Watch and reassess in 6 to 12 months

Next review trigger: Any signal from the trigger watch list, or default review in 6 months.

Genetic validation is high. Chemistry challenge is the central risk. New GWAS evidence improves but does not resolve conviction. One or two near-term external readouts could shift the recommendation materially. Watch and reassess preserves optionality with low cost.

1. Insufficient isoform selectivity in clinic
2. Inadequate CNS exclusion
3. Magnitude of analgesia insufficient at safe doses

• Human GeneticsHigh

  SCN9A is among the most genetically validated peripheral pain targets in human biology.

• Disease BiologyHigh

  NaV1.7 is enriched in peripheral nociceptors; well-established role in pain signal initiation and propagation.

• Druggability and ModalityModerate

  Channel is druggable; isoform selectivity vs NaV1.5 (cardiac) and NaV1.4 (skeletal muscle) is the central chemistry challenge.

• Safety LiabilitiesModerate

  Anosmia in CIP carriers is the key on-target reference. CNS exclusion is required to preserve peripheral selectivity.

• Translational ModelsModerate

  Multiple rodent pain models available; species differences in NaV isoform pharmacology require careful study design.

• Competitive LandscapeModerate

  Multi-decade industry pursuit with multiple Phase II/III failures publicly reported. Several active programs at varying stages.