Zdravilo Calquence je v EU odobreno za zdravljenje kronične limfocitne levkemije
Zdravilo Calquence je pokazalo pomembno daljše preživetje brez napredovanja bolezni in ugodno prenašanje tako pri predhodno nezdravljenih kot pri bolnikih s ponovitvijo ali z neodzivno obliko kronične limfocitne levkemije
Zdravilo Calquence (acalabrutinib) družbe AstraZeneca, ki deluje kot selektivni zaviralec Brutonove tirozin kinaze (BTK) naslednje generacije, je bilo odobreno v Evropski uniji (EU) za zdravljenje odraslih bolnikov s kronično limfocitno levkemijo (KLL), najpogostejšo vrsto levkemije pri odrasli.
Odobritev Evropske komisije je temeljila na pozitivnih rezultatih dveh kliničnih raziskav faze III, ELEVATE-TN pri bolnikih s predhodno nezdravljeno KLL in ASCEND pri bolnikih s ponovitvijo ali z neodzivno obliko KLL.1,2 Ta je sledila priporočilu za odobritev Odbora za zdravila za humano uporabo (CHMP) Evropske agencije za zdravila objavljenem julija 2020.
Paolo Ghia, dr. med., direktor strateškega raziskovalnega programa KLL na univerzi Vita-Salute San Raffaele v Milanu, in raziskovalec v klinični raziskavi ASCEND fazi III je dejal: "Ena največjih ovir pri zdravljenju kronične limfocitne levkemije je najti možnost zdravljenja, ki omogoča dolgoročno obvladovanje bolezni in jo bolnik tudi dobro prenaša. KLL namreč običajno prizadene starejše bolnike s sočasnimi boleznimi. Današnje novice zaznamujejo velik napredek pri bolnikih v Evropi, saj so klinične raziskave faze III za zdravilo Calquence pokazale pomembno izboljšanje v primerjavi s sedanjimi standardnimi zdravljenji."
Dave Fredrickson, izvršni podpredsednik enote za onkologijo, je dejal: "Ta odobritev predstavlja ključni napredek za bolnike v Evropi, ki so imeli do sedaj omejene možnosti zdravljenja brez kemoterapije. Zdravilo Calquence, kot naša prva evropska odobritev na področju krvnih rakov, ponuja novo možnost zdravljenja z brezkompromisno učinkovitostjo, ki jo bolniki dobro prenašajo in možnostjo pozitivnega vpliva na kakovost življenja tisočih bolnikov s kronično limfocitno levkemijo."
V klinični raziskavi ELEVATE-TN faze III je zdravilo Calquence v kombinaciji z obinutuzumabom in kot monoterapija pri bolnikih s predhodno nezdravljeno KLL zmanjšalo tveganje za napredovanje bolezni ali smrt za 90% oziroma 80% v primerjavi s standardnim zdravljenjem, kombinacija kemo-imunoterapije klorambucil in obinutuzumab.1 V klinični raziskavi ASCEND faze III je 88 % bolnikov s ponovitvijo ali z neodzivno obliko KLL, ki so jemali zdravilo Calquence, po 12 mesecih ostalo živih in brez napredovanja bolezni v primerjavi z 68 % bolnikov, ki so prejemali rituksimab v kombinaciji z idelalizibom ali bendamustinom.2 Podatki iz vmesnih rezultatov kliničnih raziskav so bili za ELEVATE-TN objavljeni v strokovni reviji The Lancet oziroma za ASCEND v Journal of Clinical Oncology.
Zdravilo Calquence je v ZDA odobreno za zdravljenje KLL in majhnega limfocitnega limfoma (SLL). Za KLL je odobreno v številnih drugih državah po svetu. Zdravilo Calquence je v ZDA in več drugih državah odobreno tudi za zdravljenje odraslih bolnikov z limfomom plaščnih celic (MCL), ki so bili vsaj enkrat predhodno zdravljeni. Zdravilo Calquence trenutno ni odobreno za zdravljenje MCL v Evropi.
Za zdravilo Calquence v sklopu širokega razvojnega programa, ki ga podpira družba AstraZeneca, teče več kot 20 kliničnih raziskav za zdravljenje bolnikov z malignimi boleznimi B-celic, vključno s KLL, MCL, difuznim velikim B-celičnim limfomom (DLBCL), Waldenströmovo makroglobulinemijo (WM), folikularni limfom (FL) in drugimi hematološkimi malignimi boleznimi.
OPOMBE ZA UREDNIKE
Chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in adults, with an estimated 105,000 new cases globally in 2016, and the number of people living with CLL is expected to grow with improved treatment as patients live longer with the disease.3,4,5,6 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections. As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells, and platelets. This could result in anaemia, infection, and bleeding.4 B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.
ELEVATE-TN
ELEVATE-TN (ACE-CL-007) was a randomised, multicentre, open-label Phase III trial evaluating the safety and efficacy of Calquence in combination with obinutuzumab, a CD20 monoclonal antibody, or Calquence alone versus chlorambucil, a chemotherapy, in combination with obinutuzumab in previously untreated patients with CLL. Patients 65 years of age or older, or between 18 and 65 years of age with a total Cumulative Illness Rating Scale >6 or creatinine clearance of 30 to 69mL/min, were enrolled. In the trial, 535 patients were randomised (1:1:1) into three arms. Patients in the first arm received chlorambucil in combination with obinutuzumab. Patients in the second arm received Calquence (100mg approximately every 12 hours until disease progression or unacceptable toxicity) in combination with obinutuzumab. Patients in the third arm received Calquence monotherapy (100mg approximately every 12 hours until disease progression or unacceptable toxicity).1
The primary endpoint was progression-free survival (PFS) in the Calquence and obinutuzumab arm compared to the chlorambucil and obinutuzumab arm, assessed by an independent review committee (IRC), and a key secondary endpoint was IRC-assessed PFS in the Calquence monotherapy arm compared to the chlorambucil and obinutuzumab arm. Other secondary endpoints included objective response rate, time to next treatment and overall survival (OS).1
ASCEND
ASCEND (ACE-CL-309) was a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy of Calquence in patients with relapsed or refractory CLL. In the trial, 310 patients were randomised (1:1) into two arms. Patients in the first arm received Calquence monotherapy (100mg twice daily until disease progression or unacceptable toxicity). Patients in the second arm received investigator's choice of either rituximab, a CD20 monoclonal antibody, in combination with idelalisib, a PI3K inhibitor, or rituximab in combination with bendamustine, a chemotherapy.2
The primary endpoint was PFS assessed by an IRC, and key secondary endpoints included physician-assessed PFS, IRC- and physician-assessed overall response rate and duration of response, as well as OS, patient-reported outcomes and time to next treatment.2
Calquence
Calquence (acalabrutinib) is a next-generation, selective inhibitor of BTK. Calquence binds covalently to BTK, thereby inhibiting its activity.7,8 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.7
As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma are currently evaluating Calquence in more than 20 company-sponsored clinical trials. Calquence is being developed for the treatment of multiple B-cell blood cancers including CLL, MCL, DLBCL, WM, FL, and other haematologic malignancies.
AstraZeneca in haematology
Leveraging its strength in oncology, AstraZeneca has established haematology as one of four key oncology disease areas of focus. The Company's haematology franchise includes two medicines approved by the US Food and Drug Administration and a robust global development programme for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca's haematology research and development arm. AstraZeneca partners with like-minded science-led companies to advance the discovery and development of therapies to address unmet need.
AstraZeneca in oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and haematology.
By harnessing the power of six scientific platforms - Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies - and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
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References
2. Ghia P, et al. ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia [published online ahead of print, 2020 May 27]. J Clin Oncol. 2020; JCO1903355. doi:10.1200/JCO.19.03355.
3. American Cancer Society. What is Chronic Lymphocytic Leukemia? Available at https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/about/what-is-cll.html. Accessed August 2020.
4. National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ®)-Patient Version. Available at https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq. Accessed August 2020.
5. Global Burden of Disease Cancer Collaboration. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016. JAMA Oncol. 2018;4(11):1553-1568.
6. Jain N, et al. Prevalence and Economic Burden of Chronic Lymphocytic Leukemia (CLL) in the Era of Oral Targeted Therapies. Blood. 2015;126:871.
7. Calquence® (acalabrutinib) [prescribing information]. Wilmington, DE; AstraZeneca Pharmaceuticals LP; 2019.
8. Wu J, Zhang M & Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016;9(21).
Adrian Kemp
Company Secretary
AstraZeneca PLC