From testing a patient's cancer to making their treatment

Testing a cancer's genes can help identify a drug that might work. It can also provide the information needed to make a treatment for that particular patient.

Intismeran autogene, being developed by Merck and Moderna, is an mRNA therapy designed around mutations specific to a patient's cancer. A phase 3 trial in people with high-risk melanoma that had been completely removed by surgery compared the addition of this individualized therapy with a control regimen. Both groups received pembrolizumab.

The treatment selects molecular targets from the mutations in the cancer. Taking the patient's HLA type into account, it encodes antigens in mRNA that their immune system is expected to recognize. Rather than giving the same drug to patients who share a mutation, this approach uses test results to determine the design of the drug itself. Technical account ↗

For this treatment to work as a business, a different product must be supplied for each patient within a dependable timeframe and to a consistent quality standard. Tumor and blood samples must be collected, their sequences analyzed, immune targets selected, and the treatment manufactured and delivered to the clinical site. The process has to be repeated for every new patient.

The arrangements needed to do this are already taking shape. In October, Tempus announced an expanded collaboration to handle the collection and transfer of tumor tissue and blood samples and, subject to the necessary regulatory approvals, to provide sequencing services. A diagnostic company is taking on part of the process of making a patient's treatment. Tempus announcement ↗

Clinical results are also emerging. In the phase 3 trial, the estimated proportion of patients alive without a recurrence at two years was 82.2% with intismeran plus pembrolizumab, compared with 70.0% in the control group. The disease and treatment setting are specific, but the result shows that designing and manufacturing a treatment for each patient can deliver a clinical benefit. Overall survival data are not yet mature. Joint Merck–Moderna announcement ↗

What accumulates here is more than knowledge of a single effective sequence. It is experience in selecting targets for individual patients, supplying their treatments, and evaluating the clinical results. Examining which outcomes occurred in which patients, alongside the overall trial results, could inform improvements in target selection and treatment design. The comparison does not, however, establish the performance of the target-selection algorithm in isolation.

Sustaining this supply requires more than efficacy. Turnaround time, manufacturing success rates, and the cost per patient also matter. Reaching phase 3 shows that there is an operational system capable of running this process, at least under clinical-trial conditions. Pricing and the scale of uptake after any approval remain unknown. If the treatment is approved, the question will be at what scale and cost that system can be maintained.

Individualization in this treatment does not stop at choosing a drug: it extends to making and delivering each patient's supply. Looking at it as a concrete business makes the necessary technology, supply arrangements, and priorities for improvement easier to identify.