial design, clinical decision-making, and more. It goes without saying that this field is also fraught with risks and controversies, and that - for all its promise of democratising healthcare - it could conceivably lead to further rifts in access between those who are able to benefit from advanced technologies, and those who are prevented from doing so.

Preventative care & early diagnosis

The advent of novel drugs, such as gene therapies and mRNA therapeutics, represents great progress for those suffering from a range of diseases, but it is also worthwhile to take a step back and consider if more can't be done to prevent those diseases in the first place. In the case of gene therapies, this is arguably a bit of a misleading question, as many of the conditions that they are designed to treat are by definition inherited conditions. Putting those aside for a minute, it is undeniable that the impact of many of the world's major healthcare problems could be reduced through lifestyle interventions and educational campaigns aimed at disease prevention.

There are both positive and negative stories to be told regarding our progress in this space. To start with a positive example, smoking rates continue to decline in many countries around the world, and this is clearly correlated with a drop in lung cancer mortality. On the other hand, publications such as this recent paper that shows obesity, hypertension and diabetes rates continuing to increase among young adults in the US are certainly not a cause for celebration. The fact that there is a clear link here with social determinants as well, and that hence there is inequity in disease prevention as well as inequity in treatment access, is well-known. Clearly, much remains to be done to address these issues.

A related topic is that of early detection: the earlier a progressive disease such as cancer is diagnosed, the better the prognosis generally is due to being able to treat/cure the disease before it has progressed too far. Again, this is not a novel concept: breast cancer, prostate cancer and colorectal cancer screening programmes have been around for decades (though they are not without their controversies). What is, however, a much more recent development is the advent of blood-based multi-cancer early detection (MCED) tests. Being able to detect cancer early through a simple blood draw, rather than having to go through more invasive, risky or potentially painful screening procedures, could potentially save lives by reducing the threshold to getting screened. Furthermore, there are some indications that these tests may have a lower false-positive rate than traditional screening methods. Last but not least, these tests are potentially able to detect cancer types early for which no reliable screening methods exist.

One last topic I'd like to mention under this heading: the emerging field of anti-ageing medicine. The incidence of many diseases increases dramatically as people get older, and it is becoming increasingly clear that biological age - as opposed to simple chronological age - is the key driving factor of age-related diseases. If we can halt or even turn back the biological clock through a combination of targeted interventions, allowing people to increase not just their lifespan but - most importantly - their healthspan, it should help decrease the incidence of many ailments that are currently common in old age. Reversing the biological clock may turn out to be one of the best strategies in preventative medicine, giving people access to not just more time, but more healthy years.

Conclusion

What is clear is that we are continuing to make strides on that road towards perfect healthcare, thanks to the amazing work of scientists in many different sub-disciplines of medicine & life sciences. Time will tell which of the above will end up making the greatest impact, but then again, it's not really a competition, and many of the building blocks listed above are synergistic with each other (and with other future advances such as the ones I mentioned in my earlier paper).

Do I personally feel more optimistic than I did back in 2021? Perhaps a little. We certainly live in an interesting time, where many advances are coming together in ways that were unimaginable a few decades ago. I have little doubt that future generations will look back at this era as a revolutionary period in the field of medicine, and innovations that are cutting edge now are likely to become fully ingrained or even indispensable in years to come.

For many of us, time is not on our side, however. It is frustrating to know that many of these future advances will make it to the clinic too late to make a difference to us and our loved ones. Then again, we are far more fortunate compared to the generations that came before us when it comes to the healthcare tools at our disposal. In a way, the single biggest factor that drives inequity in access to healthcare isn't income, gender, or geographic location: it is time, the era in which we live. Future generations are likely to have access to far more advanced treatments than we do, just like we (on average) have access to far more advanced treatments than past generations did.

If she had been born 50 years later, would my mother's condition have been reversible? Quite likely. Would my sister's cancer have been detected before it had a chance to take hold, and would it have been fully curable upon detection? Definitely a possibility. On the other hand, if she had been born 50 years ago, would she have been given the option to undergo a repeat awake craniotomy to remove the majority of the residual tumour mass, after having her brain's activity mapped through a functional PET scan? Almost certainly not.

It's all relative, and we just have to accept where fate (or sheer random luck) has placed us on the road towards perfect healthcare, a road we as a species started walking down many thousands of years ago, and which we are likely to continue following for thousands of years to come.

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References

[1] Data collected by Ipsos through the Global Advisor online platform among adults aged 16-74 in France, Germany, Italy, Spain, UK, Canada, Japan, Brazil, Peru, Thailand and Saudi Arabia and adults 18-74 in the US, from 6th to 14th February 2023.

[2] Data collected online from 208 physicians (different specialties) in US in February 2023 by Medefield on behalf of Ipsos.

[3] Ipsos Oncology Monitor, based on 61 doctors completing online patient record forms between Jul 2021 and June 2022 in the Philippines.