Initially '788 will have little overlap with osimertinib, about 5-6% representing compound T790M mutations. Beyond T790M, other Exon 20 mutations in both EGFR and Her2, are not currently effectively inhibited by other TKIs, approved or otherwise. Ariad will likely propose a diagnostic test for Exon 20 mutations to identify patients, so if you test positive you are eligible, regardless of presence of other EGFR or Her2 mutations, or line of therapy.
Of course it doesn't hurt that '788 is 10 times more potent against EGFR mutations than erlotinib or gefitinib, and has "less than 1 picomolar" IC50s against certain EGFR and Her2 mutations beyond Exon 20, at least according to the patent. So eventually I expect trials for use of '788 in broader, albeit more competitive, EGFR populations. This broader profile is critical for resistant populations, and '788's use as monotherapy. But the initial, and fastest, path to approval will be through the unmet need of Exon 20 mutations. So 25,000 patients first, with potential to compete for the other ~75,000 later. |
