The remarkable speed at which both Moderna and Pfizer / BioNTech were able to develop their highly efficacious Covid-19 vaccines has brought mRNA-based technology into the mainstream. Both Moderna and BioNTech have been developing mRNA-based vaccines for a range of conditions for many years, but currently, none of these have been approved. However, could their success in developing Covid-19 vaccines lead to a renewed enthusiasm for mRNA-based cancer vaccines?
Cancer vaccines have been in development for many years, but high-profile failures and limited results have meant there has not been a great deal of interest in this approach in recent years. However, following the success of the Covid-19 vaccines, investors may be much keener to back these technologies, both due to the demonstrated safety in a large cohort of patients, as well as the impressive efficacy of this approach. Furthermore, the considerable revenue both Moderna and BioNTech can expect from their Covid-19 vaccines means that these companies will have the funds needed for clinical trials.
While the mRNA-based vaccines against Covid-19 (and those in development for other infectious diseases) focus on prevention, cancer vaccines are designed to treat tumours by stimulating an immune response and are unlikely to be used as a stand-alone therapy. Moderna currently has two cancer vaccines in clinical trials (partnered with Merck); the most advanced of these, mRNA-4157, is a personalised vaccine that delivers neoantigens selected from the patient’s tumour and is being tested in a Phase II trial for the adjuvant treatment of melanoma and in a Phase I trial for the treatment of solid tumours, in both cases in combination with Merck’s Keytruda. Interim results from the Phase I trial appear promising, with an overall response rate of 50% in a small sample of patients with head and neck squamous cell carcinoma. Meanwhile, BioNTech has several cancer vaccines in development and early-stage clinical trials. One, BNT111, is currently being tested in a Phase I trial in melanoma patients and is composed of four melanoma antigens. However, interim results were underwhelming. A second candidate from BioNTech in collaboration with Roche / Genentech is a personalised vaccine being tested in advanced melanoma patients in a Phase II trial in combination with Keytruda, with results expected later this year.
Despite the successes of these mRNA-based vaccines against Covid-19, cancer vaccines using similar technologies are still unlikely to be available for several years. Cancer vaccines are considerably more challenging to develop than those designed to prime the immune system against infectious agents. Tumours are much more heterogenous and it may be that a personalised approach is required, in which case the selection of the most appropriate neoantigen is vital and there are additional time constraints that must be considered. Additionally, clinical trial endpoints are necessarily much longer, especially for therapies utilised in the adjuvant setting. Finally, now that the efficacy of mRNA vaccines against the novel coronavirus has been demonstrated, companies may choose to go after much lower-hanging fruit; the seasonal influenza vaccine, for example, would be a highly lucrative space. That being said, this is likely to be a much more active area of research, with a considerably increased investment that could drive important advances in cancer vaccines.