Novartis' 'Wild Card' Drug Scemblix Receives FDA Approval for Leukaemia Treatment

Novartis has achieved a significant milestone with the FDA approval of Scemblix (asciminib), a first-in-class STAMP inhibitor designed for patients with previously-treated chronic myeloid leukaemia (CML). This approval includes a conditional nod for Philadelphia chromosome-positive (Ph+) CML patients in the chronic phase who have undergone treatment with two or more tyrosine kinase inhibitors (TKIs), and a full approval for those with a T315I mutation.

In the pivotal ASCEMBL trial, Scemblix demonstrated a major molecular response (MMR) at 24 weeks in 25% of patients with Ph+ CML in the chronic phase, a significant improvement over the 13% MMR observed with Pfizer's Bosulif (bosutinib). This breakthrough offers a new therapeutic avenue for patients who have exhausted other treatment options.

Current CML treatments primarily rely on first-generation TKI imatinib (marketed as Glivec/Gleevec) and second-generation TKIs like Bosulif, Sprycel (dasatinib), and Tasigna (nilotinib). However, Scemblix's unique mechanism of action has the potential to overcome conventional TKI resistance and mitigate associated side effects, providing a crucial alternative for patients.

The full approval for T315I-positive CML was based on a non-randomised, open-label phase 1 trial involving 330 patients, which also explores combinations of Scemblix with other TKIs. According to Michael Mauro, an oncologist at Memorial Sloan Kettering Cancer Center (MSK), Scemblix addresses critical clinical challenges, especially for patients who have struggled with second-line treatments or developed the T315I mutation, which is associated with poorer outcomes.

Scemblix is poised to strengthen Novartis' CML portfolio, which continues to be a significant revenue driver. For instance, Tasigna generated $1.56 billion in sales in the first nine months of the year, and despite generic competition, Glivec remains a blockbuster, contributing approximately $250 million per quarter.

Looking ahead, Novartis is conducting a phase 3 study to evaluate Scemblix in previously-untreated patients, comparing it against investigator-selected TKIs. Results from this study are anticipated in 2024, with the hope that early intervention with Scemblix could lead to a treatment-free period for patients.

While Scemblix represents a significant advancement, not all of Novartis' high-risk projects have succeeded. For example, the company discontinued development of dry eye therapy ECF843 after it failed to meet endpoints in a phase 2b trial, underscoring the challenges inherent in drug development.