Venetoclax (3) – Venclyxto®

Chronic lymphocytic leukaemia (CLL), monotherapy

Characteristics

Start date 01.12.2018 – Marketing authorisation: 05.12.2016
Resolution 16.05.2019
INN Venetoclax
Brand name Venclyxto®
Pharm. company AbbVie Deutschland GmbH
G-BA Procedure ID D-415
ATC code L01XX52 Other antineoplastic agents (L01XX)
ICD-10 codes (AIS) C91.10Chronic lymphocytic leukemia of B-cell type with failed remission, C91.11Chronic lymphocytic leukemia of B-cell type in remission
Alpha-ID codes (AIS) I25521CLL (chronic lymphocytic leukemia), I31079CLL (chronic lymphocytic leukemia) in complete remission
DDD 0.4 g O
Therapeutic area Oncological diseases Chronic lymphocytic leukemia (CLL)
Reason for procedure Reassessment: Loss of orphan status
Original resolution: Venetoclax (1) (15.06.2017)
Specialty Bundling

Therapeutic indication of the resolution

Venclyxto monotherapy is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL). Venclyxto monotherapy is indicated for the treatment of CLL:

– in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, or

– in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

Subpopulation Indication Comparator
a) Adult patients with chronic lymphocytic leukemia who have a 17p deletion or TP53 mutation and who are ineligible for treatment with a B-cell receptor pathway inhibitor or have shown treatment failure Ibrutinib or idelalisib + rituximab or best supportive care
b) Adult patients with chronic lymphocytic leukemia who do not have a 17p deletion or TP53 mutation and who experienced treatment failure with both chemoimmunotherapy and a B-cell receptor pathway inhibitor Ibrutinib or idelalisib + rituximab or best supportive care

Studies and Results

No. of studies
(best subpopulation)
1 (M14-032)
Study design
(best subpopulation)
Single-arm + historical comparison
Meta analysis
(best subpopulation)
no
Reason for dividing into subpopulations (G-BA) Gene/mutation specifics

  • Clinical trials
    • The pivotal study M13-982 is a single-arm, uncontrolled Phase II study investigating the efficacy and safety of venetoclax in patients with CLL who had a 17p deletion.

a) Adult patients with CLL who have a 17p deletion or TP53 mutation and who are not suitable for treatment with a B-cell receptor signalling pathway inhibitor or who have experienced treatment failure

  • An additional benefit is not proven.
  • To demonstrate additional benefit, the pharmaceutical manufacturer has drawn on the results from relevant patient populations of the pivotal study M13-982 and the supportive study M14-032.
  • However, on the basis of the available, unadjusted historical control, no conclusions can be drawn regarding the additional benefit for adult patients with CLL who have a 17p-deletion or TP53 mutation and who are unsuitable for treatment with a B-cell receptor signalling pathway inhibitor or have failed such therapy.
  • Even taking into account the minor number of patients and, in particular, the magnitude of the treatment effects described in the historical control with the appropriate comparator therapy, it cannot be ruled out with sufficient certainty that potential differences are largely attributable to systematic bias, for example due to relevant differences between the compared populations.
  • Overall assessment
    • Due to their minor statistical power, the evidence presented is not suitable for assessing the additional benefit of venetoclax. Overall, the additional benefit for patient population a) is not proven.

b) Adult patients with CLL who do not have a 17p deletion or TP53 mutation and who have experienced treatment failure both with chemoimmunotherapy and with a B-cell receptor signalling pathway inhibitor

  • The additional benefit is not proven.
  • To demonstrate additional benefit in this patient population b, the pharmaceutical manufacturer has also drawn on the results for relevant patients from the M14-032 study.
  • Due to their minor statistical power, the evidence provided is, on the whole, not suitable for assessing the additional benefit of venetoclax.
  • Overall, the additional benefit for adult patients with CLL without a 17p deletion or TP53 mutation, who have experienced treatment failure both with chemo-immunotherapy and with an inhibitor of the B-cell receptor signalling pathway, No proof has been provided.
  • Overall assessment
    • Overall, the evidence provided is not sufficient to assess the additional benefit of venetoclax due to its minor statistical power. Consequently, an additional benefit for patient group b) is not proven.

Courtesy translation only, please refer to the German original.

Associated procedures

Venetoclax (7) Venclyxto® AbbVie Deutschland GmbH & Co. KG Oncological diseases Chronic lymphocytic leukaemia, first-line treatment, combination of acalabrutinib with or without obinutuzumab n.d. active procedure
Venetoclax (6) Venclyxto® AbbVie Deutschland GmbH & Co. KG Oncological diseases Chronic lymphocytic leukaemia, first-line treatment, combination with ibrutinib n.d. active procedure
Venetoclax (5) Venclyxto® AbbVie Deutschland GmbH & Co. KG Oncological diseases Acute myeloid leukaemia (AML), combination therapy, first-line 560–840 100% Hint for considerable additional benefit
Venetoclax (4) Venclyxto® AbbVie Deutschland GmbH & Co. KG Oncological diseases Chronic lymphocytic leukaemia (CLL), first-line, in combination with obinutuzumab 3,090–3,099 100% additional benefit not proven
Venetoclax (2) Venclyxto® AbbVie Deutschland GmbH Oncological diseases Chronic lymphocytic leukaemia (CLL), combination with rituximab 2,000–7,200 37% Indication of minor additional benefit
Venetoclax (3) Venclyxto® AbbVie Deutschland GmbH Oncological diseases Chronic lymphocytic leukaemia (CLL), monotherapy 300–700 100% additional benefit not proven
Venetoclax (1) Venclyxto® AbbVie Deutschland GmbH Oncological diseases Chronic lymphocytic leukaemia (CLL), monotherapy 0
300–700
100% non-quantifiable additional benefit Orphan repealed


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