On July 20, 2016 Janssen Inc. reported that Health Canada has approved IMBRUVICA (ibrutinib) an oral, once-daily, single-agent targeted therapy for previously untreated patients with active chronic lymphocytic leukemia (CLL) (Press release, Johnson & Johnson, JUL 20, 2016, View Source [SID:1234513975]). 1 This is the 4th approval for IMBRUVICA , which now is approved for use in all lines of CLL therapy for patients needing treatment, considerably expanding the number of Canadian patients who may benefit from this chemotherapy-free treatment. Chronic lymphocytic leukemia is one of the most common types of leukemia in adults.2 Schedule your 30 min Free 1stOncology Demo! The latest approval is based on data from the Phase 3 RESONATE-2 (PCYC-1115-CA) study, a head-to-head clinical trial comparing IMBRUVICA to chlorambucil (a chemotherapy agent). Results showed using IMBRUVICA first-line was associated with statistically significant improvements in progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) compared with chlorambucil treatment. 3
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"The clinical data showed that IMBRUVICA (ibrutinib) is much more effective than the comparator traditional chemotherapy," says Dr. Carolyn Owen, Associate Professor, Division of Hematology and Hematological Malignancies, Foothills Medical Centre*. "Hopefully, this approval will provide an increase in treatment options for patients with CLL that will ensure their disease is well controlled, allowing them to enjoy their life to the fullest."
The expanded IMBRUVICA indication is based on data from the randomized, international, multi-center, openlabel Phase 3 RESONATE-2 trial, involving 269 previously untreated patients with CLL aged 65 years or older. It showed IMBRUVICA significantly improved PFS, OS and ORR versus chlorambucil. At a median follow up of 18.4 months, the PFS, as assessed by an Independent Review Committee (IRC), indicated an 84 per cent statistically significant reduction in the risk of death or progression in the IMBRUVICA arm versus the chlorambucil arm (HR=0.16 [95 per cent CI, 0.091-0.28]).4 Median PFS was not reached for IMBRUVICA versus 18.9 months for chlorambucil (95 per cent CI: 14.1, 22.0). 5 Analysis of OS demonstrated an 84 per cent statistically significant reduction in risk of death for patients in the IMBRUVICA arm (HR=0.16 [95 per cent CI, 0.048-0.56]). Results also showed a statistically significant improvement in ORR in the IMBRUVICA arm versus the chlorambucil arm (82 per cent versus 35 per cent, respectively; p<0.0001).6 Data from RESONATE-2 were presented in an oral session at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on December 7, 2015, in addition to being featured in the official ASH (Free ASH Whitepaper) press program and simultaneously published online in The New England Journal of Medicine.
"We are pleased with the recent approval of IMBRUVICA by Health Canada," says Shelagh Tippet-Fagyas, president of the Leukemia and Lymphoma Society of Canada. "This approval means broader drug access and options for CLL patients, such as the benefit of earlier chemotherapy-free treatments."
The adverse reactions (AR) reported in the Phase 3 RESONATE-2 trial reflect exposure to IMBRUVICA with a median duration of 17.4 months. 7 The most common ARs (≥20 per cent) of any Grade were diarrhea (42 per cent), musculoskeletal pain** (36 per cent), cough (22 per cent) and rash** (21 per cent). The most common Grade 3/4 AR (>five per cent) was pneumonia** (eight per cent).8 Approximately five per cent of patients receiving IMBRUVICA in the studies supporting the CLL indications (PCYC-1102, RESONATE [PCYC-1112] and RESONATE-2) discontinued treatment due to ARs.9 These reactions included pneumonia, subdural hematoma and atrial fibrillation. ARs leading to dose reduction occurred in approximately four per cent of patients.10 Serious warnings and precautions include major bleeding events (some fatal), not to use in patients with moderate or severe hepatic impairment, and not to use concomitantly with a strong CYP3A inhibitor. Other warnings and precautions include effects on ability to drive and use machines, second primary malignancies, atrial fibrillation and atrial flutter, hypertension, decrease in QTcF interval, drug interactions, tumor lysis syndrome, diarrhea, cytopenias, lymphocytosis, leukostasis, minor bleeding events, infections, perioperative considerations, embryo-fetal toxicity, other reproductive risks, risk of exposure to infants through breast milk, and occurrence of certain adverse events more frequently in the elderly.11
About Chronic Lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia is a slow-growing blood cancer of cells that become white blood cells called lymphocytes, most commonly B cells.12 Chronic lymphocytic leukemia is one of the most common types of leukemia in adults.13 In Canada, there were approximately 2,195 adults diagnosed with CLL in 2010.14 Historically, CLL treatment has been challenging since the more effective treatment regimens were usually associated with high toxicity.15 There has been a real need to develop therapies for CLL that can offer better efficacy and tolerability, especially in older patients. 16
About IMBRUVICA (ibrutinib)
IMBRUVICA contains the medicinal ingredient ibrutinib which is a targeted inhibitor of Bruton’s tyrosine kinase (BTK). Ibrutinib blocks BTK activity, inhibiting cancer cell survival and spread.17 The recommended dose of IMBRUVICA for CLL is 420 mg (three 140-mg capsules) orally, once-daily.18
IMBRUVICA is approved in Canada for the treatment of patients with previously untreated active chronic lymphocytic leukemia (CLL), including those with 17p deletion. It is also approved for the treatment of patients with CLL who have received at least one prior therapy, including those with 17p deletion. IMBRUVICA is approved for the treatment of patients with Waldenström’s macroglobulinemia (WM), and approved (with conditions) for the treatment of patients with relapsed or refractory mantle cell lymphoma (MCL).
IMBRUVICA is co-developed by Cilag GmbH International (a member of the Janssen Pharmaceutical Companies) and Pharmacyclics LLC, an AbbVie company. Janssen Inc. markets IMBRUVICA in Canada.