Could cancer be the next mRNA breakthrough?


mRNA vaccines achieved their first success against COVID-19, but could a bigger target be next? Ben Hargreaves examines whether the technology could provide a new tool against cancer, and how close current companies are to achieving a breakthrough.

With the arrival of the COVID-19 pandemic, the pharmaceutical industry had to react quickly to develop a vaccine. Speed was a priority among those developing a potential vaccine candidate. Traditional vaccines, such as those produced by AstraZeneca and Johnson & Johnson, were working with a platform for vaccine candidates that had already been tested against other infectious diseases. By contrast, mRNA vaccines developed by Moderna and BioNTech had to be developed from scratch, and quickly. Moderna stated that it took the company 63 days to move from sequencing to human trials. In December 2020, Moderna’s vaccine became the second COVID-19 vaccine, behind BioNTech-Pfizer’s mRNA vaccine, to receive emergency use approval from the US Food and Drug Administration (FDA).

Now that the worst of the pandemic has passed, the speed with which the mRNA vaccines were developed has the pharma industry wondering where else this technology can be applied. Moderna’s pipeline of mRNA therapeutics includes respiratory diseases, infectious diseases, and a broad area, just called ‘therapeutics’. BioNTech’s pipeline contains vaccines for infectious diseases, including for work on HIV and tuberculosis, as well as a number of potential treatments for cancer. It is the latter therapeutic area that is creating the biggest interest for the future of mRNA therapies.

The next step

According to the US National Cancer Institute, there are currently dozens of clinical trials testing mRNA treatment vaccines in people with various types of cancer. The vaccines are being developed both as standalone treatments and in combination with existing therapies, with the potential that the mRNA technology could help heighten the immune response against cancer cells. 

To date, there are currently no mRNA cancer vaccines approved, but with the success seen with COVID-19, there is an expectation that a breakthrough could happen quicker than with other treatment mediums. As a result, there is more funding being diverted into the area compared to prior to the pandemic: “There’s a lot of enthusiasm around mRNA right now. The funding and resources that are flowing into mRNA vaccine research will help the cancer vaccine field,” Patrick Ott, clinical director at the Center for Personal Cancer Vaccines, Dana-Farber Cancer Institute, told the National Institutes of Health.

mRNA vaccines function by delivering stable forms of mRNA to the body. Once in the body, the mRNA instructs cells that take up the vaccine to produce proteins that can stimulate a response against the same proteins that are present in viruses or tumour cells. In the COVID-19 vaccines, this saw the mRNA instruct cells to produce a version of the ‘spike’ protein that appears on the surface of SARS-CoV-2. In cancer, the same technique could be used to teach the immune system to differentiate between cancer cells and the rest of the body, such as by producing proteins that are normally found in cancer cells, but not in healthy cells.

Building a head of steam

In a sign of how the technology is developing in cancer treatment, there have been several announcements in recent months that point to progress being made. At the end of last year, Moderna and Merck were able to post positive data from a phase 2b trial, where a cancer vaccine was tested alongside Merck’s Keytruda (pembrolizumab). The combination treatment was found to reduce the risk of death or disease progression by 44% when compared to treatment with Keytruda alone in patients with high-risk melanoma.

In a sign of how much interest Merck has in this potential combination, the company paid $250 million to take up the option to jointly develop and commercialise the mRNA vaccine created by Moderna. If the results in the phase 2b trial can be replicated in later-stage trials, it is clear to see why Merck is prepared to pay to gain greater access to the treatment. Keytruda is already Merck’s biggest selling treatment and, according to Evaluate, the checkpoint inhibitor is set to be the biggest selling individual product in 2023, with estimations of global sales reaching almost $25 billion. Combining Keytruda with Moderna’s cancer vaccine could see the efficacy of the treatment boosted in further treatment areas, solidifying its position at the top of the sales pyramid.

How soon is now?

It is not just companies eyeing the potential for mRNA cancer vaccines. At the beginning of this year, the UK government announced a partnership with BioNTech, which added to a previous agreement with Moderna to construct a manufacturing facility for mRNA vaccines. The deal with BioNTech saw the UK government secure access for 10,000 patients to receive personalised cancer therapies. The therapies will be provided as part of clinical trials through to 2030, but the partnership also contains a provision for this to be extended into commercial therapies, if BioNTech receives an approval during this period. According to the partners, the aim is for the first cancer patient to be treated in the second half of 2023. 

“The UK successfully delivered COVID-19 vaccines so quickly because the National Health Service, academia, the regulator, and the private sector worked together in an exemplary way. This agreement is a result of the lessons learnt from the COVID-19 pandemic, as we all experience that drug development can be accelerated without cutting corners if everyone works seamlessly together towards the same goal,” stated Ugur Sahin, CEO of BioNTech, on the value of the partnership.

More than speeding access and development of mRNA cancer therapies, BioNTech will also invest in an R&D hub in Cambridge, UK, and set up a regional headquarters in London. For the UK, this means the establishment of mRNA expertise within the country, particularly within the biotech hub in Cambridge, which could pay dividends in the years to come. The government’s decision to sign a 10-year alliance with Moderna to develop a manufacturing centre in the UK, capable of producing 250 million vaccine doses per year, also points to the country foreseeing a big future for the therapeutic area in the coming years.

The next stage for the technology will be the same step that both Moderna and BioNTech took during the pandemic – receiving an approval for an mRNA vaccine outside of COVID-19. If either company can prove efficacy in phase 3 trials, the investment and interest in the area will grow exponentially. Moderna and Merck plan to initiate a phase 3 study in melanoma during 2023, and to “rapidly expand to additional tumour types,” suggesting it might not be long before the industry has an answer to whether mRNA treatments can become a real part of cancer treatment.

20 February, 2023