dm+d

39215511000001100

Refrigerated Storage

BlenrepGSK

GSK
Blenrep
100mg powder for concentrate for solution for infusion

In the event of an inadvertent temperature excursion the following data may be used:

The vials are stable for a cumulative time of up to 120 hours at temperatures between 8°C and 30°C and up to 24 hours at temperatures between 25°C and 40°C.

The vials are stable for a cumulative time of up to 120 hours at temperatures between 2°C and -20°C for one event.

The product can be returned to the fridge and no change in expiry dates is required if exposed to the above conditions.

20 December 2021
London MI Service

New Medicines

BlenrepRelapsed or refractory multiple myeloma (MM) - fifth-line monotherapy

Information

Blenrep
New molecular entity
GlaxoSmithKline
GlaxoSmithKline

Development and Regulatory status

Launched
Licensed but not launched
Licensed but not launched
July 2021
Yes
Yes
Jul 21Blenrep 100mg powder for conc for soln for inf in vial available in the UK. Price for 1 vial = £5707.83 [14].
Aug 20Approved in EU [13]
Aug 20Approved by the FDA via the accelerated approvals pathway; indication is "for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent" [12]. As for EMA conditional approval, further clinical data may be required for continued approval.
Jul 20Recommended for EU conditional approval by CHMP - the full indication is "as monotherapy for the treatment of multiple myeloma in adult patients, who have received at least four prior therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.” The medicine should be prescribed by physicians experienced in the treatment of multiple myeloma. [11] Conditional approval indicates that the information available is less than would usually be required, but that the medicine fulfils a significant unmet need and the benefit to risk balance is considered to be acceptable under those circumstances; the manufacturer will normally be expected to provide further clinical data to retain the marketing authorisation.
Jul 20The US FDA’s Oncologic Drugs Advisory Committee (ODAC) unanimously voted, 12 to 0, to recommend belantamab mafodotin as a monotherapy for relapsed or refractory multiple myeloma in pts who have had >4 previous therapies.[10]
Jul 20In a briefing document, the FDA expressed safety concerns regarding keratopathy which affected 71% of pts in a PII study. In the PII study, of 97 pts who received the lower dose, 44% had at least one instance of severe keratopathy including many asymtpomatic cases, which makes detection difficult. No patients have lost their vision permanently. The company is working on plans to mitigate risks but the FDA briefing notes that despite implementing dose modifications, ocular toxicities were recurrent and persistent and that these side effects could limit its use.[9]
Feb 20Filed in the EU with accelerated assessment status [8].
Dec 19Biologics License Application (BLA) submitted to US FDA for the 2.5 mg/kg dosage.[6]
Mar 19Has orphan drug status in EU & US [4].
Nov 17FDA grants Breakthrough Therapy designation to GSK-2857916 monotherapy in patients with multiple myeloma who have failed at least three prior lines of therapy, including an anti-CD38 antibody and are refractory to a proteasome inhibitor and an immunomodulatory agent [4].
Oct 17EMA grants PRIME designation to GSK 2857916 for treatment of relapsed and refractory multiple myeloma patients whose prior therapy included a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody [4].

Category

Humanised IgG1 monoclonal antibody-drug conjugate (ADC) consisting of an antibody that targets the B-cell maturation antigen (BCMA), linked to monomethyl auristatin F (mcMMAF), an anti-tubulin agent.
The incidence in Europe of MM 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) - fifth-line monotherapy
Intravenous infusion

Trial or other data

Dec 19Positive data from PIII DREAMM-2 trial (n=97) published in The Lancet Oncology. Pts who had actively progressing and refractory MM were randomised to receive belantamab mafodotin 2.5 mg/kg or 3.4 mg/kg every 3 weeks. Belantamab mafodotin showed a clinically meaningful overall response rate (ORR) of 31% with 2.5 mg/kg and of that subgroup, 18 acheived very good partial response or better, with 3 pts acheiving complete responses. Overall survival data are not yet available.[6,7]
Aug 19GSK announces results from pivotal DREAMM-2 PII open-label, randomised study of two doses of belantamab mafodotin for multiple myeloma. The 196 trial pts had relapsed multiple myeloma, were refractory to an immunomodulator, proteasome inhibitor, and an anti-CD38 antibody. The two-arm study met its primary objective and demonstrated clinically meaningful overall response rate. Safety and tolerability were consistent with DREAMM-1 [5].
Sep 18PI/II DREAMM-6 trial to evaluate safety, tolerability, and clinical activity of GSK-2857916 administered in combination with lenalidomide plus dexamethasone (arm A), or bortezomib plus dexamethasone (arm B) in participants with relapsed or refractory MM starts (NCT03544281). The open-label trial is enrolling approximately 90 patients in the US. Collection of primary outcome data (complete response and safety data) is due to complete Jun 20 [2,3].
Jun 18PII DREAMM-2 trial to evaluate safety and efficacy of GSK-2857916 in patients with MM who had three or more prior lines of treatment, are refractory to a proteasome inhibitor and an immunomodulatory agent and have failed an anti-CD38 antibody treatment starts (NCT03525678). 155 patients will be recruited in the US, Australia, Canada, France, Germany, Italy, Spain & UK. Primary outcome is overall response rate; collection of these data is due to complete Jun 19 [3].

Evidence based evaluations

BlenrepRelapsed or refractory multiple myeloma (MM) - third-line monotherapy

Information

Blenrep
Licence extension / variation
GlaxoSmithKline
GlaxoSmithKline

Development and Regulatory status

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

Category

Humanised IgG1 monoclonal antibody-drug conjugate (ADC) consisting of an antibody that targets the B-cell maturation antigen (BCMA), linked to monomethyl auristatin F (mcMMAF), an anti-tubulin agent. Given via a 1-hour infusion every 3 weeks.
The incidence in Europe of MM 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) - third-line monotherapy
Intravenous infusion

BlenrepRelapsed or refractory multiple myeloma (MM) - second-line combination therapy with pomalidomide and dexamethasone

Information

Blenrep
Licence extension / variation
GlaxoSmithKline
GlaxoSmithKline

Development and Regulatory status

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

Category

Humanised IgG1 monoclonal antibody-drug conjugate (ADC) consisting of an antibody that targets the B-cell maturation antigen (BCMA), linked to monomethyl auristatin F (mcMMAF), an anti-tubulin agent.
The incidence in Europe of MM 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) - second-line combination therapy with pomalidomide and dexamethasone
Intravenous infusion

BlenrepRelapsed or refractory multiple myeloma (MM) - second-line combination therapy with bortezomib and dexamethasone

Information

Blenrep
Licence extension / variation
GlaxoSmithKline
GlaxoSmithKline

Development and Regulatory status

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

Category

Humanised IgG1 monoclonal antibody-drug conjugate (ADC) consisting of an antibody that targets the B-cell maturation antigen (BCMA), linked to monomethyl auristatin F (mcMMAF), an anti-tubulin agent.
The incidence in Europe of MM 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) - second-line combination therapy with bortezomib and dexamethasone
Intravenous infusion

Blenrep Relapsed or refractory multiple myeloma (MM) - fourth-line monotherapy

Information

Blenrep
Licence extension / variation
GlaxoSmithKline
GlaxoSmithKline

Development and Regulatory status

Not approved
Not approved
Not approved
Yes
Yes
Sep 20The EMA did not approve Blenrep for fourth-line use as only 5 patients in the pivotal study had 3 previous treatments, and the majority of the patients were heavily pre-treated, with two proteasome inhibitors and two immunomodulatory agents. In addition, most of the patients were refractory to bortezomib, carfilzomib, lenalidomide and pomalidomide and, by definition, all patients in the pivotal study were refractory to an immunomodulatory agent and a proteasome inhibitor and an anti-CD38 antibody [12].
Aug 20The FDA approved Blenrep only for fifth-line use, not fourth-line [13].
Jul 20Not recommended for approval for use after three previous therapies. Instead the CHMP recommended conditional approval for use as monotherapy for the treatment of multiple myeloma in adult patients, who have received at least four prior therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy [11].
Jul 20The US FDA Oncologic Drugs Advisory Committee (ODAC) unanimously voted, 12 to 0, to recommend belantamab mafodotin as a monotherapy for relapsed or refractory multiple myeloma in patients who have had >4 previous therapies but not after three therapies. GSK is confident that Blenrep can be developed for all earlier lines [9,10].
Feb 20Filed in the EU with accelerated assessment status [8].
Nov 19Biologics License Application (BLA) submitted to US FDA for the 2.5 mg/kg dosage [7].
Mar 19Has orphan drug status in EU & US [6].
Nov 17FDA grants Breakthrough Therapy designation to GSK-2857916 monotherapy in patients with multiple myeloma who have failed at least three prior lines of therapy, including an anti-CD38 antibody and are refractory to a proteasome inhibitor and an immunomodulatory agent [6].
Oct 17EMA grants PRIME designation to GSK 2857916 for treatment of relapsed and refractory multiple myeloma patients whose prior therapy included a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody [6].

Category

Humanised IgG1 monoclonal antibody-drug conjugate (ADC) consisting of an antibody that targets the B-cell maturation antigen (BCMA), linked to monomethyl auristatin F (mcMMAF), an anti-tubulin agent.
The incidence in Europe of MM 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) - fourth-line monotherapy
Intravenous infusion

Further information

Yes

Trial or other data

Dec 19Positive data from PII DREAMM-2 trial (n=97) published in The Lancet Oncology. Pts who had actively progressing and refractory MM were randomised to receive belantamab mafodotin 2.5 mg/kg or 3.4 mg/kg every 3 weeks. Belantamab mafodotin showed a clinically meaningful overall response rate (ORR) of 31% with 2.5 mg/kg and of that subgroup, 18 acheived very good partial response or better, with 3 pts acheiving complete responses. Overall survival data are not yet available [4.5].
Aug 19GSK announces results from pivotal DREAMM-2 PII open-label, randomised study of two doses of belantamab mafodotin for multiple myeloma. The 196 trial pts had relapsed multiple myeloma, were refractory to an immunomodulator, proteasome inhibitor, and an anti-CD38 antibody. The two-arm study met its primary objective and demonstrated clinically meaningful overall response rate. Safety and tolerability were consistent with DREAMM-1 [3].
Jun 18PII DREAMM-2 trial to evaluate safety and efficacy of GSK-2857916 in patients with MM who had three or more prior lines of treatment, are refractory to a proteasome inhibitor and an immunomodulatory agent and have failed an anti-CD38 antibody treatment starts (NCT03525678). 155 patients will be recruited in the US, Australia, Canada, France, Germany, Italy, Spain & UK. Primary outcome is overall response rate; collection of these data is due to complete Jun 19 [2].

Evidence based evaluations