Scemblix® (asciminib) continues to show superior efficacy with more-than-two-fold improvement in major molecular response rate vs. Bosulif®* (bosutinib) at 96 weeks (37.6% vs. 15.8%), building on 24-week results1,2
Long-term safety remains consistent, with discontinuation rates due to adverse events more than three times lower in the Scemblix vs. Bosulif arm (7.7% vs. 26.3%)1,2
Updated results continue to support the use of Scemblix in patients with Philadelphia chromosome-positive CML in chronic phase previously treated with two or more TKIs, and its potential to transform the standard of care with a differentiated mechanism of action1,2
Clinical development program continues, evaluating Scemblix across multiple lines of treatment in CML, with additional data being presented at the European Hematology Association 2022 Hybrid Congress
EAST HANOVER, N.J., June 7, 2022 -- Novartis today announced longer-term follow-up data from the Phase III ASCEMBL trial for patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) previously treated with two or more tyrosine kinase inhibitors (TKIs), presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. In this analysis, the proportion of patients in the Scemblix® (asciminib) arm (n=157) who achieved a major molecular response (MMR) at 96 weeks was more than double that in the Bosulif®* (bosutinib) arm (n=76) (37.6% vs. 15.8% [P=.001]), substantially increasing from previous analyses1,2. Additionally, the probability of maintaining MMR for at least 72 weeks for patients treated with Scemblix was 96.7% (95% CI, 87.4%–99.2%), reflecting long-term durability of efficacy1.
Despite longer duration of exposure for patients in the Scemblix arm – with a median of 23.7 months vs. 7.0 months for patients in the Bosulif arm – the updated 96-week analysis showed the proportion of patients treated with Scemblix who discontinued treatment due to adverse events (AEs) continued to be more than three times lower than those treated with Bosulif (7.7% vs. 26.3%). No new on-treatment deaths were reported since the primary analysis at 24 weeks1,2.
"In a chronic cancer where resistance can develop to many of the existing therapies, or where patients can have their quality of life negatively impacted by treatment side effects over time, it's encouraging to see sustained and increasing efficacy with consistent adequate tolerability for patients treated with Scemblix in the longer term," said Jorge E. Cortes, MD, Director, Georgia Cancer Center, Augusta University. "This 96-week data shows the potential of Scemblix and its unique mechanism of action to help change the treatment paradigm in CML."
Scemblix is the first FDA-approved CML treatment that works by binding to the ABL myristoyl pocket3. With this novel mechanism of action, it is also known in scientific literature as STAMP inhibitor, Scemblix can help address resistance to TKI therapy in patients with Ph+ CML-CP and overcome mutations at the defective BCR-ABL1 gene, which is associated with the over-production of leukemic cells2,4-10. Scemblix continues to be studied across multiple lines of treatment for CML-CP11-18.
In addition to durable responses consistent with the primary analysis, more patients treated with Scemblix than Bosulif had BCR::ABL1≤1% (45.1% vs 19.4%) at 96 weeks. The most frequent (>10% in any treatment arm) grade ≥3 AEs on Scemblix vs. Bosulif, respectively, were thrombocytopenia (22.4%, 9.2%), neutropenia (18.6%, 14.5%), diarrhea (0%, 10.5%), and increased alanine aminotransferase (0.6%, 14.5%)1. The values for these AEs were similar to the values reported at the 24 and 48 week analyses1,2,19.
"These longer-term results offer a more robust view of the promising potential of Scemblix, and will help support ongoing regulatory filings as we seek to bring this therapy to more patients across the globe," said Jeff Legos, Executive Vice President, Global Head of Oncology & Hematology Development, Novartis. "As leaders in CML treatment innovation, we believe that with Scemblix, we have the potential to once again transform the standard of care for people affected by this disease."
Scemblix (asciminib) is FDA-approved for the treatment of adult patients with Ph+ CML-CP pre-treated with two or more TKIs, as well as adult patients with Ph+ CML-CP with the T315I mutation. The first indication is approved under the US FDA Accelerated Approval Program based on MMR rate at 24 weeks; continued approval for the first indication may be contingent upon verification and description of clinical benefit from confirmatory evidence3.
Scemblix represents an important development for patients who experience resistance and/or intolerance to currently available TKI therapies, and it is being studied across multiple treatment lines for CML-CP, both as monotherapy and in combination2,11-18. Specifically, the ASC4FIRST Phase III study (NCT04971226) evaluates Scemblix in newly-diagnosed adult patients with Ph+ CML-CP vs. an investigator-selected TKI, with recruitment proceeding ahead of plan12.
Regulatory reviews for Scemblix in multiple countries and regions across the globe are ongoing. These updated 96-week ASCEMBL results are being shared with regulatory authorities, as we seek to bring Scemblix to more patients in more countries across the globe.
About Novartis Commitment to CML
Novartis has a long-standing scientific commitment to patients living with CML. For more than 20 years, our bold science has helped transform CML into a chronic disease for many patients. Despite these advancements, we're not standing still. We continue to research ways to target the disease, seeking to address the challenges with treatment resistance and/or intolerance that many patients face. Novartis also continues to reimagine CML care through its commitment to sustainable access for patients and collaboration with the global CML community.
SCEMBLIX® (asciminib) tablets is a prescription medicine used to treat adults with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with 2 or more tyrosine kinase inhibitor (TKI) medicines. The effectiveness of SCEMBLIX in these patients is based on a study that measured major molecular response (MMR) rates. No clinical information is available to show if these patients treated with SCEMBLIX live longer or if their symptoms improve. Ongoing studies exist to find out how SCEMBLIX works over a longer period of time.
SCEMBLIX is also approved for use in adults with Ph+ CML in CP with the T315I mutation.
It is not known if SCEMBLIX is safe and effective in children.
Important Safety Information
SCEMBLIX® (asciminib) tablets may cause low platelet counts (thrombocytopenia), low white blood cell counts (neutropenia), and low red blood cell counts (anemia). Patients should tell their doctor right away if they have unexpected bleeding or easy bruising; blood in their urine or stools; fever; or any signs of an infection. SCEMBLIX may increase enzymes in the patient's blood called amylase and lipase, which may be a sign of inflammation of the pancreas (pancreatitis). Patients should tell their doctor right away if they have sudden stomach-area pain or discomfort, nausea, or vomiting. During treatment with SCEMBLIX, doctors may check their patients' blood pressure and treat any high blood pressure as needed. Patients should tell their doctor if they develop elevated blood pressure or symptoms of high blood pressure including confusion, headaches, dizziness, chest pain, or shortness of breath.
If a patient has an allergic reaction while on SCEMBLIX, they should stop taking SCEMBLIX and get medical help right away. Signs or symptoms of an allergic reaction include trouble breathing or swallowing; feeling dizzy or faint; swelling of the face, lips, or tongue; fever; skin rash or flushing; or a fast heartbeat. SCEMBLIX may cause heart and blood vessel problems, including heart attack; stroke; blood clots or blockage of patient's arteries; heart failure; and abnormal heartbeat which can be serious and may sometimes lead to death. These heart and blood vessel problems can happen in people with risk factors or a history of these problems and/or previously treated with multiple TKI medicines. Patients should tell their doctor right away if they get shortness of breath; chest pain or pressure; a feeling like their heart is beating too fast or they feel abnormal heartbeats; swelling in their ankles or feet; dizziness; weight gain; numbness or weakness on one side of their body; decreased vision or loss of vision; trouble talking; pain in their arms, legs, back, neck, or jaw; headache; or severe stomach-area pain.
Before taking SCEMBLIX, patients should tell their doctor about all of their medical conditions, including if they have a history of pancreatitis; a history of heart problems; or blood clots in their arteries and veins (types of blood vessels). SCEMBLIX can harm an unborn baby. Women should tell their doctor right away if they become pregnant or think they may be pregnant during treatment with SCEMBLIX. Women who are able to become pregnant should have a pregnancy test before they start SCEMBLIX and should use effective birth control during treatment and for 1 week after the last dose of SCEMBLIX. Women should not breastfeed during treatment and for 1 week after their last dose of SCEMBLIX.
Patients should tell their doctor about all the medicines they take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements. SCEMBLIX and other medicines may affect each other, causing side effects. The most common side effects of SCEMBLIX include nose, throat, or sinus (upper respiratory tract) infections; muscle, bone, or joint pain; rash; tiredness; nausea; and diarrhea. The most common blood test abnormalities include decreased blood counts of platelets, white blood cells, and red blood cells; and increased blood levels of triglycerides, creatine kinase, liver enzymes, or pancreas enzymes (amylase and lipase).
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*Bosulif is a registered trademark of Pfizer.
Cortes JE, et al. Oral presentation at ASCO 2022; June 3-7, 2022. Chicago, IL and virtual. Abstract 7004.
Rea D, et al. A Phase 3, Open-Label, Randomized Study of Asciminib, a STAMP Inhibitor, vs Bosutinib in CML After≥ 2 Prior TKIs. Blood. 2022. DOI: 10.1182/blood.2020009984. PMID: 34407542.
Scemblix [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.
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ClinicalTrials.gov. 2021. Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT04795427.
Mauro, JM. Efficacy and Safety Results from ASCEMBL, a Multicenter, Open-Label, Phase 3 Study of Asciminib, a First-in-Class STAMP Inhibitor, Vs Bosutinib in Patients with Chronic Myeloid Leukemia in Chronic Phase after ≥2 Prior Tyrosine Kinase Inhibitors: Update after 48 Weeks. Oral presentation at: ASH Annual Meeting; Dec. 11, 2021. Abstract #310.