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33686611000001109

New Medicines

Venclyxto (EU), Venclexta (US)Acute myeloid leukaemia (AML) - first-line in patients unfit for intensive chemotherapy in combination with azacitidine

Information

Venclyxto (EU), Venclexta (US)
Licence extension / variation
AbbVie
AbbVie

Development and Regulatory status

Launched
Launched
Launched
May 2021
Yes
Feb 22MHRA approves a licence change to include use of venetoclax in combination with low dose cytarabine (previously only use in combination with a hypomethylating agent). The new indication is use in combination with a hypomethylating agent or low-dose cytarabine for the treatment of adult patients with newly diagnosed acute myeloid leukaemia who are ineligible for intensive chemotherapy [22].
May 21Approved in EU [21].
May 21Licence change approved in the UK [20].
Apr 21Recommended for EU approval by CHMP - the additional indication is "venetoclax in combination with a hypomethylating agent is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy.” [19].
Oct 20Granted regular approval in the US for use in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC) for newly-diagnosed AML in adults 75 years or older, or who have comorbidities precluding intensive induction chemotherapy [18].
Jun 20EU orphan drug status removed at the request of the company [14].
May 20Filed in EU & US for use in combination with azacitidine for first-line treatment of AML [16].
Apr 20Filings for use of venetoclax with azacitidine are planned for 2020 [12].
Jan 19EU filing will be 2021 or later [9].
Nov 18FDA grants accelerated approval for use in combination with azacitidine, decitabine, or low-dose cytarabine for treatment of adults who are ≥75 years, or have comorbidities that preclude use of intensive induction chemotherapy [8].
Jul 18Filed in US [7].
Feb 18EU & US filings planned for 2018 [6].
Feb 16EMA grants Orphan Drug Designation to venetoclax in AML; it has also been granted Orphan Drug Designation by the FDA [3].
Jan 16FDA award venetoclax breakthrough status designation for use in combination with hypomethylating agents for patients with untreated AML who can´t take standard high-dose chemotherapy [2].

Category

Apoptosis stimulant; proto-oncogene protein c-bcl-2 inhibitor
AML affects < 1.2 in 10,000 people in the EU (equivalent to not more than 61,000 people)
Acute myeloid leukaemia (AML) - first-line in patients unfit for intensive chemotherapy in combination with azacitidine
Oral

Further information

Yes

Trial or other data

Feb 21Viale-C was published in Blood 2020 Jun; 135(24): 2137-45 [18].
Oct 20Viale-A published in NEJM 2020 Aug; 383(7): 617-629 [17].
Aug 20PIII VIALE-A study (n=431) found overall survival was longer (median 14.7 vs. 9.6 months; HR 0.66; 95% CI, 0.52-0.85; p<0.001) and incidence of remission was higher (36.7% vs. 17.9%; p<0.001) among patients who received azacitidine + venetoclax than among those who received azacitidine alone [15].
Jun 20Data from PIII VIALE-A study announced at conference. In study (n=433), patients with AML treated with venetoclax and azacitidine achieved improved median OS (14.7 vs 9.6 months) and a 34% reduction in risk of death (HR 0.66; P=0.001) vs azacitidine alone [13].
Apr 20PIII VIALE-C study (NCT03069352) did not meet its primary endpoint. VIALE-C was studying venetoclax in combination with low-dose cytarabine [12].
Mar 20Positive topline data from the PIII VIALE-A trial (NCT02993523) announced. The study met its primary endpoint and showed venetoclax plus azacitidine helped pts with ALL live longer vs. azacitidine alone and safety for the two medications appeared consistent with the known profiles of these medications. [11]
Mar 20Positive topline data from the PIII VIALE-A trial (NCT02993523) announced. The study met its primary endpoint and showed venetoclax plus azacitidine helped pts with ALL live longer vs. azacitidine alone and safety for the two medications appeared consistent with the known profiles of these medications. [11]
Aug 19PIII trial (NCT02993523) has finished recruiting. Collection of primary outcome data due to complete Feb 20 [10].
May 19PIII trial (NCT03069352) is still recruiting. Collection of primary outcome data due to complete Jul 20 [10].
Dec 17PIII trial (NCT02993523) is still recruiting. PIII trial (NCT03069352) is evaluate efficacy of venetoclax co-administered with low dose cytarabine versus low dose cytarabine in treatment-naïve patients with AML who are ineligible for intensive chemotherapy. Overall survival, measured up to 2 years after the last participant is enrolled, will be the primary endpoint. The randomised, double-blind, placebo-controlled trial is designed to enrol approximately 175 patients globally including US & EU (incl. UK). Collection of primary outcome data due to complete Oct 19 [5].
Jan 17PIII trial (NCT02993523) of venetoclax, in combination with azacitadine, compared with placebo and azacitadine treatment naïve elderly subjects who are ineligible for standard induction therapy has started recruitment. Proportion of patients with complete remission and overall survival are the defined primary endpoint of the trial. Primary completion due February 2020 [4].
Dec 14Abbvie complete PII (NCT01994837) trial investigating the safety and efficacy of venetoclax in relapsed/refractory AML or as front-line therapy for patients who are unfit for intensive treatment [1].
Dec 14Abbvie initiate PII (NCT02287233) study to evaluate safety, efficacy and pharmacokinetics of venetoclax plus low-dose cytarabine regimen, in treatment-naïve patients with AML who are ineligible for anthrocycline-based induction chemotherapy [1].

Evidence based evaluations

Venclyxto (EU), Venclexta (US)Relapsed -positive multiple myeloma - third-line with dexamethasone in patients who have received lenalidomide and a proteasome inhibitor. (11; 14)

Information

Venclyxto (EU), Venclexta (US)
Licence extension / variation
AbbVie
AbbVie

Development and Regulatory status

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

Category

Apoptosis stimulant: selectively blocks the function of the B-cell lymphoma (bcl-2) protein that inhibits apoptosis and is expressed at high levels in many tumours
Age-standardised MM incidence rate for the UK is about 9.5 per 100,000 (2013), with a 13:10 bias to men; it is strongly age-related with peak incidence between 80-89, and it is more common in black people than in white or those of Asian origin [1].
Relapsed -positive multiple myeloma - third-line with dexamethasone in patients who have received lenalidomide and a proteasome inhibitor. (11; 14)
Oral

Further information

Yes

Evidence based evaluations

Venclyxto (EU), Venclexta (US)Relapsed mantle cell lymphoma (MCL) - second-line or greater with ibrutinib

Information

Venclyxto (EU), Venclexta (US)
Licence extension / variation
AbbVie
AbbVie

Development and Regulatory status

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

Category

Novel small molecule that selectively blocks the function of Bcl-2 proteins and with the goal of enhancing apoptosis. Bcl-2 proteins are expressed at high levels in non-Hodgkin lymphoma (NHL), CLL and in other B-cell neoplasms.
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 with ibrutinib
Oral

Further information

Yes

Evidence based evaluations

Venclyxto (EU), Venclexta (US)Myelodysplastic syndromes (MDS) in patients newly diagnosed with higher-risk - in combination with azacitidine

Information

Venclyxto (EU), Venclexta (US)
Licence extension / variation
AbbVie
AbbVie

Development and Regulatory status

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

Category

Novel small molecule that selectively blocks the function of Bcl-2 proteins and with the goal of enhancing apoptosis. Bcl-2 proteins are expressed at high levels in non-Hodgkin lymphoma (NHL), CLL and in other B-cell neoplasms.
Incidence of MDS is approximately 4 per 100,000 population/year. It is predominantly a disease of the elderly with an incidence of over 30 per 100,000/year in those over the age of 70 years. The overall prevalence of the syndromes appears to be increasing due to an ageing population and better diagnosis [1].
Myelodysplastic syndromes (MDS) in patients newly diagnosed with higher-risk - in combination with azacitidine
Oral

Venclyxto (EU), Venclexta (US)Relapsed multiple myeloma (MM) - second-line and beyond with bortezomib and dexamethasone

Information

Venclyxto (EU), Venclexta (US)
Licence extension / variation
AbbVie
AbbVie

Development and Regulatory status

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

Category

Apoptosis stimulant: selectively blocks the function of the B-cell lymphoma (bcl-2) protein that inhibits apoptosis and is expressed at high levels in many tumours
Age-standardised MM incidence rate for the UK is about 9.5 per 100,000 (2013), with a 13:10 bias to men; it is strongly age-related with peak incidence between 80-89, and it is more common in black people than in white or those of Asian origin [1].
Relapsed multiple myeloma (MM) - second-line and beyond with bortezomib and dexamethasone
Oral

Evidence based evaluations