Enliven Highlights Early Results for Leukemia Drug Targeting Novartis' Scemblix

Enliven Therapeutics has announced promising new Phase 1 data for its chronic myeloid leukemia (CML) treatment, ELVN-001, which it hopes will compete with Novartis’ Scemblix. The experimental therapy was tested in 39 patients at various dosage levels, with 18 patients meeting the criteria for efficacy evaluation at the cutoff point. According to Enliven, 44% of these patients experienced a “cumulative major molecular response” (MMR) after 24 weeks. This response rate was consistent among patients who had previously shown resistance to tyrosine kinase inhibitors (TKIs) and those who had been treated with Scemblix.

Although this is a preliminary observation, it suggests that ELVN-001 could potentially offer more treatment options for CML patients if these positive responses continue. CML is notably difficult to treat due to its chronic nature. Novartis estimates that up to 50% of patients do not achieve their MMR goals and up to 25% switch TKIs within the first year of treatment.

The patient group in the Enliven study exemplified these challenges: 27 out of 39 patients had undergone treatment with at least three prior TKIs, and 10 had been treated with at least five. Furthermore, 21 patients had previously taken Scemblix, and 27 had discontinued their most recent TKI due to lack of efficacy.

Scemblix, approved in 2021, was the first third-generation therapy available for CML patients, targeting the same mutation as ELVN-001. Novartis CEO Vas Narasimhan has described Scemblix as a “wild card” drug, indicating its high-risk, high-reward potential.

Mizuho analyst Salim Syed commented that Enliven’s results represent a significant achievement for the company. He noted that the 44% MMR after 24 weeks was consistent with previous findings from a 12-week interval earlier in the year. Importantly, no cardiovascular toxicity was observed, which Syed described as a crucial aspect since heart-related side effects typically begin to appear after 24 weeks in patients taking TKIs.

Phil Nadeau, an analyst at TD Cowen, observed that ELVN-001’s MMR is competitive with Phase 1 data from other recently approved CML drugs, such as Scemblix (which showed a 37% MMR at 24 weeks) and Pfizer’s Bosulif (which demonstrated a 15% MMR at 28.5 months). He did caution, however, about the limitations of comparing results across different clinical trials.

ELVN-001 is a small molecule kinase inhibitor designed to target the BCR-ABL gene fusion, a significant driver of CML. Enliven claims that the drug can also counter one of the most common gene mutations, T315I, which often arises in patients taking TKI drugs for CML treatment.

Further data from the study are anticipated next year, with follow-up results expected from 60 to 100 patients. Enliven has also indicated that it is considering a head-to-head trial.

Note: An earlier version of this article incorrectly stated that Enliven expected to have its head-to-head trial approved by the FDA by the end of next year. The company is still in the planning stages for this trial.

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