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New Medicines

Abecma Relapsed or refractory multiple myeloma in adults who have received a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody

Information

Abecma
New molecular entity
Celgene
bluebird bio & Celgene

Development and Regulatory status

Phase II Clinical Trials
Approved (Licensed)
Launched
Yes
Yes
Aug 21Approved in EU [21].
Jun 21Recommended for conditional EU approval by CHMP – the full indication is “Abecma for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least three previous therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and whose cancer has worsened since receiving the last treatment. As Abecma is a gene therapy, the CHMP’s positive opinion is based on an assessment by EMA’s Committee for Advanced Therapies. Abecma will be available as a 260-500 x 10⁶ CAR-positive viable T cells dispersion for infusion [20].
Apr 21Launched in the US with list price of $419,500 per dose [18]
Mar 21Approved in US for treatment of adults with relapsed/refractory multiple myeloma [18].
Mar 21Company requests an extension to the clock stop to respond to the list of outstanding issues adopted in February 2021 by the EMA CHMP. The clock resumes when the company has sent its responses. This will delay an EU approval decision [19].
Sep 20FDA grants priority review to idecabtage with a PDUFA date of March 27th, 2021. [15]
Sep 20FDA grants priority review to idecabtage with a PDUFA date of March 27th, 2021. [15]
Jul 20BMS and Bluebird Bio announce resubmission of NDA to US FDA. Submission includes further detail on the Chemistry, Manufacturing and Controls (CMC) module to address outstanding regulatory requests [14].
Jun 20Has orphan drug status in EU & fast track status in US [13].
May 20EMA validates Bristol Myers Squibb’s application for idecabtagene vicleucel for treatment of adults with MM who have received at least 3 prior therapies, including a proteasome inhibitor and an anti-CD38 antibody. It was granted Accelerated Assessment status in March.[12]
May 20FDA issue a ´Refusal to File´ letter as additional data is requried. BMS intend to resubmit the application by end of July [11].
Mar 20Filed in the US for treatment of adults with MM who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. The submission of BLA is based on the results from the PII KarMMa trial [9].
Aug 19bluebird bio announces intention to file in EU for Multiple myeloma (Second-line therapy or greater) in 2019 [6].
Mar 19bluebird bio has patent protection related to lentiviral vectors utilised to develop idecabtagene vicleucel [6].
Nov 17Granted PRIME status in EU. Filing will be via centralised procedure [1].
Nov 16EMA CAT considers autologous anti-BCMA CAR-T cells fall within the definition of a gene therapy medicinal product, i.e. an ATMP [4].

Category

Autologous chimeric antigen receptor (CAR)-T cell therapy. T-lymphocytes are collected from the patient by leukapheresis and modified genetically ex vivo with a lentiviral vector that targets BCMA. Re-infused as a single dose.
MM is the second most common haematological cancer, responsible for 15-20% of deaths from haematological cancer and about 2% of all deaths from cancer. Incidence in Europe is 4.5-6.0 per 100,000 per year with a mortality rate of 4.1 per 100,000 per year [3].
Relapsed or refractory multiple myeloma in adults who have received a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody
Intravenous infusion

Further information

Yes
To be confirmed

Trial or other data

Feb 21Results of PII KarMMa trial published in NEJM [17].
Feb 21Feb 21: Results of PII KarMMa trial published in NEJM [17].
May 20Results from the PII KarMMa trial, presented at ASCO 2020, show an overall response rate (ORR) of 73% across all dose levels that included a complete response rate (CR) or stringent CR observed in 33% of patients. Progression free survival was reported to be 8.6 months. MRD-negative was reported among patients who were evaluable for minimal residual disease (MRD) and had CR and sCR. Across doses, the CR rate was 31%, median time to response was 1 month (range, 0.5-8.8), and median DOR was 10.6 months (95% CI, 9.0-11.3). Subgroups including older and high-risk patients had an ORR of 50%. Furthermore, the data illustrated ORR of 50% (2), 68.6% (48), 81.5% (44) and 73.4% (94) at doses 150 x 106, 300 x 106, 450 x 106 and 150 x 106 respectively. At dose 150 x 106 , CR/sCR was found to be 25% (1) while it was 28.6% (20), 35.2% (19) and 31.3% (40) at doses 300 x 106, 450 x 106 and 150 x 106 respectively. The median duration of response observed at 300 x 106, 450 x 106 and 150 x 106 was 9.9 months, 11.3 months and 10.6 months respectively. The median PFS seen was 5.8 months, 11.3 months and 8.6 months at doses 300 x 106, 450 x 106 and 150 x 106 respectively [16].
Apr 20Idecabtagene has been prioritised for potential TA guidance production. Topic has been passed to scoping team to prepare for a consultation exercise [10].
Dec 19No UK trial sites [8]
Dec 19Further positive data from pts whose MM was refractory to a median of 6 prior treatments. Of pts on the lowest dose (150 million cells/kg), tumors shrank in 10 out of 12 pts (83%) and eliminated them in 4 pts. Of the 14 pts on the middle dose (300 million cells/kg) and of the 7 pts taking the highest dose (450 million cells/kg), 10 saw tumors shrink. None of the pts who saw tumors shrink have had their disease worsen after a median follow-up of 4 months to date. The lowest dose kept cancer from growing or spreading for a median of 11 months, with one patient still responding >20 months. Of the 38 pts treated, 66% developed cytokine release syndrome (CRS) of which 1 pt died and 1 required aggressive treatment. The most common side effect was neutropenia.[7]
May 19Interim PI study (NCT02658929) data for bb2121 in treatment of multiple myeloma have demonstrated that 15 patients from the first 33 to be treated with bb2121 have experienced a full response, and a further nine patients have had a partial response. Six of the 15 patients experiencing a complete response then went on to relapse [5].
Feb 18PII KarMMA study (NCT03361748) has completed recruitment. Estimated study completion date November 2023 [3,4].
Dec 17PII KarMMa study (NCT03361748) to evaluate the efficacy and safety of bb2121 in subjects with relapsed and refractory MM is recruiting patients. A leukapheresis procedure will be performed to manufacture bb2121 chimeric antigen receptor (CAR) modified T cells. Prior to bb2121 infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide. 94 patients will be recruited in the US. Primary outcome is overall response rate (ORR); collection of these data are due to complete Nov 23 [2].

Evidence based evaluations

Abecma Relapsed or refractory multiple myeloma (MM) in adults who have received at least 2 but no greater than 4 prior MM regimens

Information

Abecma
Licence extension / variation
Celgene
bluebird bio & Celgene

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes
Sep 19Has orphan drug status in EU & fast track status in US [4].
Sep 19Has orphan drug status in US [3].

Category

Autologous chimeric antigen receptor (CAR)-T cell therapy. T-lymphocytes are collected from the patient by leukapheresis and modified genetically ex vivo with a lentiviral vector that targets BCMA. Re-infused as a single dose.
MM is the second most common haematological cancer, responsible for 15-20% of deaths from haematological cancer and about 2% of all deaths from cancer. Incidence in Europe is 4.5-6.0 per 100,000 per year with a mortality rate of 4.1 per 100,000 per year [1].
Relapsed or refractory multiple myeloma (MM) in adults who have received at least 2 but no greater than 4 prior MM regimens
Intravenous infusion

Trial or other data

Aug 20PIII KarMMa-3 study continues to recruit. Collection of primary outcome data is now due to finish May 22 [6].
Dec 19No UK trial sites [5]
Aug 19PIII KarMMa-3 study is recruiting [2].
Oct 18PIII KarMMa-3 study to evaluate the safety and efficacy of idecabtagene vicleucel, versus standard triplet starts (NCT03651128; EudraCT2018-001023-38). 381 adults will be recruited in the US, Canada, Belgium and Spain. Subjects must have received at least 2 but no greater than 4 prior MM regimens, and must have received prior treatment with DARA, a proteasome inhibitor- and an immunomodulatory compound-containing regimen for at least 2 consecutive cycles. Collection of primary outcome data (progression-free survival) is due to complete Jun 25 [2].

Abecma Relapsed or refractory multiple myeloma (MM) in adults - second-line

Information

Abecma
Licence extension / variation
Celgene
bluebird bio & Celgene

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase II Clinical Trials
Yes
Yes
Dec 20Has orphan drug status in US [5].
Jun 20Has orphan drug status in EU [3].

Category

Autologous chimeric antigen receptor (CAR)-T cell therapy. T-lymphocytes are collected from the patient by leukapheresis and modified genetically ex vivo with a lentiviral vector that targets BCMA. Re-infused as a single dose.
MM is the second most common haematological cancer, responsible for 15-20% of deaths from haematological cancer and about 2% of all deaths from cancer. Incidence in Europe is 4.5-6.0 per 100,000 per year with a mortality rate of 4.1 per 100,000 per year [1].
Relapsed or refractory multiple myeloma (MM) in adults - second-line
Intravenous infusion

Trial or other data

Oct 20PII KarMMa-2 study is recruiting. Collection of primary outcome data now expected to complete Oct 21 [4].
Jan 20PII KarMMa-2 study is recruiting [2].
Nov 18PII KarMMa-2 study to evaluate the efficacy and safety of idecabtagene vicleucel, in patients with relapsed-refractory and high-risk multiple myeloma, having progressed within one year of initial treatment starts (BB2121-MM-002; NCT03601078). The primary endpoints of the trial will be overall response rate (ORR) and complete response (CR). This study is a multi-cohort, open-label study to evaluate bb2121 in subjects with relapsed and refractory MM (Cohort 1), in subjects with MM having progressed within one 18 months of initial treatment including autologous stem cell transplantation (ASCT) (Cohort 2a), and without ASCT (Cohort 2b) or, in subjects with inadequate response post ASCT during initial treatment (Cohort 2c) Approximately 181 subjects will be enrolled into one of two cohorts. Cohort 1 will enroll approximately 73 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens. Cohort 2a will enroll approximately 39 MM subjects, with 1 prior anti-myeloma therapy including ASCT and with early relapse. Cohort 2b will enroll approximately 39 MM subjects with 1 prior anti-myeloma therapy not including ASCT and with early relapse. Cohort 2c will enrol approximately 30 MM subjects with inadequate response to ASCT during their initial anti-myeloma therapy. The cohorts will start in parallel and independently. Patients will be recruited in the US, France, Germany, Spain and the UK (sites include Kings College Hospital). Collection of primary outcome data is due to complete Mar 25 [2].