Moderna shares went tumbling as a third tier oncology website revealed the hazard ratio of the moderna cancer therapeutic vaccine breaking the Esmo embargo.
The hazard ratio was exactly what you would get if you give pembro before surgery instead of after (as the moderna merck trial does). The obvious speculation is the vaccine— incredibly costly and bespoke— and the tumor still in the body—do the same thing immunologically. Will the vaccine still work if you give it in a neo adjuvant trial? Only another trial will answer that.
And does this strategy work in other tumors which are not immunologically unique like melanoma and RCC? Many trials will tell us.
The rollercoaster ride of Moderna stock since the press release topline result reflects a bizarre system where commercially and medically important information is given out in tiny doses.
First, the press release to make the SEC happy.
Then the hazard ratio and curves to make the conference and professional societies happy. (Sorry embargo)
Then a little more data about the study so you can actually critically appraise it to make the journals happy.
Then a lot more data about the study to make the FDA happy, a fraction of this data ultimately makes it to the medical review, and package label. All of his data is necessary to properly critically appraise.
Then back to condensing the material to a tiny leaflet to market to doctors and patients.
Then a television ad.
Then a card to put in a bag and hang on your door at asco next year.
Then a 1 second blurb to tell doctors.
Then turning it into a boards question, and forcing doctors in training to blindly parrot: if you're doing adjuvant pembro you must also add… moderna vax. #not sponsored
A curious observer might ask if any of this has to do with the best interest of patients. It's difficult to see that. Instead, the process is optimized to trickle out information in a way that the reaction can be controlled and manipulated. Critics are inherently at a disadvantage as press releases and abstracts only showcase the positive side of the product and not the negatives. I still have no idea what the side effects were. I still have no idea how many patients were censored, lost to follow-up, did not complete therapy etc.
In this case It is likely that leaking the information sabotaged the carefully orchestrated narrative around the product. The same hazard ratio delivered a couple days later with a choreographed standing ovation may have resulted in a different short-term outcome.
Because one bespoke mRNA vaccine works in one immunologically interesting tumor after surgical removal does not mean
1 It will work if pembro is giving neo adjuvant
2 It will work in other tumors
3 It will work in the metastatic setting
4 Any sweeping lesson about mRNA shots used for infectious diseases
It does mean ironically that
Cancer therapeutic mRNA vaccines are financially lucrative, and have plenty of market incentives, and do not require further federal support.
Your neoadjuvant speculation is the sharpest line in this post — the hazard ratio being “exactly what you would get if you give pembro before surgery instead of after” reframes the vaccine not as a breakthrough but as possibly redundant immune priming. But here's a variable I'd want in the data trickle that even the journals may never deliver: how many randomized patients ever received the full bespoke course? A personalized neoantigen vaccine has to be manufactured per patient — sequencing, synthesis, QC — and patients can progress, withdraw, or run out of time between biopsy and dosing. Manufacturing failures and dropouts before the first dose all sit inside the intention-to-treat effect being reported.
You wrote that you still don't know “how many patients were censored, lost to follow-up, did not complete therapy etc.” — I'd add: did they not complete because of toxicity, or because the product was never made in time? If it's the latter, the leak tells us nothing about whether the biology works.
Dr. Prasad is right to insist that a promising clinical result is not a license for sweeping claims. The Phase 3 trial provides strong evidence that adding an individualized mRNA vaccine to post-operative pembrolizumab improves recurrence-free and distant-metastasis-free survival in patients with resected high-risk melanoma. The similarity in hazard ratios to those reported for pembrolizumab before surgery followed by additional pembrolizumab after surgery is striking, but it may be coincidental. Still, it makes one pause to ask: Why do we need the vaccine if we can get equivalent results without it? Identical hazard ratios from different trials do not establish equivalent treatments, much less prove that the vaccine contributed nothing. The comparison raises a question; it does not answer it. The trial does not establish longer overall survival, efficacy in other cancers or metastatic disease, or a general lesson about mRNA vaccines. Dr. Prasad is also right that topline announcements and staged disclosures make independent appraisal difficult.
Dr. Prasad is less persuasive when he moves from justified skepticism to conclusions that are not well supported. Calling the vaccine “incredibly costly” requires evidence about actual manufacturing costs and eventual pricing. We can make assumptions, but we don’t really know. Declaring the technology financially lucrative likewise goes beyond what we know. Commercial potential and demonstrated profitability are two different things. It is tempting to argue that the success of an industry-funded trial obviates the need for further federal support for cancer research, but one successful trial cannot establish that conclusion. Industry and federal funding need not serve the same purposes. Dr. Prasad’s claims may prove right, but so far, I’m not convinced. The irony is that his strongest point supplies the standard by which his own conclusions should be judged: do not extrapolate beyond the evidence. The result of this trial is neither proof that the mRNA cancer-vaccine revolution has arrived nor evidence that the vaccine is merely pre-surgery Keytruda in disguise. The trial appears to represent a meaningful advance in one defined setting, with important questions still unanswered. Skepticism should keep the claims within those boundaries, not move the goalposts in the opposite direction.