===
-- Phase III ASC4FIRST trial met both primary endpoints with clinically
meaningful and statistically significant results; Scemblix(R) (asciminib)
demonstrated superior 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%)1

-- 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 discontinuation1
-- TKIs have transformed CML treatment, but unmet need remains; many newly
diagnosed patients do not meet molecular response goals, and many
discontinue or change treatment due to intolerance2-17

-- Scemblix was granted US FDA Breakthrough Therapy Designation, submission
is now in review under the agency's Oncology Center of Excellence RTOR
program; data will be presented as a plenary at EHA and today as a
late-breaking abstract at ASCO
===
Basel, May 31, 2024 -- Novartis today presents positive results from the pivotal Phase III ASC4FIRST trial as a late-breaking abstract at the 2024 American Society of Clinical Oncology (ASCO) meeting. Scemblix(R) (asciminib) demonstrated superior major molecular response (MMR) rates at week 48 compared to investigator-selected standard-of-care (SoC) tyrosine kinase inhibitors (TKIs) imatinib, nilotinib, dasatinib and bosutinib, and compared to imatinib alone in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP)(1) . Scemblix also showed a numerical improvement in MMR at week 48 vs. second generation (2G) TKIs (nilotinib, dasatinib and bosutinib)(1) . Additionally, Scemblix demonstrated a favorable safety and tolerability profile, with fewer adverse events (AEs) and treatment discontinuations vs. both imatinib and 2G TKIs(1) .

"Scemblix is the first CML treatment to show significantly better efficacy compared to investigator-selected standard-of-care TKIs," said Prof. Tim Hughes, MD, South Australian Health & Medical Research Institute (SAHMRI). "When you combine superior response with the excellent safety and tolerability profile of Scemblix, we have a very promising potential frontline option for newly diagnosed patients to support them in achieving their treatment goals."

The median follow-up was 16.3 and 15.7 months for Scemblix and investigator-selected SoC TKIs, respectively(1) . Nearly 20% more patients treated with Scemblix achieved MMR at week 48 vs. investigator-selected SoC TKIs and nearly 30% more patients achieved MMR at week 48 vs. imatinib alone(1) . Patients treated with Scemblix also achieved deeper rates of molecular responses (MR4 and MR4.5) compared with investigator-selected SoC TKIs and imatinib alone(1) .

===

Overall(a)           Imatinib stratum(b)     2G TKI stratum(c) 
Scemblix (n=201)          Scemblix (n=101)     Scemblix (n=100) vs. 
vs. investigator-selected   vs. imatinib (n=102)     2G TKIs (n=102) 

SoC TKIs (n=204)

-----------------------  ----------------  --------------------------  ---------------------  --------------------- 
Week 48 MMR          67.7% vs. 49.0%           69.3% vs. 40.2%               -- 
Primary endpoints          rates 
-----------------------  ----------------  --------------------------  ---------------------  --------------------- 
Week 48 MMR               18.9%                     29.6% 
Treatment             (9.6%--28.2%)            (16.9%--42.2%)               -- 

difference (95%
CI)
----------------------- ---------------- -------------------------- --------------------- ---------------------
Adjusted 1-sided <.001 <.001 -- p-value

-----------------------  ----------------  --------------------------  ---------------------  --------------------- 
Week 48 MMR                 --                       --               66.0% vs. 57.8% 
Secondary endpoints(d)       rates 
-----------------------  ----------------  --------------------------  ---------------------  --------------------- 
Week 48 MR4            39% vs. 21%               43% vs. 15%            35% vs. 26% 
-----------------------  ----------------  --------------------------  ---------------------  --------------------- 
Week 48 MR4.5            17% vs. 9%               18% vs. 5%             16% vs. 13% 
-----------------------  ----------------  --------------------------  ---------------------  --------------------- 

(a) All patients receiving Scemblix (n=201) or investigator-selected
SoC TKIs (n=204). Treatment difference after adjusting
for pre-randomization selected TKI and EUTOS long-term
survival (ELTS) risk groups at baseline.
(b) The 203 patients within the pre-randomization-selected
imatinib stratum were randomized to receive either
Scemblix (n=101) or imatinib (n=102). Treatment difference
after adjusting for ELTS risk groups at baseline.
(c) The 202 patients within the pre-randomization
selected 2G TKIs stratum were randomized to receive
either Scemblix (n=100) or 2G TKIs (n=102: nilotinib,
48%; dasatinib, 41%; bosutinib, 11%).
(d) Secondary endpoints were not powered for statistical
significance.

===
In newly diagnosed patients, the safety profile was consistent with previous registration studies with no new safety concerns observed(1) . Fewer grade >=3 AEs, dose adjustments to manage AEs, and half the rate of AEs leading to treatment discontinuation were reported for Scemblix vs. both imatinib and 2G TKIs(1) .

===

Scemblix  Imatinib  2G TKIs 
-------------------------------------------------  --------  --------  ------- 
Grade >=3 AEs(a)                        38%       44%      55% 
-------------------------------------------------  --------  --------  ------- 
AEs leading to treatment discontinuation(a)           5%       11%      10% 
-------------------------------------------------  --------  --------  ------- 
AEs leading to dose adjustments/ interruptions(a)       30%       39%      53% 
-------------------------------------------------  --------  --------  ------- 

(a) In patients who experienced >=1 adverse event.

===
"Patients living with CML need efficacious and well-tolerated treatment options that help them achieve meaningful outcomes as they manage their chronic condition," said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. "The compelling ASC4FIRST data highlight the potential of Scemblix to achieve better results than standard-of-care in newly diagnosed adults, while maintaining a favorable safety and tolerability profile. These results reinforce Scemblix as a proven treatment in Ph+CML-CP, as we continue to build on our 20-year legacy in CML innovation."

CML is a chronic condition and the side effects of standard-of-care can be challenging for patients. They often affect their daily life and can lead to high rates of treatment switching," said Gerald Clements, CML caregiver, patient advocate and Steering Committee Treasurer at CML Advocates Network. "Effective care that can be tolerated long-term is a key unmet need. By potentially bringing Scemblix to patients when they are first diagnosed, they may have an opportunity to be on a highly effective treatment while also maintaining their day-to-day from the start."

The trial remains ongoing, with the next scheduled analysis at week 96 to evaluate the key secondary endpoint (MMR at week 96) and additional secondary endpoints(18) .

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

About ASC4FIRST Phase III Clinical Trial

ASC4FIRST (NCT04971226) is a Phase III, head-to-head, multi-center, open-label, randomized study of oral Scemblix(R) 80 mg QD vs. investigator-selected first- or second-generation TKIs (imatinib, nilotinib, dasatinib or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP(18) . The two primary endpoints of the study are to compare efficacy of asciminib vs. investigator-selected SoC TKIs and to compare efficacy vs. that of TKI within the stratum of participants with imatinib as pre-randomization selected TKI, based on proportion of patients that achieve MMR at week 48(18) .

The study remains ongoing with key secondary endpoints of proportion of patients that achieve MMR at week 96 and a safety endpoint of discontinuation of study treatment due to an AE (TTDAE) by week 96(18) . The study also assesses additional secondary safety and efficacy endpoints, including MMR, MR4, MR4.5, complete hematological response (CHR) and BCR::ABL1 <=1% at and by all scheduled data collection time points; duration of and time to first MMR, MR4 and MR4.5; time to treatment failure; event-free survival, failure-free survival, progression-free survival and overall survival(18) .

About Scemblix(R) (asciminib)

Scemblix(R) is the first CML treatment that works by Specifically Targeting the ABL Myristoyl Pocket (referred to as a STAMP inhibitor in scientific literature)(19-21) . The current approved CML treatments are TKIs that target the ATP-binding site (ATP-competitive) (21) .

(MORE TO FOLLOW) Dow Jones Newswires

May 31, 2024 08:00 ET (12:00 GMT)