Moderna (MRNA) desperately needs to find new ways to make money, especially with coronavirus vaccine revenue expected to fall off a cliff in the next few years. It thinks cancer vaccines could be one solution.
The mRNA pioneer and Merck (MRK) announced promising preliminary results from a study evaluating a cancer vaccine candidate combined with blockbuster immunotherapy Keytruda in individuals with advanced melanoma. The combination treatment reduced the risk of recurrence or death by 44% compared to Keytruda alone.
Make no mistake: This provides hope for a significant advance in cancer treatment. But only in a certain kind of treatment setting.
There are important nuances for investors to consider. For example, no one enrolled in the study had cancer when the clinical trial started. Digging deeper into the data, study design, and competitive landscape provide a clearer picture of how future mRNA cancer vaccines will and won't be used -- at least with existing tools.
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Those Devilish Details
The companies enrolled 157 individuals who previously had stage 3 or stage 4 melanoma, commonly referred to as advanced melanoma, and had their tumors surgically removed. Individuals were randomized into two treatment groups and tracked for up to 54 weeks.
- One group of patients received the anti-PD-1 immunotherapy Keytruda, which helps the immune system find cancer cells more easily. Individuals received up to 18 cycles of immunotherapy, with each cycle taking three weeks.
- One group of patients received a combination treatment of Keytruda and a personalized mRNA vaccine candidate called mRNA-4157/V940. Individuals received nine doses of the mRNA vaccine candidate and up to 18 cycles of immunotherapy.
Moderna designed personalized vaccine candidates for each patient using tumor samples collected from a prior biopsy. Scientists encoded an mRNA sequence with up to 34 neoantigens produced by each individual tumor. These neoantigens would help train an individual's immune system to seek out and destroy cancer cells.
At the 54-week timepoint in the study, Moderna and Merck found the combination treatment reduced the risk of recurrence or death by 44% compared to using Keytruda alone.
Time for those devilish details.
- To be eligible for the study, individuals were required to be cancer free. No one in the study had cancer when the clinical trial started. This is why recurrence-free survival (RFS) was used as the primary endpoint instead of more common measures such as progression-free survival (PFS) or overall survival (OS).
- All individuals previously had advanced melanoma that was completely removed with surgery. This is not a very common patient population in melanoma or in other solid tumor cancers. Most advanced tumors cannot be surgically removed.
- Reducing the risk of recurrence or death by 44% compared to Keytruda alone sounds impressive, but Keytruda itself is not very effective as a monotherapy in advanced melanoma. Merck's previous clinical trials evaluating the immunotherapy in advanced melanoma achieved a median PFS of 4.1 months, although these individuals had cancer during the study.
In other words, the preliminary results for the mRNA vaccine candidate are promising, but for specific reasons and in specific treatment settings.
The results do not suggest mRNA vaccines will be used to treat individuals who have cancer. Instead, this emerging class of medicines could be used to help individuals who achieve remission remain in remission longer compared to currently available options. That's still valuable, but it's important to acknowledge the difference.
Could mRNA vaccines ever be used to directly treat cancer? Perhaps, but clinical trial results to date have been underwhelming.
Fellow mRNA pioneer and pandemic star BioNTech (BNTX) conducted a clinical trial evaluating an mRNA cancer vaccine, BNT111, in combination with an anti-PD-1 immunotherapy in patients with advanced melanoma. Unlike the study from Moderna and Merck, the individuals in this clinical trial had advanced melanoma during the study.
BioNTech found the combination treatment achieved a partial response rate of 35%, meaning roughly one-third of individuals saw tumor volumes shrink by at least 30%. However, in a separate clinical trial in advanced melanoma, Keytruda alone achieved a partial response rate of 27%. That suggests mRNA cancer vaccines may not provide much benefit in directly treating cancer.
A Breakthrough, but of a Different Kind
The media isn't always a shining beacon for science communication. That can lead to a misunderstanding, and sometimes distrust, of science among the public.
Yes, personalized mRNA vaccines could be used one day as a cancer treatment, but primarily as a follow-up cancer treatment for individuals who have already cleared their tumors with prior therapy. All available data collected to date suggest mRNA vaccines will provide little benefit in directly treating solid-tumor cancers.
That could change with advances in technology and our understanding of biology, but it's still early.
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