molecules of the month

Upcycling a γ-secretase inhibitor for a potentially first- & best-in-class treatment for aggressive desmoid tumors. Nirogacestat was recently granted FDA priority review for rare, aggressive, locally invasive, soft-tissue desmoid tumors (DTs). This reversible, non-competitive gamma secretase inhibitor (GSI) draws its anticancer activity from its ability to block Notch signaling, and is the lead drug from a 2017 Pfizer spinout, SpringWorks Therapeutics. While not metastatic or life-threatening, desmoid tumors can compress vital organs, causing nerve damage, severe pain and intestinal complications, and there are no FDA-approved treatments. Therapeutic approaches for DT include robust chemotherapy, radiation and TKI treatments, but these are often poorly tolerated and inconsistently efficacious. For these reasons, nirogacestat has been granted Fast Track, Breakthrough Therapy and Orphan Drug…