Enliven announces updated data from ELVN-001 trial

Enliven (ELVN) announced updated data from the Phase 1 ENABLE clinical trial evaluating ELVN-001 in patients with chronic myeloid leukemia in an oral presentation at the European Hematology Association Congress taking place June 12-15 in Milan, Italy, and virtually. As of the cutoff date of April 28, 90 patients have been enrolled in the ongoing Phase 1 trial across dose levels ranging from 10 mg once a day (QD) to 80 mg twice a day. The vast majority of patients remain on study with a median treatment duration of ~29 weeks. Patients enrolled were heavily pretreated: 67% of patients received three or more unique prior TKIs, including 58% of patients who received prior asciminib and 43% of patients who received prior ponatinib. 72% of patients had discontinued their prior TKI due to lack of efficacy. Of the enrolled patients, 53 with typical BCR::ABL1 transcripts and without T315I mutations were evaluable for major molecular response by 24 weeks. 25 of 53 evaluable patients were in MMR by 24 weeks, with 13 of 41 achieving and 12 of 12 maintaining MMR. Of those resistant to their last TKI, 14 of 34 were in MMR by 24 weeks. Of those previously treated with asciminib or ponatinib, 12 of 34 were in MMR by 24 weeks. All patients who achieved or maintained MMR were still in MMR at the time of data cutoff. These data continued to compare favorably to precedent Phase 1 MMRs for approved BCR::ABL1 TKIs, particularly given the more heavily pretreated patient population in the ELVN-001 clinical trial. Specifically, the achieved MMR rate by 24 weeks of 32% compares favorably with historical data from less heavily pretreated patients receiving asciminib, which showed achieved MMR rates of 24% in the Phase 1 trial and 25% in the ASCEMBL Phase 3 trial. ELVN-001 remains well-tolerated across all evaluated doses. Only 3.4% of patients had dose reductions due to treatment-emergent adverse events and 4.6% of patients discontinued due to TEAEs. The majority of TEAEs were low frequency and low grade, and the hematologic TEAE profile was similar to or better than the approved TKIs. Only 2.3% of patients experienced greater than or equal to Grade 3 non-hematologic treatment-related AEs. No evidence to date of enhanced cardiovascular toxicity and no treatment-related arterial occlusive events. The maximum tolerated dose was not reached, and no exposure-toxicity relationship was observed. The PK profile supports once-daily dosing with flexible administration requirements, including the ability to take with or without food. There is low potential for drug-drug interactions, an important advantage given that the average CML patient takes approximately five concurrent medications.