SCEMBLIX (asciminib) is the first FDA-approved CML treatment that binds to the ABL myristoyl pocket. In October 2021, the FDA granted accelerated approval to SCEMBLIX for patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase, previously treated with two or more tyrosine kinase inhibitors, and approved asciminib for adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase with the T315I mutation.

The ASC4FIRST Phase III study (NCT04971226) evaluates SCEMBLIX as a first-line treatment in CML. As per Novartis Q1 2024, earnings call transcript, primary endpoints were met versus all standard of care TKI and -- versus GLEEVEC as well, favorable safety and tolerability profile. 

On 31st May 2024, Novartis shared the full data from the ASC4FIRST study at the ASCO 2024 meeting. The data was as follows: 

• Phase III ASC4FIRST trial met both primary endpoints with clinically meaningful and statistically significant results

• SCEMBLIX (asciminib) demonstrated superior major molecular response (MMR) rates at week 48 vs. investigator-selected SoC TKIs (imatinib, nilotinib, dasatinib, and bosutinib) (67.7% vs. 49.0%) and imatinib alone (69.3% vs. 40.2%)

• The MR4 rates at week 48 were 38.8% vs. 20.6%, respectively, and the 48-week MR4.5 rates were 16.9% vs. 8.8%, respectively.

• In the imatinib stratums, the MR4 rates were 42.6% in the asciminib arm (n = 101) and 17.8% in the TKI arm (n = 102); the MR4.5 rates were 17.8% and 4.9%, respectively. In the second-generation TKI stratum, the MR4 rates were 35.0% and 26.5% in the investigational (n = 100) and control (n = 102) arms, respectively; the MR4.5 rates were 16.0% and 12.8%, respectively.

• SCEMBLIX also demonstrated a favorable safety and tolerability profile vs. imatinib and 2G TKIs, with fewer grade ≥3 AEs, dose adjustments, and half the rate of AEs leading to treatment discontinuation. 

These results have been submitted to the US FDA via the Oncology Center of Excellence Real-Time Oncology Review (RTOR) program and SCEMBLIX has been granted Breakthrough Therapy Designation. The data will also be presented as a plenary at the European Hematology Association (EHA) 2024 Congress in June.

KOL insights

“Taken together, these results suggest that, for the first time, a more potent TKI demonstrates superior efficacy without sacrificing tolerability and safety compared to all available TKIs” – Expert Opinion.

“Asciminib is the only agent to show a statistically significant superior efficacy and excellent safety and tolerability vs all current standard-of-care frontline treatments, with the potential to be the therapy of choice for CML”– Expert Opinion.

Conclusion

SCEMBLIX saw an 83% growth in Q1 2024, primarily driven by its third-line indication. With the first-line submission on track to be completed in the coming months based on the ASC4FIRST Phase III study, the product is expected to continue experiencing strong demand.

The primary endpoint of the ASC4FIRST study was the major molecular response (MMR), making it intriguing to see how SCEMBLIX performs in this regard. One exciting aspect of SCEMBLIX is its long exclusivity period, and because it targets a rare disease, it is not subject to negotiations with the IRA. This positions Novartis to experience growth with SCEMBLIX throughout this decade and well into the next, both in the US and globally.

To conclude, SCEMBLIX demonstrated a statistically superior response in terms of MMR at 48 weeks, both against imatinib and against all TKIs, and a safety and tolerability profile that favors asciminib against all of the TKIs, suggesting that this strong benefit-risk profile may change the treatment paradigm in CML.