A well-executed communications plan. On September 6, a “press relations manager” of a French biotechnology company sent a first email to alert about “an essential advance in the treatment of metastatic lung cancer”. A press point is planned for Monday, September 11 and “around ten media outlets have already confirmed their participation,” he tells us. A not-so-subtle incentive not to miss this announcement, which should undoubtedly be widely relayed.
Two days later, second email from the same company. The invitation to the “e-press conference” mentions a therapeutic anti-cancer vaccine, “the most advanced in the world in terms of clinical development”, “a hope and a new therapeutic weapon for cancers with poor prognoses”. It’s hard to be more enticing. A seemingly important advance, published in a prestigious journal, Annals of oncology, developed by a French biotech: the information will, without a doubt, make the headlines. And in fact, a few hours after the press conference, articles flourished on the Internet. “A promising cancer vaccine…”, “a very encouraging step forward”, “a vaccine that could save the lives of thousands of people”…
The communications operation worked perfectly. If therapeutic vaccines are undeniably a promising avenue against cancer, did the information presented this Monday deserve such an echo? Looking closely, the data presented by OSE immunotherapeutics are not new, and above all, they hardly seem convincing. They were not considered conclusive by the National Medicines Safety Agency (ANSM). The company had in fact submitted an “early access” request to the French health products watchdog at the end of last year. This procedure makes it possible to make innovative products accessible to French patients even before the therapy has a marketing authorization issued by the European Medicines Agency. To obtain this early access, the product must still provide a real breakthrough for patients.
“Major methodological biases compromising the reliability of the results”
In this case, it was not the modesty of the announced benefit (a median survival of 3.5 additional months for those treated) that made the ANSM raise eyebrows, but the quality of the data used to demonstrate its reality. Its experts closely studied the results of the Atalante-1 clinical trial, the same as those presented to the media at the beginning of the week. They concluded, in an opinion delivered on February 27, that these data “could not attest to the strong presumption of effectiveness and safety of the drug […] in the claimed therapeutic indication”. Clearly, the information presented was not conclusive, and early access, normally conditional on a favorable opinion from the ANSM then from the High Authority of Health, was refused from this first filter. In question, “major methodological biases noted in the context of the study submitted […]compromising the reliability of the results”, indicates the ANSM in his opinion.
If the study was initially “well constructed”, according to a specialist in the analysis of clinical trials, the company was unlucky. In April 2020, when the protocol had already been launched since 2016, the inclusion of new patients had to be stopped due to the pandemic. Only 219 patients were recruited, compared to 363 planned. A reduction which “impacted the statistical power of the study to highlight a statistically significant difference in overall survival”, underlines the ANSM.
As a result, the study authors subsequently identified a smaller group of 118 patients who had already received chemotherapy and immunotherapy, and who were in relapse. It is on this specific group of patients that the results highlighted by OSE immunotherapeutics were obtained, including a greater median survival in patients who received the vaccine (11.07 months) than in patients treated with chemotherapy (11.07 months). 7.47 months). “This is an interesting signal, even if the number of participants is too low for us to be certain that it is not a false positive,” recognizes Professor Benjamin Besse, director of research. clinic at Gustave Roussy and principal investigator of the study.
“Exploratory results”
In fact, the ANSM indicates that “the results presented should only be considered exploratory and need to be confirmed by a new effectiveness study”. The agency thus notes, among other remarks, that the choice to retain a restricted group of patients a posteriori can introduce selection bias. She also notes that vaccinated patients were “more likely to have received a subsequent line of treatment than patients in the control group”. This can make the analysis of the specific effectiveness of the vaccine more difficult. Nicolas Poirier, the general director of OSE immunotherapeutics, however, sees this as good news: “Patients treated with our vaccine have few side effects and a better quality of life. So when the tumor starts to progress again, doctors can introduce a new line of medication. Conversely, those who are undergoing chemotherapy are often so degraded that it is more difficult to add treatment,” he explains.
For the biotech manager, the need to relaunch a clinical trial could be explained simply by regulatory reasons. “Our results are very positive, but health agencies in Europe and the United States are asking us for a new study to verify that there is no bias. From a medical point of view, the quality of the scientific journal which accepted our study speaks for itself”, he underlines. The published article, however, remains cautious in its conclusions. The authors indicate that the data presented “suggest” a “potential” improvement in patient survival, and also indicate that further studies will need to take place. “The demonstration of effectiveness cannot be done statistically since the protocol has not been completed. But this initial work will subsequently prevent us from including patients for whom no or little benefit is expected. “, confirms Professor Besse.
Under these conditions, why did you communicate so widely on this publication? “This is the first time in the world that a phase 3 study with a cancer vaccine has been published with positive results, and it seemed obvious to us that we had to share them with the entire scientific and medical community” , assures Nicolas Poirier. Waiting for the results of the new phase 3 trial was not an option for this biotech: “It will take another three years, these data will not be available before the end of 2026,” he explains. A new study which will perhaps provide indisputable demonstration that this vaccine does indeed present a benefit compared to existing treatments for responding patients.
Beyond the robustness of the data, the very presentation of the results to the general public raises questions. A figure, put forward by the company, was widely adopted: its product would reduce “the risk of death by 41%”. “This gives the impression that 41% of patients are not going to die, even though this is a reduction in the relative risk of death,” indicates Professor Besse. This reading is, however, much more spectacular than the mere mention of a median survival of 3.5 additional months thanks to the treatment…