Texas MPN Workshop 2021 | Avapritinib FDA approval for advanced systemic mastocytosis

Avapritinib is an extremely selective and potent inhibitor of mutant KIT, specifically the D816 mutation, usually D816V mutation in exon 17, that drives about 95% of cases of systemic mastocytosis across the board. So, it’s very potent and selective for this particular mutation. Much more selective for the mutant than say for wild-type KIT. So, it got approved in the US on the 16th of June 2021 for advanced systemic mastocytosis, which is generally comprised of aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and also mast cell leukemia. The approval was based on data from the Explorer and Pathfinder studies. These were Phase I and Phase II trials respectively of avapritinib in advanced SM.

The response rates were very high, 75% by the modified International Working Group criteria, which is really striking. Responses were very quick as well, median eight weeks or two months. They were durable and they importantly deepened over time, so they got better over time. Your clinical improvements turned into partial responses and your partial responses turned into complete responses, so that is really important. Median survival in the EXPLORER study, the Phase I study that has a longer follow-up was about 46.9 months, again, very robust. And this was really driven by the SMA 10 patients. There were fewer patients, as you can imagine with mast cell leukemia and aggressive SM and the median survivals for those have not been reached. The PATHFINDER study is a newer study and has shorter follow-up, so the median survivals have not been reached on that one as of yet, it only has about 10 months of a median follow-up. EXPLORER is much longer.