Page 60 - Binder2

of studies, registries, and industry reports—none of which
have the authority or consistency to challenge the status
quo.

This gap creates a dangerous illusion: that tolerization is
rare, anecdotal, or manageable. In reality, it's simply
underreported and undermeasured. For instance, studies
have shown that the formation rates of anti-drug antibodies
(ADAs) vary significantly, with some biologics like
Remicade exhibiting ADA rates as high as 65.3% in certain
studies, while others report rates as low as 0%.

Such variability often stems from differences in assay
sensitivity and detection methods, leading to inconsistent
reporting. Without standardized monitoring and regulatory
mandates to prioritize immune tolerance, drug developers
have little incentive to engineer for it, perpetuating a cycle
where the long-term sustainability of biologic therapies
remains an afterthought.

But the FDA released a new draft guidance to standardize
how immunogenicity in response to ADAs is described in
product labels in 2024. This guidance says that companies
should describe relevant ADAs as well as quantifying their
incidence.

Great in theory, but the issue is this guidance is based upon
data collected in clinical trials, not post market
surveillance. A measure taken to increase the visibility of
the effects of ADAs further clouds the reality of the
situation.

And so, tolerization stays hidden—not because it isn’t
happening, but because the system isn’t designed to catch
it before launch.

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