The new personalized vaccine developed by Moderna and Merck has passed a major trial and reduced the risk of melanoma returning or spreading. A result that opens a new path for patients and has made Moderna shares skyrocket on Wall Street.
Moderna and Merck’s melanoma vaccine passes phase 3 and reduces the risk of the tumor returning or developing metastases. It is the result of the international INTerpath-001 study, conducted on 1,137 patients with high-risk cutaneous melanoma who had already undergone complete surgical removal. The experimental treatment, autogenous intismeranwas administered together with the immunotherapy pembrolizumab, the active ingredient of the drug Keytruda, and achieved both of the main objectives of the study: survival free from relapse and survival free from distant metastases. The news, which arrived on August 19, marks an important step in research on cancer vaccines: it is the first time that a personalized mRNA-based cancer therapy has successfully reached phase 3. It is not a vaccine designed to prevent melanoma from appearing: it is administered after surgery, when the tumor has been removed, with the aim of helping the immune system to recognize and eliminate any tumor cells remaining in the body, thus reducing the risk of the disease returning or spreading. The characteristic that makes this therapy particularly interesting is its being personalized. The individual patient’s tumor is analyzed to identify the mutations that characterize it and, based on this information, the mRNA treatment is designed. In other words, the vaccine is built starting from the molecular identikit of that particular tumor, to provide the immune system with the information necessary to recognize its cells. The technology is that ofMessenger RNAwhich has become familiar with Covid-19 vaccines, but here it is used for a completely different purpose: not to prevent an infection, but to stimulate an immune response against cancer. Autogenous Intismeran was developed by Moderna in collaboration with Merck, and the result of phase 3 could represent the decisive step towards a new generation of personalized immunotherapies against melanoma.
It is not yet “the vaccine against cancer”: what the study really shows
The result is important, but it does not mean that a vaccine capable of preventing melanoma in the general population has been inventednor that we are faced with a therapy already available in hospitals. Autogenous Intismeran is still an experimental treatment. The result announced by Moderna and Merck is, for now, a high-level preliminary result: the companies communicated that the study reached the expected endpoints, but specified that the detailed data will be presented at an upcoming international medical congress. The companies now intend to deal with the regulatory authorities in view of the authorization requests. It is anything but a formal distinction. Saying that there is a therapy reduced risk of relapse is not automatically equivalent to demonstrating that it increased overall survival. And in fact, in the phase 3 results released on August 19, complete data on overall survival are not yet available. Scientists underline this very point: the results necessary to establish whether treated patients live longer are not yet available. The result is however relevant for at least two reasons. The first is clinical: after the removal of a high-risk melanoma, the problem is not only to eliminate the visible tumor mass. Tumor cells that cannot be identified with conventional instruments may remain in the body and are capable of giving rise to a recurrence or metastasis over time. The idea of personalized therapy is to exploit the immune system to intercept those very cells. The second reason is technological. It is the first time that an mRNA-based personalized cancer therapy has successfully passed a phase 3 trialas communicated by the companies. And the result comes in a field in which therapeutic vaccines have been tested against various tumors for years, with still very variable results. The comparison of the study is also significant: it was not a question of demonstrating that the vaccine was better than no therapy, but that adding intismeran to Keytruda produced a greater benefit than immunotherapy alone. Keytruda, pembrolizumab, is a monoclonal antibody that allows the immune system to recover some of its ability to recognize and attack tumor cells. The personalized vaccine tries to add a second layer: provide the immune system with a more specific target, built on the genetic characteristics of the individual patient’s tumor. The mechanism, therefore, is interesting precisely because it brings together immunotherapy and personalized medicine. However, a question that is anything but secondary remains: producing a different therapy for each patient is much more complex than producing millions of identical doses of a traditional vaccine. It is necessary to analyze the tumor, identify the relevant mutations, design the mRNA sequence and produce the treatment. The possibility of making this process sufficiently rapid, reliable and sustainable on a large scale will be one of the decisive challenges if the therapy reaches clinical use. And then there is the issue of cost. For now there is no price, because there is no commercial authorization yet. But the extreme personalization of therapy makes it clear that the economic question, together with the organizational one, will be an integral part of the future discussion on access.
Moderna flies on the stock exchange, but the market is already betting on the future
The scientific dimension of the news was immediately accompanied by the financial one. And in this case the market reacted spectacularly. August 19th Moderna shares gained around 160% during the session and closed with a rise of 177%according to data reported by the US financial press. The stock reached $174.38 and the company’s capitalization increased by tens of billions of dollars in a single day. For Moderna it is more than a normal reaction to a positive result. The company has for years been almost completely identified with the success of the anti-Covid vaccines and the subsequent collapse in demand. The search for a second “industrial leg”, through innovative drugs and vaccines for other diseases, has become one of the central issues for the company’s future. The success of the program against melanoma therefore offers investors something that the market has been waiting for for some time: the concrete possibility that the mRNA platform can also produce value beyond Covid. The leap, however, also shows how capable the stock market is of anticipating the future. The market is not only evaluating the revenues that this therapy could generate in melanoma, but the possibility that the same technology could be adapted to other tumors. In fact, the intismeran program is already being studied in other oncological indications, including lung, kidney and bladder tumors. Professor Paolo Ascierto, an Italian luminary from the Pascale University of Naples who himself administered the Moderna vaccine within the phase 3 trial, has in fact spoken of a possible turning point in oncology. In fact, if it were demonstrated that a platform capable of building a treatment on the genetic “signature” of a single tumor can be successfully applied to multiple tumors, mRNA could transform from a technology used mainly in infectious vaccines into a platform for a new generation of personalized oncological therapiesIt is therefore an important day, but not yet the arrival point. For high-risk melanoma patients, the news means that an experimental strategy born from the meeting between tumor sequencing, mRNA biological intelligence and immunotherapy he passed the most difficult step. For oncology research it means that the idea of building a “tailor-made” therapy for each person’s tumor has received one of the most important clinical confirmations so far. For Moderna and Merck it means something even more concrete: the promise of transforming a technology created to teach the immune system to recognize a virus into a tool capable of teaching it to recognize your tumor. Now, however, the word passes to complete data, independent experts and regulatory authorities. Because the real revolution will not be that of a day on the stock market. It will be to understand if this therapy will be able to transform a statistical result into more years without disease, fewer metastases and, above all, more lives saved.
