The Cost of Curing Disease: Why Some Gene Therapies Cost More Than Others

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In 1985, researchers at the National Institute of Health (NIH) showed that it was possible to introduce new genetic material into cells from individuals with a genetic disease (in this case it was ADA deficiency, an inherited immunodeficiency syndrome), and that the cells would incorporate the foreign DNA, alleviating the consequences of the disease. This was a major breakthrough and opened up the possibility of using genes as therapy.

5 years later, this concept was proven that it could work in humans when the first successful gene therapy was performed in the US for a 4-year-old with ADA deficiency.

Since then the world of gene therapy has blossomed into a multi-billion dollar industry, helping to treat a plethora of genetic conditions and with the FDA proclaiming that they expect to be approving 10–20 cell and gene therapies a year from 2025.

An unfortunate characteristic of gene therapies are their sky-high costs to the patient. However, over the past couple of years the disparity in costs within the gene therapy industry, has been epitomised by the tale of two drugs; Zolgensma and the Oxford-AstraZeneca COVID vaccine.

Almost exactly a year ago, the NHS, the UK’s national health service, announced a deal with pharmaceutical giant, Novartis, which would see a new gene therapy, Zolgensma, be made available in the UK.

Zolgensma works by replacing the defective SMN1 gene with a new, working copy in children with spinal muscular atrophy (SMA), a degenerative condition that targets the motor neurons, resulting in those affected having difficulty moving, swallowing and eventually breathing. These symptoms make SMA the deadliest genetic condition in babies and young children.

Zolgensma is a remarkable drug for a number of reasons; Firstly, it’s efficacy in such a devastating disease; the latest data published on the 14th of March this year stated that:

Children treated preemptively with Zolgensma are standing and walking, with few or no signs of neuromuscular disease. Many of these children achieve patterns of motor development indistinguishable from their healthy peers without SMA

Kevin Strauss, M.D., Medical Director, Clinic for Special Children in Pennsylvania

Secondly, administration of Zolgensma requires only a single shot to be effective. No repeat treatments. No follow up injection. A single shot, administered once in a patient’s lifetime. And finally, and perhaps most eye-catchingly, Zolgensma was recently labelled ‘the most expensive drug in the world’. A title well-deserved, as a single dose of the gene therapy comes in at a whopping $2.125 million.

Despite the vast amount of money Novartis is demanding for their drug being somewhat of an outlier, eye-watering prices are an all-to-common occurrence in the world of gene therapy.

At a similar time to when Zolgensma was approved by the NHS (March 2021), another type of gene therapy was being rolled out to all corners of the world; Oxford-AstraZeneca’s COVID-19 vaccine (although some disagree, most consider Pfizer and Moderna mRNA-based vaccines not to be gene therapy). The Oxford-AstraZeneca vaccine uses a viral vector to deliver a gene encoding the infamous coronavirus spike protein, allowing the body to develop an adaptive immune response to the disease.

By November of that year, it was announced that Oxford-AstraZeneca had supplied 2 billion doses of their vaccine worldwide, with approximately two-thirds of these having gone to low- and lower-middle-income countries.

But, if gene therapy is so expensive, how did all of these countries afford to supply their entire populations with not just one, not just two, but, in some cases, three doses each? The simple answer is; the COVID-19 vaccines did not cost as much as drugs such as Zolgensma, in fact they cost around a million times less, $2-3 each.

So then why is there such a disparity in the costs of some gene therapies vs others?

Until October 2021, AstraZeneca sold millions of doses of their vaccine at cost price, taking no profit from its sales. Since then they have adjusted to selling to richer countries for a slight profit, however, as per their agreement with the University of Oxford, they maintain the production cost price to low-income countries. Although this is notable, and speaks to the moral compass of the Oxford-AstraZeneca team, it does not explain the vast distance between the single dose values of the two gene therapies.

The next thought is that drugs such as Zolgenesma must use some sort of special, cutting edge technology or ingredients that makes each dose of it astronomically more expensive to manufacture. This is, for the most part, incorrect. Although Zolgensma requires a larger transfusion with a greater cost of administration, both of the drugs use inexpensive viral vectors to transport the selected gene to the cells. The research and manufacturing of Zolgensma may cost a lot (STAT estimates it at “a few hundred million at most.”), but it certainly doesn’t cost millions of times more than any other gene therapy.

The reason for the exorbitant cost of Zolgensma comes down to three factors:

1. Single dose administration – many other gene therapies require more than one dose to be effective, this means that whereas the price per dose is much cheaper, the absolute cost is still relatively high.
   
2. Potential to save lives – Zolgensma has the potential of not only saving children’s lives, but also rescuing them from a life wrought with pain and disability. How can one even attempt to put a price on this? Unfortunately, this rhetoric is used by companies like Novartis in justifying such high prices.
   
3. Small market size – this is perhaps the most important factor of all, and why most other gene therapies are also so expensive in comparison to the COVID-19 vaccine. The charity Spinal Muscular Atrophy UK, reported that in the UK, 42 babies were born with SMA in 2017. This is roughly 1 in every 16,000 babies. Compare this to the Oxford-AstraZeneca COVID-19 vaccine, for which almost every person in the UK is eligible to receive.

In an effort to justify the price a Novartis spokesperson stated:

The Wholesale Acquisition Cost (WAC) of Zolgensma is $2.125 million – less than 50% of the current 10-year cost of the current standard in chronic SMA therapy in the US, and within the range of rare-disease cost-effectiveness thresholds used by the Institute of Cost Effectiveness Research. Over time, it is expected to save costs in the healthcare system for the treatment and care of patients with SMA, and we are partnering flexibly with payers to ensure access and affordability

Novartis Spokesperson. Source: FactChecker

What does this mean for the future of gene therapy and the ageing field?

Unfortunately, ageing is a condition that still impacts every single person on the planet. Therefore, if a gene therapy that ameliorates the consequences of ageing is discovered, the drug will have a potential audience of the entire global population (plus potentially any lucky animals we want to stick around). Through economies of scale the gene therapy should be able to be provided for a low price.

However, this doesn’t necessarily mean that it will be. How much would you be willing to pay to live an extra 10, 20, 50 years? Thousands? Millions? Billions? This is the question that ‘big pharma’ will be seeking to find an answer to in the near future, and which will almost certainly play a role in the cost of such a treatment, if, and when, it arises.