Jazz Pharmaceuticals Announces the Poster Publication of Vyxeos® Liposomal (daunorubicin and cytarabine) Long-Term Phase 3 Data for Newly Diagnosed High-Risk/Secondary Acute Myeloid Leukaemia at EHA Annual Congress

Five-year data demonstrate improved overall survival was maintained for older adults treated with Vyxeos liposomal versus 7+3 chemotherapy 

[OXFORD, UK], June 12, 2020 – Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced positive results from a prospectively planned, final five-year analysis of a pivotal Phase 3 study comparing outcomes for Vyxeos^® liposomal (daunorubicin and cytarabine), also known as CPX-351, versus 7+3 chemotherapy in older adults with newly diagnosed, high-risk/secondary acute myeloid leukaemia (AML).* Data from the analysis were published as a poster at the virtual European Hematology Association (EHA) Annual Congress.[1] The data were also shared as a poster during the virtual American Society of Clinical Oncology (ASCO) Annual Meeting in May.[2]

“Blood cancers like high-risk/secondary AML progress rapidly and are life-threatening,” said Sam Pearce, senior vice president, Europe & Rest of World at Jazz Pharmaceuticals. “The overall survival advantage for Vyxeos liposomal observed in the five-year data analysis offers real hope to patients and their families in the treatment of this devastating cancer.”

The Phase 3 study was an open-label, randomised trial of 309 patients aged 60 to 75 years with newly diagnosed high-risk/secondary AML who received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary endpoint was overall survival (OS). The Kaplan-Meier–estimated survival rate was higher for CPX-351 versus 7+3 at three years (21% vs 9%) and at five years (18% vs 8%). The reported adverse reactions with CPX-351 were generally consistent with the known safety profile of cytarabine and daunorubicin therapy in the Phase 3 study.¹

The five-year follow-up observational data demonstrate that improved median OS with CPX-351 was maintained in the overall study population as well as among patients who achieved complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CRi) and those who underwent haematopoietic cell transplant (HCT). After a median follow-up of 60.65 months (10th-90th percentile: 58.22-63.90), improved median OS was maintained with a hazard ratio that was very stable and consistent with the prior primary endpoint analysis (HR=0.70 [95% CI: 0.55-0.91]). In patients who achieved CR or CRi (CPX-351: n=73 [48%]; 7+3: n=52 [33%]), median OS was improved with CPX-351 versus 7+3 (21.72 versus 10.41 months).¹

More than one-third of patients (53/153; 35%) went on to receive HCT after receiving CPX-351, compared to one-quarter of those treated with 7+3 (39/156; 25%). Among those who underwent HCT, the Kaplan-Meier–estimated survival rate landmarked from the date of HCT was higher for CPX-351 versus 7+3 at five years (52% versus not estimable). Additionally, median OS landmarked from the date of HCT was not reached for CPX-351 versus 10.25 months for 7+3 (HR=0.51 [95% CI: 0.28–0.90]). Among patients who achieved CR or CRi, 41/73 (56%) in the CPX-351 arm and 24/52 (46%) in the 7+3 arm subsequently underwent HCT. In these patients, median OS landmarked from the date of HCT was not reached for CPX-351 versus 11.65 months for 7+3.¹

About Vyxeos Liposomal

In the US, Vyxeos^® (daunorubicin and cytarabine) is a liposomal formulation of a fixed combination of daunorubicin and cytarabine for intravenous infusion that represents a chemotherapy treatment option specifically for two types of high-risk/secondary acute myeloid leukaemia (AML): newly diagnosed therapy-related AML (t-AML) and AML with myelodysplasia-related changes (AML-MRC).[3] In Europe, Vyxeos liposomal (daunorubicin/cytarabine) is indicated for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukaemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).[4] Backed by a clinical development programme including Phase 3 data, Vyxeos liposomal is currently approved in more than 30 countries, and Jazz continues to work with regulatory authorities worldwide to bring this therapy to appropriate patients.

View the Summary of Product Characteristics here: http://pp.jazzpharma.com/pi/vyxeos.en.SPC.pdf

About CombiPlex

The CombiPlex technology evaluates drug combinations to identify the most effective, synergistic ratios that optimise anti-tumour activity.[5] It then pairs this combination with an extremely small scale (nanoparticle-size) delivery system that can be targeted directly at tumour tissues or cells.⁵ CombiPlex utilises two proprietary nano-scale delivery platforms: liposomes to control the release and distribution of water-soluble drugs and drugs that are both water- and fat-soluble (amphipathic), and nanoparticles to control the release and distribution of non-water-soluble (hydrophobic) drugs.[6]

About AML

AML is a rare type of blood cancer that begins in the bone marrow and is characterised by the uncontrolled growth and division of abnormal myeloid cells.[7]^,[8],[9] AML cells often move quickly from the bone marrow into the blood stream, where they can spread to other parts of the body.[10] The median age at diagnosis is 72 and AML prognosis progressively worsens with age.[11]^,[12] There is also reduced tolerance for intensive chemotherapy as patients age.[13] People with therapy-related AML (t-AML) and AML with myelodysplasia-related changes (AML-MRC), two different types of secondary AML, have some of the poorest survival rates of all AML types.^11,12 A haematopoietic cell transplant (HCT) may be a treatment option for some patients.[14]

In the European Union, there are an estimated 18,400 new cases of AML each year.[15]

About Jazz Pharmaceuticals plc

Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharmaceutical company dedicated to developing life-changing medicines for people with serious diseases — often with limited or no options. We have a diverse portfolio of marketed medicines and novel product candidates, from early- to late-stage development, in key therapeutic areas. Our focus is in neuroscience, including sleep medicine and movement disorders, and in oncology, including haematologic and solid tumours. We actively explore new options for patients including novel compounds, small molecule advancements, biologics and innovative delivery technologies. Jazz is headquartered in Dublin, Ireland and has employees around the globe, serving patients in more than 90 countries.

Reporting Adverse Events

Adverse events should be reported. Healthcare professionals are asked to report any suspected adverse events via their national reporting system. In the United Kingdom, reporting forms and information can be found at https://yellowcard.mhra.gov.uk/. Adverse events should also be reported to Jazz Pharmaceuticals by email: AEreporting@jazzpharma.com or by fax to: +44 (0) 1865 598765.

[1] Lancet J, et al. Five-Year Final Results of a Phase 3 Study of CPX-351 Versus 7+3 in Older Adults with Newly Diagnosed High-Risk/Secondary Acute Myeloid Leukemia. Poster presented at: European Hematology Association (EHA); June 11-21, 2020. Abstract Code: EP556.

[2] Lancet JE, Uy GL, Newell LF, et al. Five-year final results of a Phase 3 study of CPX-351 versus 7+3 in older adults with newly diagnosed high-risk/secondary AML. Poster presented at: American Society of Clinical Oncology ASCO20 Virtual Scientific Program; May 29-31, 2020. Poster Number: 283.

[3] FDA. Orphan Drug Designation and Approval: Vyxeos Liposomal. Available at https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=265808 Last accessed May 2020.

[4] European Medicines Agency. Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/vyxeos-liposomal-epar-product-information_en.pdf. Last accessed May 2020.

[5] Tolcher AW, Mayer LD. Improving combination cancer chemotherapy: the CombiPlex® development platform. Future Oncol. 2018; 14(13), 1317-1332.

[6] Ma et al. Nanoparticles for Combination Drug Therapy. ACS Nano. 2013; 7(11):9518-25

[7] Grove CS and Vassilou GS. Acute Myeloid Leukaemia: A Paradigm for the Clonal Evolution of Cancer? Disease Models & Mechanisms. 2014; 7:941-951.

[8] American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML). Available at: https://www.cancer.org/cancer/acute-myeloid-leukemia/about/key-statistics.html Last accessed May 2020.

[9] NHS Conditions. Acute Myeloid Leukaemia. Available at: https://www.nhs.uk/conditions/acute-myeloid-leukaemia/ Last accessed May 2020.

[10] American Cancer Society. About Acute Myeloid Leukemia (AML). Available at: https://www.cancer.org/cancer/acute-myeloid-leukemia/about/what-is-aml.html Last accessed May 2020.

[11] Roman E et al. Myeloid malignancies in the real-world: Occurrence, progression and survival in the UK’s population-based Haematological Malignancy Research Network. 2004-2015. Cancer Epidemiology 2016; 42: 186-198.

[12] HMRN Incidence. AML. Available at: https://www.hmrn.org/statistics/incidence Last accessed May 2020.

[13] Klepin HD. Geriatric perspective: how to assess fitness for chemotherapy in acute myeloid leukemia. ASH Education Program Book. 2014, 5;2014(1):8-13.

[14] European Medicines Agency. Orphan Maintenance Assessment Report. Available at: https://www.ema.europa.eu/en/documents/orphan-maintenance-report/vyxeos-orphan-maintenance-assessment-report-initial-authorisation_en.pdf Last accessed May 2020.

[15] European Medicines Agency. Assessment Report: Vyxeos. EMA/486480/2018. 28 June 2018. Available at: https://www.ema.europa.eu/en/documents/assessment-report/vyxeos-epar-public-assessment-report_en.pdf  Last accessed June 2020.