The world's first BCMA targeted therapy! GlaxoSmithKlynte (Belantamab mafodotin) has been approved for listing by the FDA!

!--Webeditor:page title"--August 06, 2020 // -- GlaxoSmithKill (GSK) recently announced that the U.S. Food and Drug Administration (FDA) has approved Blenrep (belantamab mafodotin, GSK2857916), a drug Antibody drug concatenation (ADC), which targets B-cell mature antigens (BCMA), is used as a single-drug therapy to treat adult patients with recurrent or recurrent multiple myeloma (MM) who have previously received at least 4 therapies, including an anti-CD38 antibody, a protease inhibitor, and an immunomodant.
, based on tumor remission rate data, the ordnance was approved through an accelerated approval process.
approval for the orthosis will depend on the validation and description of clinical benefits in validation trials.
, Blenrep is the world's first BCMA targeted therapy and GSK's fifth major drug approval in 2020.
Blenrep uses a multi-role mechanism to target BCMA, a cell surface protein that plays an important role in plasma cell survival and is expressed in multiple myeloma cells.
is currently under EU review and is expected to be approved within two months.
, the drug was awarded Breakthrough Drug Qualification (BTD) and Priority Drug Qualification (PRIME) in the United States and the European Union, respectively, and was the first BCMA targeting agent to be awarded BTD and PRIME.
notably, the FDA's Internal Reviewer expressed concern about Blinkrep's eye-related adverse events, but the FDA's Advisory Committee on Oncology Drugs (ODAC) voted 12-0 to approve Blinkrep.
As the second most common blood cancer in the United States, multiple myeloma is an incurable and devastating disease," said Dr. Hal Barron, Chief Scientific Officer and President of Research and Development at GlaxoSmithKill.
Blenrep is the world's first approved anti-BCMA therapy that has the potential to transform the current selection of clinical treatments for patients with limited recurrent or incurable myeloma.
" approval is based on data from the DREAMM clinical trial project, including critical DREAMM-2 studies.
This is a randomized, open-label, two-arm Phase II study that included 196 patients with previously overtreated R/R MM patients who, despite current standard treatments, worsened their condition, had a median of seven treatment options received in the past, had difficulty treating immunomodating drugs and protease inhibitors, and were resistant to CD38 antibody difficulties and/or intolerance.
, patients were randomly divided into two groups and treated with a dose of Blenrep every three weeks (Q3W) at 2.5 mg/kg or 3.4 mg/kg dose.
The six-month preliminary results of the study, published in The Lancet Oncology in December 2019, are also the basis for the US-European regulatory application document: the overall remission rate of Blenrep 2.5mg/kg Q3W single-drug treatment (ORR) was 31% (97.5%CI: 21-43), and the duration of mid-level remission (DoR) had not yet been reached, but in patients with remission (responders), 73% had DoR for 6 months.
most common adverse reactions (-20%) are corneal lesions, vision loss, nausea, blurred vision, fever, infusion-related reactions and fatigue.
corneal lesions are characterized by changes in the corneal epidural, which, as seen during eye examinations, can manifest as asymptomatic.
of the 218 patients in the aggregate safety group, 77 per cent had adverse eye reactions, including corneal lesions (76 per cent), vision changes (55 per cent), blurred vision (27 per cent) and dry eyes (19 per cent).
adverse corneal events are monitored through an eye examination before each dose, allowing for dose reduction or interruption when appropriate.
patients also used eye potions without preservatives.
in the 2.5mg/kg group, the corneal lesions that led to the suspension affected 2.1% of patients.
at the end of May this year, GSK published 13-month follow-up data for the study at the 2020 Annual Meeting of the American Society of Clinical Oncology (ASCO), which showed that the ORR for single-drug therapy at Blenrep (2.5mg/kg, Q3W) was 31% (Consistent with 6-month data), medium mitigation duration (DoR) was 11 months (95%CI:4.2-not reached), and total midsebrance survival (OS) was 14.9 months (95%CI:9.9-not reached).
in patients in remission, the majority (58%) had achieved very good partial or better remission (?VGPR), including 2 cases of strict total remission (sCR) and 5 cases of complete remission (CR).
36% (95%CI:26.6-46.5) of patients who received clinical benefits.
long follow-up, no new safety signals were found.
Of the patients receiving 2.5 mg/kg doses, the most common adverse events of level 3 or higher (which occurred in more than 10% of patients) were corneal lesions/microcystic algae-like epidural changes (MEC; 46%), plateboard reduction (22%), anemia (21%), decreased lymphocytic count (13%) and a decrease in neutral granulocytes (11%).
the first case of corneal lesions (MEC) is characterized by changes in corneal epidural cells seen during eye examinations and the appearance or non-symptomasis.
, 77 per cent of patients in the 2.5 mg/kg dose group were treated at the end of the data, and no permanent vision loss has been reported to date.
for R/R MM patients who receive currently available treatments but the disease is still progressing, treatment options are very limited and the prognosis is poor.
results of the DREAM-2 study are further evidence of the potential of Blenrep.
approval of the drug will provide these patients with an important new treatment option to help address significant unstreated medical needs. the
belantamab mafodotin mechanism OFAMM clinical development project, which includes 10 clinical studies (DREAMM-1 to DREAMM-10), is evaluating the efficacy and safety of Brenrep as a single-drug therapy and for combination therapy for first-, second- and multi-line therapy MM.
data from DREAM-1, the first human clinical study, released earlier this year, showed that the total remission rate (ORR) of Blenrep treatment reached 60% in BCMA-positive R/R MM patients.
!--/ewebeditor:page-!--ewebeditor:page title"--GSK also published data from the DREAMM-6 study at ASCO's annual meeting.
The study was conducted in R/R MM patients who had relapsed after receiving one or more treatments to investigate the efficacy and safety of Blenrep (2.5mg/kg, Q3W) combined boratezomi/BorDex.
preliminary results showed that the total remission rate (ORR) of Blenrep combined BorDex (B-Vd) treatment reached 78% (n-14/18; 95%CI: 52.4-93.6), 50% was very good partial remission (VGPR) and 28% was partial remission (PR).
83% (95%CI:58.6-96.4) of patients who received clinical benefits (minimal remission or better).
18.2 weeks of treatment, the mid-level DoR had not yet been achieved.
of stage 3 or above include corneal lesions (MEC; 56%) and plate plateboard reduction (61%).
no level 4 MEC cases.
These preliminary results confirm the potential of Blenrep combination therapy in early patients with multiple myeloma BCMA as a target in the study of MM immunotherapy (source literature - PMID: 31277554) multiple myeloma (MM) is the second most common hematologic malignancies after non-Hodgkin's lymphoma.
in recent years, despite significant progress in chemotherapy, protease inhibitors, immunomodants saridomin derivatives, and CD38 targeted antibodies, almost all patients will eventually relapse.
therefore, there is an urgent need for new treatment options.
MM market is close to $14 billion in 2017 and is expected to reach nearly $29 billion in 2027.
BCMA is an extremely important B-cell biomarker, widely found on the surface of MM cells, and has become a very popular immunotherapy target for MM and other blood system malignant tumors in recent years.
Currently, there are more than 20 immunotherapy treatments developed for BCMA, divided into three main categories: chimedic antigen receptor T-cell therapy (CAR-T, 100MSK/Bluebird Bio, Novarro), bisexitive antibodies (BsAb, Amgen as representative), and antibody drug contums (ADC, represented by GlaxoSmithKline).
Blenrep is a new type of humanized Fc-modified anti-BCMA monoantigenic and cytotoxic preparation MMAF (monomethyl auristatin-F) that is contly linked by a non-lysis linker (drug-linking technology is licensed from Seattle Genetics).
Brenrep binds to BCMA on the surface of MM cells by anti-BCMA monoantigens, which are then rapidly internalized by MM cells, degraded in lysogens and release non-permeable MMAF into MM cells.
MMAF is a filamented division inhibitor, an anti-microphageal protein compound that inhibits cell division by blocking microcell polymerization, stopping tumor cells in the G/M phase and inducing the apoptosis of caspase-3 dependence.
addition, Blenrep induces NK cell-mediated ADCC (antibody-dependent cell-mediated cytotoxicity) while inducing macrophage-mediated ADCP (antibody-dependent cell-mediated phagocytosic).
Blenrep selectively acts on MM cells through a variety of cytotoxic mechanisms, providing a promising next-generation immunotherapy option for this type of cancer.
, Blenrep is also being developed for use in other patients with advanced blood system malignancies that express BCMA.
() Original source: FDA approves GSK's BLENREP (belantamab mafodotin-blmf) for the treatment of the patients with relapsed or refractory multiple myeloma !--/ewebeditor:page-.