On April 8, The Guardian published an article with the headline “Cancer and heart disease vaccines ‘ready by end of the decade’.” It is based on an interview with Moderna Medical Director Paul Burton, and its retelling has gone viral. Ilya Yasny explains why such promises sound unprofessional, and which of them we can realistically hope for in the field.
Moderna, alongside other companies such as Pfizer/BioNTech, AstraZeneca, Novavax, and Johnson&Johnson, successfully created and introduced a vaccine against the SARS-CoV-2 coronavirus to the global market. Despite not being a pharmaceutical giant, Moderna is still a large startup, much like Novavax. The coronavirus vaccine is the company's first product on the market, and the first product for which they conducted Phase 3 studies, the necessary extensive research to bring the product to market. Prior to the pandemic, the rest of Moderna's nascent, albeit extensive and promising, development portfolio consisted of five products in the early stages of clinical trials.
The development of coronavirus vaccines during the pandemic was a remarkable event in the history of biopharmaceuticals. At the onset of the pandemic, no expert predicted that a vaccine would be available on the market in less than three years. However, within a year, vaccines became available, which raises the question of whether this was achieved through cutting corners, unprecedented luck, or a demonstration of modern science's capabilities. The answer is a combination of all three, with the latter being the more significant factor.
The regulatory agencies, particularly the U.S. Food and Drug Administration (FDA), responded promptly by engaging in discussions with vaccine developers and enabling progression to subsequent development stages as data accumulated. The substantial financial and human resources invested in the fight against the virus allowed for the simultaneous execution of many processes, which would typically occur sequentially. For instance, large-scale production commenced before the Phase 3 clinical trial results were available, which is not the norm since the study may fail. Good fortune also played a role, as the virus did not mutate as rapidly as the flu, and the antibodies generated through vaccination were capable of suppressing it, unlike in the case of HIV.
Good fortune also played a role, as the virus did not mutate as rapidly as the flu
Yet, the scientific groundwork established over several decades remains the crucial factor. Trials with mRNA vaccines and adenoviral vectors commenced in the 1980s, and since then, several efforts to develop a functional vaccine have been mostly unsuccessful. The initial RNAi medications that were moderately safe and effective for treating rare liver disorders were introduced to the market in 2018. By 2020, a significant accumulation of technology and expertise had occurred, facilitating the development of vaccines for the coronavirus.
Another contributing factor to the rapid development of the COVID-19 vaccine was the high rate of infection during the pandemic. With hundreds of thousands of people getting sick every month, it was relatively easy to recruit large groups of 20,000-40,000 individuals to test the vaccine's effectiveness. This allowed researchers to quickly observe the difference in the number of cases between the vaccinated and control groups, providing evidence of the vaccine's efficacy.
Will it be possible for Moderna and other companies to replicate the success they had with the coronavirus vaccine for other diseases? In short, yes, but it is unlikely to be achieved as quickly as suggested by Paul Burton.
Recruiting a large number of people to test the efficacy of vaccines for other diseases is difficult compared to the COVID-19 vaccine, as it is not possible to quickly assemble large groups of people. In normal circumstances, enlisting even a few thousand people for testing can take several months.
Furthermore, apart from pharmaceutical companies, there are few entities that are willing or able to invest significant amounts of money into risky research and development. Therefore, the success of mRNA and adenoviral vector-based vaccines during the pandemic, along with the subsequent large-scale production, does not necessarily guarantee that similar success will be achieved with other diseases at the same speed and certainty.
Apart from pharmaceutical companies, there are few entities that are willing to invest significant amounts of money into risky research and development
Clinical trial statistics show that only a small percentage of new drugs, around 10%, successfully make it to the market. In the field of oncology, the success rate is even lower at around 5-6%. Despite this, Moderna has a broad range of development projects, which increases the likelihood of success in at least some areas. Currently, the company has 48 projects in its development portfolio, with 25 in the clinical stage and five in the late stage (phase 3). Recently, Moderna announced the results of phase 3 clinical trials for a vaccine against respiratory syncytial virus (RSV) and influenza.
The RSV vaccine showed efficacy similar to that of recently published results by other competitors, while the flu vaccine had some shortcomings. It was only as effective as the traditional vaccine against some strains of type A, and failed to demonstrate sufficient effectiveness against type B strains. Nonetheless, Moderna's platform is highly adaptable, allowing for the swift creation, testing, and production of a new version of the vaccine within a few months. This has been demonstrated by the development of booster shots against Omicron variants of SARS-CoV-2.
What about a vaccine for cancer and cardiovascular disease?
The RNA drugs being developed for cancer can be referred to as vaccines, as they trigger the production of antibodies and cellular response against tumor antigens, which are essentially the “wrong” molecules present in tumors that can be targeted by the immune system. In this way, they function somewhat like vaccines against infectious agents. However, these are not preventive vaccines, but rather therapeutic ones that are administered after a person has already become ill. The long-term efficacy of therapeutic vaccines remains uncertain, but studies on other immuno-oncology drugs, which also include vaccines, suggest that if there is no cancer recurrence within a year, the likelihood of the cancer returning is very low due to the heightened activity of the immune system. Nevertheless, these vaccines do not confer immunity against other types of cancer.
Creating a preventive cancer vaccine would be an attractive idea, but it is unlikely to happen before 2030. Even if research were to begin now, it would take several years of observation to determine whether such a vaccine is truly effective.
Creating a preventive cancer vaccine would be an attractive idea, but it is unlikely to happen before 2030
But for cardiovascular, respiratory, or rare hereditary diseases, the term “vaccination” may not be appropriate. Instead, mRNA therapy is used, in which the mRNA enters the cell and starts producing the necessary protein, leading to an improvement in the disease's course or even a complete cure.
Moderna released preliminary findings on its melanoma vaccine at the end of 2022, indicating positive results. However, these results are not sufficient to claim a significant breakthrough. With a limited number of patients and only one year of follow-up, the effectiveness of the drug remains uncertain until the upcoming Phase 3 trials. It is important to note that this therapy targets only one of hundreds of cancer types and does not guarantee a complete cure for all patients, but rather aims to enhance existing treatments. This personalized therapy is not suitable for everyone, as it depends on identifying specific mutations in the individual, which carries the risk of errors, lack of information, and the diverse nature and evolution of tumor cells. These factors are among the reasons why personalized cancer vaccines have yet to prove entirely effective.
Moderna released preliminary findings on its melanoma vaccine. But it's not a breakthrough
Moderna has several other anti-cancer products, but they are all early-onset and therefore very risky.
Moderna's early-stage development of a therapy for cardiovascular disease employs an approach that has previously failed in clinical trials. While there is a possibility that Moderna may achieve success with this therapy, it remains a relatively specialized area of research. Creating a universal “vaccine” for all cardiovascular diseases is unlikely to be feasible.
However, the field of biopharmaceutical development extends beyond just Moderna and RNA-based products. Each year, new treatments emerge utilizing both traditional approaches, such as low molecular weight substances and antibodies, as well as cutting-edge technologies like gene and cell therapy, or Zolgensma. These therapies have the potential to cure previously untreatable diseases, but they remain expensive and niche products for rare diseases, often costing millions of dollars. Thousands of developments are underway for more common diseases like autoimmune and cardiovascular diseases, among others, and it is likely that some of these will prove successful by 2030. However, it is unlikely that the issues surrounding cancer, autoimmune diseases, and infectious diseases will be fully resolved in the next seven years.
New therapies have the potential to cure previously untreatable diseases, but they remain expensive and niche products for rare diseases
Regrettably, the cost of new developments is very high, ranging from tens to hundreds of thousands of dollars, and in some cases even millions, making them unaffordable for people in developing countries. However, these countries have more pressing issues such as hunger, lack of access to clean water, and infectious diseases. We can only hope that as these pressing issues are addressed, the cost of new developments will decrease and become more accessible to everyone, similar to the way antibiotics were initially expensive but became more affordable over time.
So, it is possible that the director of Moderna is doing this interview as part of a PR campaign to generate public and investor interest, particularly in light of declining COVID vaccine sales. While the public may quickly forget the details of Burton's promises, the interview is likely to generate immediate attention. Moderna's CEO, Stephane Bancel, has recently testified before the U.S. Congress to defend the company's pricing policies and the broader pharmaceutical industry. This is an important mission as politicians and the public are quick to criticize pharmaceutical companies, despite their role in saving millions of lives during the pandemic and developing new drugs. However, some may view Burton's statements as lacking in professionalism.