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• Was this risk disclosed adequately during
clinical trials?
Trials are typically short-term—designed to show
response, not durability. Long-term immunogenicity
data is limited, and ADA testing is often buried in
appendices or underpowered subgroup analyses.
• Is the pricing still justified if the product can’t
sustain its benefit?
A $100,000 biologic that only works for a year
before the body rejects it is not just a poor value—
it’s an ethical and economic red flag.
• Why isn’t there a more robust immunology-
informed development strategy?
If tolerization is predictable—and often
preventable—why aren’t more biologics engineered
to coexist with the immune system from the start?

Rather than engage these questions head-on, many
companies lean on euphemism. Tolerization gets recoded
as “secondary non-response,” “waning efficacy,” or
“treatment cycling.” These terms are softer, vaguer, and
easier to fold into the background noise of chronic disease
management. They suggest variability, not failure. Patient
idiosyncrasy, not design flaw.

This linguistic sleight of hand helps preserve the
narrative—that biologics are durable, precise, and worth
the price. And by extension, it helps preserve the margin.
Because once tolerization enters the spotlight, pricing
models, regulatory frameworks, and investor expectations
all come under pressure.

And so, it stays in the shadows—not because it’s rare, but
because it’s profitable to ignore.
But the longer it’s ignored, the more fragile that narrative
becomes.

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