dm+d

32888011000001103

Refrigerated Storage

DarzalexJanssen-Cilag Ltd

Janssen-Cilag Ltd
Darzalex
1800mg solution for injection

In the event of an inadvertent temperature excursion the following data may be used:
During the shelf-life, the product in unpunctured vials may be stored at room temperature (≤30°C) for a single period of up to 24 hours. Once the product has been taken out of the refrigerator, it must not be returned to the refrigerator.

Contact Janssen-Cilag Ltd in cases where additional stability data is required.

Refer to the current BNF for company contact details.
Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

See above
See above
29 October 2021
London MI Service

Darzalex Janssen-Cilag Ltd

Janssen-Cilag Ltd
Darzalex
20mg/mL concentrate for solution for infusion

Contact Janssen-Cilag Limited in all cases where a deviation from the recommended storage conditions has occurred.

Refer to the current BNF for company contact details.

Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

29 October 2021
London MI Service

New Medicines

DarzalexRelapsed or refractory multiple myeloma (MM) - second- or greater line in combination with carfilzomib and dexamethasone

Information

Darzalex
Licence extension / variation
Janssen-Cilag
Janssen-Cilag

Development and Regulatory status

Launched
Launched
Launched
December 2020
Yes
Yes
Dec 20Licence extension approved in EU and UK [11].
Nov 20Recommended for EU approval by CHMP - the amended indication is use in combination with carfilzomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy [9,10].
Aug 20Approved in the US [8].
Feb 20A supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval of DARZALEX® (daratumumab) in combination with Kyprolis® (carfilzomib) and dexamethasone (DKd) for relapsed/refractory multiple myeloma has been made [7].
Mar 18Has orphan drug status in EU & US [3].
Jul 17PIII in EU & US [1].

Category

Humanised monoclonal antibody that targets CD38, an antigen highly expressed in MM cells & involved in the signalling cascade of antibody-dependent cellular cytotoxicity (ADCC) & complement-dependent cytotoxicity (CDC) pathways
UK incidence of MM is 7.7 per 100,000 people and prevalence is about 16 in 100,000 people. Induction followed by melphalan and ASCT gives the greatest chance of prolonged survival. Almost all patients eventually relapse
Relapsed or refractory multiple myeloma (MM) - second- or greater line in combination with carfilzomib and dexamethasone
Intravenous

Further information

Yes

Trial or other data

Dec 19PIII trial NCT03158688 involving addition of daratumumab to carfilzomib and dexamethasone (DKd), compared to carfilzomib and dexamethasone (Kd) alone, significantly improved progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma, resulting in a 37 percent reduction in the risk of disease progression or death [6].
Jun 19PIII registrational CANDOR study to evaluate daratumumab in combination with carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma starts (NCT03158688). The primary endpoint is progression-free survival (PFS) in 450 patients with multiple myeloma who have received one to three prior therapies. The open-label and two-arm trial intends to enrol approximately 450 patients in the US, Australia and Turkey. Collection of PFS data due to complete Sep 19 [2].
Jan 19Estimated primary completion date of NCT03158688 study brought forward to May 19 [5].
Aug 18NCT03158688 study active but has stopped recruitment. Timescales unchanged [4].

DarzalexSystemic light chain amyloidosis - first-line

Information

Darzalex
Licence extension / variation
Janssen-Cilag
Janssen-Cilag

Development and Regulatory status

Launched
Launched
Launched
June 2021
Jun 21Licence change approved in UK [14].
Jun 21Approved in EU [12].
May 21Recommended for EU approval by CHMP – the new indication is ‘Darzalex is indicated in combination with cyclophosphamide, bortezomib and dexamethasone for the treatment of adult patients with newly diagnosed systemic light chain (AL) amyloidosis’ [11].
Jan 21US FDA grants approval for treatment of light cahin amyloidosis [9].
Nov 20Janssen submits a type II variation application to the European Medicines Agency for the subcutaneous formulation of daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone for use in adult patients with light-chain amyloidosis [10].
Sep 20Filed in US for treatment of light-chain amyloidosis [8].
Jan 20EU & US filings planned for 2020, based on PIII ANDROMEDA study (NCT03201965) [6].
Nov 17Genmab has received a $20 million payout from Janssen Biotech based on progress in the ongoing PIII ANDROMEDA (AMY3001) study of daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone in amyloidosis [3].

Category

Humanised monoclonal antibody that targets CD38, an antigen highly expressed in MM cells & involved in the signalling cascade of antibody-dependent cellular cytotoxicity (ADCC) & complement-dependent cytotoxicity (CDC) pathways
Amyloidosis is a rare disease. However, systemic amyloidosis continues to be fatal and is responsible for about one in 1,500 deaths per year in the UK [1].
Systemic light chain amyloidosis - first-line
Subcutaneous injection

Further information

Yes

Trial or other data

Jun 20Topline results from PIII Andromeda study announced at conference. RCT (n=388) found that SC daratumumab plus CyBorD resulted in a higher haematological complete response rate vs CyBorD (53% vs 18%; OR 5.1; 95% CI[3.2 to 8.2]; P<0.0001) [7].
Sep 19PIII study (NCT03201965) has finished recruiting; collection of primary outcome data is due to complete Feb 20 [5].
Nov 18PIII study (NCT03201965) is still recruiting; timescales unchanged [4].
Sep 17PIII study (NCT03201965) to evaluate the efficacy and safety of daratumumab plus cyclophosphamide, bortezomib and dexamethasone (CyBorD) compared with CyBorD alone in treatment of 370 newly diagnosed AL amyloidosis adults starts in US, Australia, Germany & Sweden. Primary outcome is overall complete haematological response; collection of these data is due to complete Jan 21 [2].

Evidence based evaluations

DarzalexRelapsed or refractory multiple myeloma (MM) - in combination with pomalidomide and dexamethasone for patients who have received at least one prior therapy incl lenalidomide and a proteasome inhibitor

Information

Darzalex
Licence extension / variation
Janssen-Cilag
Janssen-Cilag

Development and Regulatory status

Launched
Launched
Launched
December 2021
Yes
Yes
Dec 21MHRA approves a licence extension for Darzalex to include use in combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received one prior therapy containing a proteasome inhibitor and lenalidomide and were lenalidomide-refractory, or who have received at least two prior therapies that included lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or after the last therapy [12].
Jun 21Approved in EU [11].
May 21Recommended for EU approval by CHMP – the new indication is ‘in combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received one prior therapy containing a proteasome inhibitor and lenalidomide and were lenalidomide-refractory, or who have received at least two prior therapies that included lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or after the last therapy’ [9].
Nov 20Company has also filed APOLLO data with the FDA [8].
Nov 20Filed in EU for use in combination with pomalidomide and dexamethasone (D-Pd) for the treatment of patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy [7].
Jan 20Filings in EU & US planned for 2020 [6].
Jun 17Approved in the US, where daratumumab has Breakthrough Therapy designation, based on data from the Phase I (MMY1001, EQUULEUS) study [1].

Category

Humanised monoclonal antibody that targets CD38, an antigen highly expressed in MM cells & involved in the signalling cascade of antibody-dependent cellular cytotoxicity (ADCC) & complement-dependent cytotoxicity (CDC) pathways
UK incidence of MM is 7.7 per 100,000 people and prevalence is about 16 in 100,000 people. Induction followed by melphalan and ASCT gives the greatest chance of prolonged survival. Almost all patients eventually relapse.
Relapsed or refractory multiple myeloma (MM) - in combination with pomalidomide and dexamethasone for patients who have received at least one prior therapy incl lenalidomide and a proteasome inhibitor
Intravenous

Further information

Yes

Trial or other data

Jun 21PIII APOLLO RCT (n=304) found improved progression free survival with daratumumab plus pomalidomide and dexamethasone vs pomalidomide and dexamethasone alone at median follow up of 16.9 months (12.4 vs 6.9 months, HR 0.63, 95%CI 0.47-0.85) [10].
Jul 19PIII APOLLO study has finished recruiting and is on course to collect primary outcome data by Jun 21 [5].
Apr 18PIII APOLLO study (NCT03180736; MMY3013) is still recruiting. Collection of primary outcome data expected to complete Jun 21 [4].
Jun 17Approval in the US was based on data from the Phase Ib (EudraCT2013-003491-12; 54767414MMY1001; NCT01998971) EQUULEUS study (n=103), which commenced Feb 2014. Patients in the study received 16 mg/kg daratumumab in combination with pomalidomide and dexamethasone. The ORR in the study was 59% (95% CI: 49.1%, 68.8%), with very good partial response (VGPR) achieved in 28% of patients. Complete response (CR) was achieved in 6% of patients and stringent CR (sCR) was achieved in 8% of patients. The median time to response was 1 month (range: 0.9 to 2.8 months). The median duration of response was 13.6 months (range: 0.9+ to 14.6+ months). The most frequent adverse reactions (>20%) in the study were: infusion reactions (50%), diarrhoea (38%), nausea (30%), vomiting (21%), fatigue (50%), pyrexia (25%), upper respiratory tract infection (50%), muscle spasms (26%), cough (43%) and dyspnoea (33%). The overall incidence of serious adverse reactions was 49% [2,3].
May 17European Myeloma Network and Janssen initiated a PIII trial to evaluate daratumumab in combination with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma who have previously been treated with an immunomodulatory drug and a proteasome inhibitor (EudraCT2017-001618-27; APOLLO; MMY3013). The primary endpoint of the study is PFS. Patients will be randomised 1:1 to either receive daratumumab in combination with pomalidomide and dexamethasone, or pomalidomide and dexamethasone alone. The trial is designed to confirm results from the MMY1001 (EQUULEUS) study. The trial will enrol approximately 354 patients. Enrolment is underway in Greece and is expected to extend to other European countries (not UK) [2].

Evidence based evaluations

DarzalexMultiple myeloma (MM) - first-line in transplant ineligible patients in combination with bortezomib, lenalidomide and dexamethasone

Information

Darzalex
Licence extension / variation
Janssen-Cilag
Janssen-Cilag

Development and Regulatory status

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

Category

Humanised monoclonal antibody that targets CD38, an antigen highly expressed in MM cells & involved in the signalling cascade of antibody-dependent cellular cytotoxicity (ADCC) & complement-dependent cytotoxicity (CDC) pathways
The incidence of MM in Europe is 4.5-6.0 per 100,000 per year [1].
Multiple myeloma (MM) - first-line in transplant ineligible patients in combination with bortezomib, lenalidomide and dexamethasone
Intravenous

Further information

Yes

Evidence based evaluations

SMC

DarzalexSmouldering multiple myeloma (MM)

Information

Darzalex
Licence extension / variation
Janssen-Cilag
Janssen-Cilag

Development and Regulatory status

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

Category

Humanised monoclonal antibody that targets CD38, an antigen highly expressed in MM cells & involved in the signalling cascade of antibody-dependent cellular cytotoxicity (ADCC) & complement-dependent cytotoxicity (CDC) pathways
The incidence of MM in Europe is 4.5-6.0 per 100,000 per year. In some patients there is an intermediate asymptomatic but advanced pre-malignant stage. This is called smouldering (or indolent) myeloma. Smouldering myeloma progresses to myeloma at a rate of 10% per year over the first five years following diagnosis, 3% per year over the following five years, and then at a rate of 1.5% per year [1].
Smouldering multiple myeloma (MM)
Intravenous

DarzalexNewly diagnosed multiple myeloma (MM) in adults who are eligible for high-dose chemotherapy with autologous stem cell transplant - in combination with bortezomib, lenalidomide and dexamethasone

Information

Darzalex
Licence extension / variation
Janssen-Cilag
Janssen-Cilag

Development and Regulatory status

None
Phase III Clinical Trials
None

Category

Humanised monoclonal antibody that targets CD38, an antigen highly expressed in MM cells & involved in the signalling cascade of antibody-dependent cellular cytotoxicity (ADCC) & complement-dependent cytotoxicity (CDC) pathways
The incidence of MM in Europe is 4.5-6.0 per 100,000 per year [1].
Newly diagnosed multiple myeloma (MM) in adults who are eligible for high-dose chemotherapy with autologous stem cell transplant - in combination with bortezomib, lenalidomide and dexamethasone
Intravenous