The personalized vaccine, known scientifically as intismeran autogene, was evaluated in a pivotal late-stage trial. When paired with Merck’s blockbuster immunotherapy Keytruda, the combination therapy reduced the risk of recurrence or death in certain melanoma patients by 42% compared with the administration of Keytruda alone.
Further compounding the encouraging clinical picture, the data also demonstrated that the experimental shot alongside Keytruda reduced the risk of cancer spreading to distant parts of the body, or death, by 38% compared to the use of the immunotherapy by itself.
Providing a granular breakdown of the findings, the companies reported that approximately 82% of patients who received the personalized cancer vaccine in tandem with Keytruda were alive and without their melanoma returning two years after receiving the treatment. This compared favorably to 70% of those patients who received Keytruda alone.
Medical professionals immediately hailed the findings. Dr. Hussein Tawbi, a prominent melanoma expert and trial investigator at the University of Texas MD Anderson Cancer Center, called the results a huge development for patients. He noted during discussions of the trial that the added clinical benefit of the vaccine also comes alongside much milder toxicity, or side effects such as injection-site pain, compared to many other conventional cancer treatments.
The detailed phase 3 trial results were scheduled to be presented formally at the upcoming European Society for Medical Oncology conference over the weekend, bringing international scientific scrutiny to the therapy.
Ahead of the full data disclosure, Dr. Dean Li, president of Merck Research Laboratories, emphasized the difficulty of the clinical hurdle the companies set out to clear. In an interview, Li pointed out that whenever a novel therapy is added on top of a treatment that already works remarkably well, such as Keytruda, demonstrating additional benefit can often prove exceedingly difficult. However, he noted that the trial encountered no problems establishing that additional benefit in this specific case.
The clinical advantage of the vaccine appeared even more pronounced after the completion of the six-month vaccine regimen. A separate analysis of the trial data revealed a striking 58% reduction in the risk of recurrence or death during that evaluated window. Despite these stellar metrics, company executives noted that it remains too early to definitively determine whether the innovative treatment ultimately helps patients live longer overall.
Wall Street analysts were quick to contextualize the paradoxical market reaction, pointing to sky-high investor expectations that had been baked into the stock price ahead of the release.
Evan Seigerman, an analyst at BMO Capital Markets, addressed the market turbulence in a research note published on Thursday following the leak. He asserted that the relative reduction in recurrence and death is clinically meaningful, adding that the sharp downward stock reaction likely reflected inflated expectations ahead of the full data release rather than a genuine indictment of the underlying efficacy of the combination therapy.
Oncologists and market investors alike have long viewed the targeted vaccine as a potential watershed moment in oncology, with broader ambitions to treat a wide array of other human cancers in the future. Currently, Merck and Moderna are actively studying the vaccine in several ongoing clinical trials targeting other formidable tumors, including non-small cell lung cancer, bladder cancer, and renal cell carcinoma.
Even so, Merck’s Dean Li remained pragmatic about the road ahead, acknowledging that the companies still have substantial work remaining to prove that the product can achieve consistent efficacy across diverse tumor types.
Using a vivid metaphor to describe the current state of clinical development, Li remarked that while he can dream of creating a log cabin, the research teams currently have some wood chops and have just knocked down one tree. Knocking down a single tree, he observed, does not instantly yield a cabin or a village.
Despite the necessary work ahead, the vaccine is drawing closer to potentially entering the commercial market for the very first time and directly reaching melanoma patients in need. In an interview conducted prior to the formal data release, Moderna CEO Stéphane Bancel stated that the company is actively putting the finishing touches on its regulatory filings with health authorities to secure full approval for the drug next year.
Bancel described the milestone as a very, very happy moment for the scientific field and for patients eagerly awaiting new therapeutic options.
The mechanism behind the shot relies on a highly sophisticated approach: it is specifically designed to target the unique mutations present in each individual patient’s tumor, moving away from a traditional one-size-fits-all medical paradigm. The core concept trains the patient’s immune system to meticulously recognize and destroy those unique cancer markers, subsequently pairing that targeted cellular response with Keytruda, which acts to empower the body to attack the cancer more effectively.
For Moderna, the vaccine could provide a vital, additional commercial product in its expanding portfolio, diversifying its revenue streams following its widely known commercial vaccines targeting Covid-19, the flu, and respiratory syncytial virus.
Reinforcing the positive outlook from a financial perspective, analysts at UBS issued a research note on Thursday characterizing the data set as overall strong. They noted that the findings instill greater confidence in upcoming clinical studies evaluating the vaccine in kidney and bladder cancers. They echoed the sentiment that the negative stock movement was likely driven more by massive, unsustainable expectations than by any underlying disappointment in the data itself.
Against the backdrop of those extraordinary expectations, Moderna shares have experienced an immense run, spiking more than 530% year-to-date as of Thursday afternoon.
Meanwhile, shares of Merck, a significantly larger and more diversified pharmaceutical conglomerate, fell by about 1% on Thursday. Even with this slight dip, the company’s stock has enjoyed a strong performance, climbing nearly 41% over the course of the year.
Because the vaccine is entirely personalized to the genetic profile of each patient, the manufacturing process is intricate and can take up to six weeks to complete. However, Merck CEO Robert Davis told CNBC last week that the company firmly believes it can shorten that manufacturing timeline in the future, a development that would potentially allow the specialized shot to reach a much larger population of patients in a more timely manner.
