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38994711000001108

New Medicines

CalquenceChronic lymphocytic leukaemia (CLL) - first-line

Information

Calquence
New molecular entity
AstraZeneca
AstraZeneca

Development and Regulatory status

Launched
Launched
Launched
November 2020
Yes
Yes
Nov 20Available in the UK. 100mg yellow/blue cap marked ACA 100mg, 60=£5,059 [22].
Nov 20EU has approved Calquence for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia [21].
Jul 20Recommended for EU approval by CHMP - the full indication is "as monotherapy or in combination with obinutuzumab for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL)"; also "as monotherapy for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy. It is proposed that the medicine be prescribed by physicians experienced in the use of anticancer medicinal products." [20]
Dec 19In the US, Calquence is approved in CLL based on the ASCEND study (monotherapy of patients with relapsed or refractory CLL after at least 1 prior systemic therapy) and the ELEVATE-TN study (combination therapy with obinutuzumab or monotherapy of previously untreated patients with CLL) [17].
Nov 19Filed in EU via centralised procedure [15].
Nov 19Approved in the US [16]
Aug 19Awarded breakthrough therapy designation by FDA [14].
Jan 19Filings in EU and US planned for 2020 [11].
Sep 18Filings planned for H2 19 [10].
Feb 16AstraZeneca announce EU Orphan Drug Status recommended by EMA for CLL (also for small lymphocytic lymphoma, mantle cell lymphoma and lymphoplasmacytic lymphoma (Waldenström’s macroglobulinaemia)) [2]. Company expects to file in US in the second half of 2016 [5].
Jun 15PIII trial in CLL started in US [3].

Category

A second-generation 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) - first-line
Oral

Further information

Yes

Trial or other data

May 20PIII ASCEND (n=398) found that acalabrutinib monotherapy significantly improved progression-free survival (PFS) compared with investigator’s choice of idelalisib plus rituximab or bendamustine plus rituximab (PFS not reached vs 16.5 months, HR 0.31; 95% CI, 0.20 to 0.49, p <0.0001) [13].
Apr 20PIII NCT02475681 is published; in this RCT (n=535), median progression-free survival was longer with acalabrutinib-obinutuzumab (A-O) and acalabrutinib monotherapy (A) than with obinutuzumab-chlorambucil (O-C) (not reached with A-O or A at median follow-up of 28.3 months vs 22.6 months with O-C; both p<0.0001) [19].
Dec 19Topline data from PIII ELEVATE TN trial reported at conference. RCT shows 93% of patients on acalabrutinib with obinutuzumab vs. 47% of patients on chlorambucil plus obinutuzumab remained free of disease progression or death at 24 months [18].
Jun 19PIII ELEVATE-TN trial (n=535) met primary endpoint early at interim analysis resulting in early study completion. Acalabrutinib + obinutuzumab demonstrated a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) vs. the std of care; chlorambucil and obinutuzumab. Acalabrutinib monotherapy also achieved a statistically-significant and clinically-meaningful improvement in PFS compared to the chemotherapy and obinutuzumab regimen (key secondary endpoint). The safety and tolerability of acalabrutinib was consistent with its established profile. Detailed results will be presented at a forthcoming medical meeting. [13]
Jan 19Primary completion date for ELEVATE-TN now estimated to be Dec 19 [12].
Dec 17Data from ELEVATE-TN due 2019 [9].
Sep 15PIII ELEVATE-TN study (ACE-CL-007; NCT02475681) in previously untreated CLL starts. 510 patients will be recruited and will be randomised to acalabrutinib or acalabrutinib plus obinutuzumab or chlorambucil plus obinutuzumab. Primary outcome is PFS and data are anticipated 2019 [7].

Evidence based evaluations

CalquenceRelapsed or refractory chronic lymphocytic leukaemia (CLL)

Information

Calquence
New molecular entity
AstraZeneca
AstraZeneca

Development and Regulatory status

Launched
Launched
Launched
November 2020
Yes
Yes
Nov 20Available in UK. 100mg yellow/blue cap marked ACA 100mg, 60=£5,059 [6].
Nov 20Approved in the EU [15]
Jul 20Recommended for EU approval by CHMP - the full indication is "as monotherapy or in combination with obinutuzumab for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL)"; also "as monotherapy for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy. It is proposed that the medicine be prescribed by physicians experienced in the use of anticancer medicinal products." [20]
Dec 19In the US, Calquence is approved in CLL based on the ASCEND study (monotherapy of patients with relapsed or refractory CLL after at least 1 prior systemic therapy) and the ELEVATE-TN study (combination therapy with obinutuzumab or monotherapy of previously untreated patients with CLL) [11].
Nov 19Filed in EU via centralised procedure [12].
Nov 19Approved in the US [10]
Aug 19Granted breakthrough therapy designation in US [9]
Jan 19Filings in EU and US planned for 2020 [6].
Dec 17Has orphan drug status in EU [2].

Category

A second-generation 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.
Relapsed or refractory chronic lymphocytic leukaemia (CLL)
Oral

Further information

Yes

Trial or other data

Jun 19AstraZeneca announce data from interim analysis of PIII ASCEND study. At 12 months, 88% of patients treated with acalabrutinib show no disease progression vs 68% for rituximab combined with idelalisib or bendamustine [8]
May 19The PIII ASCEND (ACE-CL-309) global multicentre open-label RCT met primary endpoint at interim analysis in 310 pts with relapsed or refractory CLL and will stop early. The trial evaluated efficacy of acalabrutinib monotherapy (100mg twice daily until disease progression) vs. rituximab plus physician’s choice of idelalisib or bendamustine. The primary endpoint of PFS assessed by an independent review committee (IRC) was met with a statistically-significant and clinically-meaningful improvement in PFS with acalabrutinib monotherapy vs. comparator and safety and tolerability were consistent with the known profile.
Dec 18Data now expected from ACE-CL-006 (ELEVATE-RR, NCT02477696) in 2020 or later; data from ACE-CL-309 (NCT02970318) in H2 19 [5].
Dec 17Data expected from ACE-CL-006 (ELEVATE-RR, NCT02477696) in 2019; data from ACE-CL-309 (NCT02970318) in 2020 [1].
Sep 16PIII ACE-CL-309 (NCT02970318) study starts. It will evaluate the efficacy of acalabrutinib compared with rituximab in combination with idelalisib or bendamustine in 306 previously treated subjects with CLL. Primary outcome is progression-free survival and estimated primary completion date is Jan 2020 [1].
Dec 15Outcome of PI/PII studies published online in New England Journal of Medicine, showing a 95% response rate in patients with relapsed CLL [4]
Jun 15PIII trial NCT02477696 started in US. This is a randomized, multi-centre, open-label, non-inferiority trial comparing acalabrutinib to ibrutinib in previously treated subjects with high risk CLL. Primary outcome is progression-free survival and estimated primary completion date is June 2018 [3].

Evidence based evaluations

CalquenceMantle cell lymphoma (MCL) - first-line

Information

Calquence
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes

Category

An orally administered, second generation, potent, selective Brutons (agammaglobulinaemia) tyrosine kinase inhibitor
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) with poor prognosis. MCL accounts for approximately 3% to 6% of new NHL cases in Western countries each year, with an annual incidence of 0.5 per 100,000 persons and an estimated prevalence of 3.5/100,000. The median age at diagnosis is 68 years, with a 3:1 male predominance [1]
Mantle cell lymphoma (MCL) - first-line
Oral

CalquenceRelapsed or refractory chronic lymphocytic leukaemia (CLL) in high-risk patients

Information

Calquence
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Nov 21No plans for filing and removed from pipeline; ELEVATE-RR is not considered a registrational trial [8].

Category

A highly selective and potent BTKi
CLL is the most common leukaemia in the Western world with an incidence of 4.2 per 100,000 per year. The incidence increases to >30 per 100,000 per 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 [1].
Relapsed or refractory chronic lymphocytic leukaemia (CLL) in high-risk patients
Oral

CalquenceChronic lymphocytic leukaemia (CLL) - first line with venetoclax and obinutuzumab

Information

Calquence
Licence extension / variation
AstraZeneca

Development and Regulatory status

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

Category

A second generation, potent, selective Brutons (agammaglobulinaemia) tyrosine kinase inhibitor
CLL is the most common leukaemia in the Western world with an incidence of 4.2 per 100,000 per year [1].
Chronic lymphocytic leukaemia (CLL) - first line with venetoclax and obinutuzumab
Oral