dm+d

28393111000001103

New Medicines

ImbruvicaChronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma - first-line in young fit patients in combination with rituxumab

Information

Imbruvica
Licence extension / variation
Janssen-Cilag
Pharmacyclics & Janssen

Development and Regulatory status

Launched
Launched
Launched
August 2020
Yes
Yes
Aug 20Approved in EU [10].
Jul 20First-line use of ibrutinib in combination with rituximab for CLL is for recommended for EU approval by CHMP - the amended CLL indication is as a single agent or in combination with rituximab or obinutuzumab ... for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) [9].
Apr 20FDA approve ibrutinib in combination with rituximab for CLL or SLL in pts new to therapy.[8]
Jan 20Filed in EU [7].
Nov 19AbbVie has submitted a supplemental New Drug Application to the U.S. FDA for ibrutinib in combination with rituximab for the first-line treatment of younger patients (70 years old or younger) with chronic lymphocytic leukemia or small lymphocytic lymphoma [6].
Dec 17Will be filed in EU via centralised procedure [1].
Dec 17Has orphan drug status in EU & US [3].

Category

A selective Bruton's tyrosine kinase (Btk) inhibitor
CLL is the most common leukaemia in the Western world with an incidence of 4.2 per 100,000 a year. The incidence increases to more than 30 per 100,000 a year at an age of >80 years. The median age at diagnosis is 72 years. About 10% of CLL patients are reported to be younger than 55 years.
Chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma - first-line in young fit patients in combination with rituxumab
Oral

Further information

Yes
Suspended

Trial or other data

Aug 19Results of PIII NCT02048813 (n=529) are published; the authors report at median follow-up of 33.6 months, ibrutinib–rituximab resulted in superior progression-free survival vs. standard chemoimmunotherapy (89.4 vs. 72.9% at 3 years; HR 0.35; 95% CI, 0.22 to 0.56; p<0.001) among patients age ≤70 years with previously untreated CLL [5].
Dec 18Latest results from the PIII National Cancer Institute-sponsored PIII Study (E1912; NCT02048813) presented at the annual American Society of Hematology meeting. At a median follow-up of 33.4 months, ibrutinib plus rituximab showed significantly prolonged PFS vs FCR in previously untreated patients aged 70 years or younger with CLL/SLL (HR: 0.35; 95% CI: 0.22-0.56; p<0.0001). The study also demonstrated an improved OS for the ibrutinib plus rituximab treatment arm vs FCR (HR: 0.17; 95% CI: 0.05-0.54; p=0.0003). In a subgroup analysis for PFS, ibrutinib plus rituximab showed prolonged PFS independent of age, sex, performance status (0-2), disease stage, or the presence/absence of deletion 11q23 [4].
Feb 14PIII study in approximately 519 patients starts in the US (NCT02048813). It will assess ibrutinib and rituximab to see how well they work compared to fludarabine phosphate, cyclophosphamide, and rituximab in treating patients with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. Collection of primary outcome data (PFS and quality of life) is due to complete Mar 20 [2].

Evidence based evaluations

ImbruvicaMantle cell lymphoma (MCL), newly diagnosed in adults aged >64 years

Information

Imbruvica
Licence extension / variation
Janssen-Cilag
Pharmacyclics & Janssen

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

First-in-class selective Bruton's tyrosine kinase (Btk) inhibitor
MCL is a rare and aggressive type of non-Hodgkin’s lymphoma (NHL), comprising 5-10% of newly diagnosed cases of NHL. Approximately 600-1,200 new cases are diagnosed each year in the UK.
Mantle cell lymphoma (MCL), newly diagnosed in adults aged >64 years
Oral

Further information

Yes
To be confirmed

Evidence based evaluations

ImbruvicaRelapsed or refractory marginal zone lymphoma

Information

Imbruvica
Licence extension / variation
Janssen-Cilag
Pharmacyclics & Janssen

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Launched
Yes
Jan 17Approved in US for treatment of patients requiring systematic therapy who have received at least one prior anti-CD20 therapy [6].
Sep 16Filed in US for treatment of patients with MZL who require systemic therapy. The filing is based on data from the PCYC-1121 trial (NCT01980628) [5].
Aug 15Orphan designation (EU/3/15/1541) granted by the European Commission to Janssen-Cilag for ibrutinib for treatment of marginal zone lymphoma [4].

Category

First-in-class selective Bruton's tyrosine kinase (Btk)
Non-Hodgkin lymphoma is the sixth most common cancer in the UK; in 2011, approximately 12,800 new cases of non-Hodgkin’s lymphoma were diagnosed accounting for 4% of all new cases in the UK. It is estimated that MZL together with follicular lymphoma account for one-fifth of all non-Hodgkin cases [1].
Relapsed or refractory marginal zone lymphoma
Oral

Further information

Yes
To be confirmed

Trial or other data

Nov 18PII (NCT01980628) study final analysis results posted (n=63). Mean ORR 46% (33.5 to 59.3). Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months. Median duration of response (DOR) was not reached - NA (16.7 to NA) [7].
Oct 17PII (NCT01980628) study completes [7].
Dec 13PII (NCT01980628) study begins. This open-label, non-randomised, monotherapy study will evaluate safety and efficacy of ibrutinib in 60 pts with relapsed/refractory Marginal Zone Lymphoma (MZL) recruited from sites in the US, Belgium, France, Germany & UK. Collection of primary outcome data (overall response rate) should complete Dec 17 [3].
Nov 13PII (NCT01980628) study is ongoing but no longer recruiting pts. Collection of primary outcome data should compete in Feb 2016 [3].

Evidence based evaluations

ImbruvicaRelapsed or refractory follicular lymphoma (FL)

Information

Imbruvica
Licence extension / variation
Janssen-Cilag
Pharmacyclics & Janssen

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

First-in-class selective Bruton's tyrosine kinase (Btk)
The two most common types of NHL are DLBCL and follicular lymphomas. Annual incidence of DLBCL is 5-6/100,000 (increasing from 0.3/100,000 in those aged 35-39 years to 26.6/100,000 in those aged 80-84 years). Annual incidence of follicular lymphomas has increased from 2-3/100,000 during the 1950s to 5-7/100,000 recently [2].
Relapsed or refractory follicular lymphoma (FL)
Oral

Further information

Yes
To be confirmed

ImbruvicaChronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma - first-line in Binet Stage A patients with risk of early disease progression

Information

Imbruvica
Licence extension / variation
Janssen-Cilag
Pharmacyclics & Janssen

Development and Regulatory status

None
Phase III Clinical Trials
None
Yes
Yes
Nov 19AbbVie has submitted a supplemental New Drug Application to the U.S. FDA for ibrutinib in combination with rituximab for the first-line treatment of younger patients (70 years old or younger) with chronic lymphocytic leukemia or small lymphocytic lymphoma [6].
Dec 17Has orphan drug status in EU & US [3].
Dec 17Will be filed in EU via centralised procedure [1].

Category

A selective Bruton's tyrosine kinase (Btk) inhibitor
CLL is the most common leukaemia in the Western world with an incidence of 4.2 per 100,000 a year. The incidence increases to more than 30 per 100,000 a year at an age of >80 years. The median age at diagnosis is 72 years. About 10% of CLL patients are reported to be younger than 55 years.
Chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma - first-line in Binet Stage A patients with risk of early disease progression
Oral

Trial or other data

Aug 19Results of PIII NCT02048813 (n=529) are published; the authors report at median follow-up of 33.6 months, ibrutinib–rituximab resulted in superior progression-free survival vs. standard chemoimmunotherapy (89.4 vs. 72.9% at 3 years; HR 0.35; 95% CI, 0.22 to 0.56; p<0.001) among patients age ≤70 years with previously untreated CLL [5].
Dec 18Latest results from the PIII National Cancer Institute-sponsored PIII Study (E1912; NCT02048813) presented at the annual American Society of Hematology meeting. At a median follow-up of 33.4 months, ibrutinib plus rituximab showed significantly prolonged PFS vs FCR in previously untreated patients aged 70 years or younger with CLL/SLL (HR: 0.35; 95% CI: 0.22-0.56; p<0.0001). The study also demonstrated an improved OS for the ibrutinib plus rituximab treatment arm vs FCR (HR: 0.17; 95% CI: 0.05-0.54; p=0.0003). In a subgroup analysis for PFS, ibrutinib plus rituximab showed prolonged PFS independent of age, sex, performance status (0-2), disease stage, or the presence/absence of deletion 11q23 [4].
Feb 14PIII study in approximately 519 patients starts in the US (NCT02048813). It will assess ibrutinib and rituximab to see how well they work compared to fludarabine phosphate, cyclophosphamide, and rituximab in treating patients with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. Collection of primary outcome data (PFS and quality of life) is due to complete Mar 20 [2].

ImbruvicaRelapsed mantle cell lymphoma (MCL) - second-line or greater in combination with venetoclax

Information

Imbruvica
Licence extension / variation
Janssen-Cilag
Pharmacyclics & Janssen

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes

Category

First-in-class selective Brutons tyrosine kinase (Btk) inhibitor
The two most common types of NHL are DLBCL and follicular lymphomas. Overall annual incidence of DLBCL in Europe is 3.8/100,000. Annual incidence of follicular lymphomas has increased from 2-3/100,000 during the 1950s to 5-7/100,000 recently. Mantle cell lymphoma accounts for about 3-10% of all cases of NHL. Mantle cell lymphoma is more common in the over-50s and is three times more common in men than in women [1].
Relapsed mantle cell lymphoma (MCL) - second-line or greater in combination with venetoclax
Oral

ImbruvicaGraft versus host disease (GvHD) - first-line

Information

Imbruvica
Licence extension / variation
Janssen-Cilag
Pharmacyclics & Janssen

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Oct 20No longer listed in latest global pipeline; presume all development discontinued [7].
Sep 20Janssen has decided to put on hold the filing for regulatory approval in Europe for this indication [6].

Category

A selective Bruton's tyrosine kinase (Btk) inhibitor
Immunosuppressed patients who receive white blood cells from another person are at risk of GVHD. The incidence of acute GVHD varies widely ranging from 10-80%, depending on risk factors [3].
Graft versus host disease (GvHD) - first-line
Oral

Further information

Yes
To be confirmed

Evidence based evaluations