In rare diseases with multiple distinct pathogenic pathways, oral and injectable therapies targeting different mechanisms tend to converge on combination regimens rather than winner-take-all displacement. The oral formulation becomes the chronic daily backbone (favoured for lifelong tolerability), while injectable biologics are layered on top as adjuncts. This means each new injectable competitor approval can expand the oral drug's addressable market rather than cannibalising it — by legitimising the indication, expanding diagnosis rates, and creating combination-prescribing behaviour.
The oncology template is well-established (oral targeted therapies + IV monoclonal antibodies as standard-of-care combos). IgAN nephrology is the first non-oncology rare disease showing this dynamic, driven by KDIGO explicitly endorsing combination use of endothelin blockade with SGLT2 inhibitors and emerging evidence of BAFF/APRIL inhibitors layered on top of FILSPARI.
When a rare disease company faces incoming injectable biologic competition, do not automatically model market-share compression. First assess: (1) Do the mechanisms target distinct pathways? (2) Is the established drug oral vs. competitor injectable? (3) Is there early combination-use evidence? If all three hold, combination-therapy dynamics may apply — model a TAM expansion scenario alongside the share-compression scenario and weight by early clinical/prescriber signals. A company whose drug becomes the "backbone" of combination regimens has moat durability that a single-mechanism analysis will structurally underestimate.