dm+d

Unassigned

New Medicines

Rivo-cel Primary immunodeficiency and other haematological non-malignant diseases in children and young people undergoing haploidentical haematopoietic stem cell transplant - adjunctive therapy

Information

Rivo-cel
New molecular entity
Bellicum
Bellicum

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase II Clinical Trials
Yes
Yes
Jan 21The company has advised it has paused its effort to pursue a Marketing Authorisation Application from the European Medicines Agency for this indication at this time. NICE is suspending its appraisal [9].
Mar 20Bellicum continues to seek a partner to develop and commercialise rivo-cel. Its active product candidates are BPX-601, BPX-603 and BCMA GoCAR-NK [8].
Dec 19Bellicum is actively pursuing a strategic partner for rivo-cel to lead future development and commercialisation for this product. Bellicum has reduced and expects to continue to reduce its rivo-cel related activities [6].
Dec 16Bellicum anticipates that it could pursue approval in the EU under the “exceptional circumstances” provision [4].
Aug 16European Commission grants orphan drug designation for rivogenlecleucel for treatment in HSCT and for activator agent rimiducid for treatment of GvHD [3].
Feb 16Rivogenlecleucel granted orphan drug status by the US FDA for treatment of immunodeficiency and GvHD after allogeneic HSCT. The FDA designation is for the combination of rivogenlecleucel genetically modified T cells and activator agent rimiducid as replacement T-cell therapy [3].

Category

A genetically modified donor T-cell product. Donor T-lymphocytes are modified with a retroviral vector (BPZ1001) and engineered to express the iCasp9 protein, which acts a “safetyswitch” in the event of graft versus host disease.
Registry data from the British Society of Blood and Marrow Transplantation shows that in 2015–2017 there were between 23 and 40 paediatric haploidentical HSCTs per year. After HSCT treatment it can take six to twelve months blood cell levels and immune cell functions to become near-normal. During this time there is a high rate of transplant rejection, graft versus host disease (GvHD), disease relapse and transplant-related mortality [1].
Primary immunodeficiency and other haematological non-malignant diseases in children and young people undergoing haploidentical haematopoietic stem cell transplant - adjunctive therapy
Intravenous infusion

Further information

Yes
Suspended

Trial or other data

Jul 19Bellicum releases data which show that the primary endpoint of event free survival (EFS) rate at 180 days was met in its PI/II trial assessing rivogenlecleucel in pediatric patients with malignant or non-malignant blood cell disorders undergoing an haplo HSCT (depleted of T cell receptor [TCR] alpha and beta cells) from a partially matched family donor (BP-004; NCT02065869) [7].
Jan 19PI/II trial (NCT02065869), collection of primary outcome data is delayed to Dec 19 [5].
Jan 19PI/II trial (NCT02065869) is no longer recruiting. Collection of primary outcome data is due to complete Jun 19 [2].
Dec 16Bellicum announce interim results from PI/II BP-004 trial. Of 59 pediatric primary immunodeficiencies patients undergoing a haplo-HSCT and treatment with BPX 501, disease-free survival was reported at 88.1% and overall survival was reported at 88.6% with a median follow-up of one year [3].
Apr 14PI/II trial of rivogenlecleucel in 193 paediatric patients aged 3 months to 21 years with haematological malignancies and immunodeficiency disorders undergoing an haplo HSCT from a partially matched donor in the US, UK, Italy and Spain starts (BP-004; NCT02065869). The trial will also evaluate treatment of GvHD by the infusion of dimerizer drug (AP1903/rimiducid) in those subjects who present with GVHD who progress or do not respond to standard of care treatment. The objective is to determine whether rivo-cel could extend relapse-free survival (RFS) and overall survival (OS) via graft versus leukemia (GvL) effect, while maintaining a low-risk of GvHD [2].

Evidence based evaluations

Rivo-cel Haematological malignancies in patients undergoing haploidentical haematopoietic stem cell transplant - adjunctive therapy

Information

Rivo-cel
New molecular entity
Bellicum
Bellicum

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase III Clinical Trials
Yes
Yes
Feb 21The company has advised it has paused its effort to pursue a Marketing Authorisation Application from the European Medicines Agency for this indication at this time. NICE is suspending its appraisal [10].
Mar 20Bellicum continues to seek a partner to develop and commercialise rivo-cel. Its active product candidates are BPX-601, BPX-603 and BCMA GoCAR-NK [8].
Nov 19Bellicum is actively pursuing a strategic partner for rivo-cel that will assume all current and future development and commercialisation responsibilities for this product candidate. If it is unable to identify a partner and reach a license agreement, it will not submit the planned Marketing Authorisation Application (MAA) in order to seek approval to commercialise this product candidate in Europe [6].
Aug 16European Commission grants orphan drug designation for rivogenlecleucel for treatment in HSCT and for activator agent rimiducid for treatment of GvHD [3].
Feb 16Rivogenlecleucel granted orphan drug status by the US FDA for treatment of immunodeficiency and GvHD after allogeneic HSCT. The FDA designation is for the combination of rivogenlecleucel genetically modified T cells and activator agent rimiducid as replacement T-cell therapy [3].

Category

A genetically modified donor T-cell product. Donor T-lymphocytes are modified with a retroviral vector (BPZ1001) and engineered to express the iCasp9 protein, which acts a “safetyswitch” in the event of graft versus host disease.
Registry data from the British Society of Blood and Marrow Transplantation shows that in 2015–2017 there were between 23 and 40 paediatric haploidentical HSCTs per year. After HSCT treatment it can take six to twelve months blood cell levels and immune cell functions to become near-normal. During this time there is a high rate of transplant rejection, graft versus host disease (GvHD), disease relapse and transplant-related mortality [1].
Haematological malignancies in patients undergoing haploidentical haematopoietic stem cell transplant - adjunctive therapy
Intravenous infusion

Further information

Yes
To be confirmed

Trial or other data

Apr 20PII/III THRIVE trial terminated [9].
Jan 20Bellicum suspends patient enrolment in the PII/III THRIVE trial in MDS due to funding and portfolio re-prioritisation (NCT03699475) [7].
Jul 19Bellicum releases data showing Rivo-cel met its primary endpoint of event free survival (EFS) rate at 180 days in its PI/II trial assessing rivogenlecleucel in pediatric patients with malignant or non-malignant blood cell disorders undergoing an haplo HSCT (depleted of T cell receptor [TCR] alpha and beta cells) from a partially matched family donor (BP-004; NCT02065869). The primary endpoints of the PI part were to determine the frequency and severity of adverse events, with the intention of determining a maximum tolerated dose and/or a recommended dose of rivogenlecleucel. The primary endpoints of the PII part were cumulative incidence of non-relapse mortality at 180 and 365 days [5].
Dec 18Bellicum presents results at the 60th Annual Meeting of the American Society of Haematology (ASH-2018) from a PI/II trial of rivogenlecleucel in 193 paediatric patients aged 3 months to 21 years with haematological malignancies and immunodeficiency disorders undergoing an haplo HSCT from a partially matched donor in the US, UK, Italy and Spain (BP-004; NCT02065869). The trial also evaluates the treatment of GvHD by the infusion of dimerizer drug (AP1903/rimiducid) in those subjects who present with GVHD who progress or do not respond to standard of care treatment. The objective was to determine whether rivo-cel could extend relapse-free survival (RFS) and overall survival (OS) via graft versus leukemia (GvL) effect, while maintaining a low-risk of GvHD. In these results, 100 AML and ALL HSCT patients were evaluated for safety. 95 of 100 patients received rivo-cel treatment and therefore were eligible for efficacy evaluation. Patients had a median follow-up of 17 months. Overall survival in 52 ALL patients was 100.0% (CR1) and 89.9% (CR2); in 43 AML patients it was 86.7% (CR1) and 95.7% (CR2). For GvHD outcomes, 21 of 96 evaluable patients developed Grade I-IV acute GvHD (21.9%); 3 patients developed Grade III-IV acute GvHD (3.1% [95% CI: 0 - 6.6%]). 9 cases of late-onset aGVHD occurred after 100 days (2 cases of Grade III). 7 of 89 evaluable patients developed chronic GvHD (10.9% [95% CI: 2.1-19.6%]), with moderate-severe cases in 5 of these patients. Of the 37 patients who developed GvHD, rimiducid was administered to 11 patients. Best overall response (within 7 days) was seen in 73% (8 patients); 5 responding patients had a complete response (CR) and 2 patients with a partial response (PR) went on to achieve a complete response within 30 days following rimiducid administration [3,4].
Dec 18PII/III THRIVE trial to compare the safety and effectiveness of rivogenlecleucel in patients with acute myeloid leukaemia or myelodysplastic syndromes post haploidentical haematopoietic stem cell transplant compared to post-transplant cyclophosphamide starts (BPX501-301A; NCT03699475). In the PII portion, patients will undergo αβ T cell and CD19+ B cell depleted HSCT followed by an infusion of a fixed dose of rivogenlecleucel per kg. These participants will be evaluated for prespecified dose limiting toxicities (DLTs) for a 100-day dose limiting toxicity window. In the PIII portion patients will be enrolled and randomized to one of two treatment arms. Arm A: haplo HSCT plus treatment with rivogenlecleucel and Arm B: haplo HSCT plus post transplant cyclophosphamide. 178 patients aged from 12 years will be recruited in the US. Primary outcome is overall survival; collection of these data is due to complete Dec 23 [2].

Evidence based evaluations