GSK's anti-BCMA drug for multiple myeloma has been approved and is back in the anti-tumor field.

On August 6, 2020, GlaxoSmithKline (GSK) announced that its multiple myeloma drug belantamab mafodotin had been approved by the FDA.
2017, the drug was approved by the FDA for breakthrough therapies designed to facilitate research into the development of drugs.
while the safety and efficacy of the drug remains open to debate, the FDA believes the benefits outweigh the risks for patients in general.
the drug's commercial name is BLENREP, which sells for $23,900 a month.
S. see for details: Targeting BCMA's ADC drug belantamab mafodotin, obtaining FDA Advisory Group support for the treatment of patients with recurrent or incurable multiple myeloma, and the first antibody drug targeted at BCMA, Blenrep, was approved by the FDA for accelerated FDA approval: Treatment of recurrent or reframeable multiple myeloma, based on data from the DRAMM clinical trial project, including critical DREAM-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.
see: Key research on the anti-BCMA drug belantamab mafodotin for multiple myeloma reaches its main end point, but eye toxicity is also of concern: antibody-drug concatenation Belanamab mafodotin: Alarming eye toxicity At the end of May this year, GSK published the study's 13-month follow-up data at the 2020 Annual Meeting of the American Society of Clinical Oncology (ASCO). ORR for single-drug treatments of rep (2.5mg/kg, Q3W) was 31% (consistent with 6-month data), median remission duration (DoR) was 11 months (95%CI:4.2-not achieved), and median total survival (OS) was 14.9 months (95% CI:9.9-not achieved).
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.
, Chief Scientific Officer and President of Research and Development at GSK, said, "Multiple myeloma is the second most common blood cancer in the United States and an incurable and devastating disease.
BLENREP is the first approved anti-BCMA treatment with the potential to change current treatments for patients with recurrent or recurrent myeloma.
" Belantamab mafodotin mechanism OFAMM clinical development project includes 10 clinical studies (DREAMM-1 to DREAMM-10) and is evaluating the efficacy and safety of Brenrep as a single-drug therapy and for combination therapy for first-, second- and multi-line therapies.
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.
at ASCO's annual meeting, GSK also released data from the DREAM-6 study.
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.
Blenrep is an antibody concatenation drug that is made up of humanized anti-B cell mature antigen (BCMA) monoclonal antibodies and the cytotoxic drug auristatin F (auristatin F) through non-cut connections.
2017, Blenrep was recognized by the FDA as a breakthrough therapy.
the end of 2019, GSK submitted a biologics license application (BLA) for the drug to the FDA, which subsequently granted it priority review status.
July 14 this year, GSK announced that the FDA Advisory Committee on Oncology Medicine (ODAC) had voted 12-0 in support of candidate drugs that would benefit more than risk in treating patients with recurrent/incurable multiple myeloma.
It is worth noting that the product was approved by clinical trials in China in May this year for the use of combined boratezomi and desemethone for the treatment of adult patients with multiple myeloma who have received at least one previous treatment.
both for the field of multiple myeloma and for GSK itself, the approval of BLENREP has a significant role to play.
is the first FDA-approved anti-BCMA drug in the field of multiple myeloma.
BCMA is a protein that has been expressed in multiple myeloma cells, and researchers have been trying to target it for more than a decade.
addition to BLENREP, a range of other BCMA drugs are currently performing well in early trials and are likely to be available in the next few years.
for GSK, it is the first cancer drug the British giant has developed in-house since its deal with Novartis in 2014.
GSK transferred almost all of its cancer treatment drug deals to Novartis in 2014 in exchange for a portfolio of vaccines and infectious disease drugs.
GSK, led by Hal Barron, sees the approval as a signal to the outside world that GSK is beginning to return to the anti-tumor field.
although the impact of BLENREP may be limited from a medical or market perspective.
because the drug may be weakened by the toxicity of antibody-drug concathings, other late-stage anti-BCMA drugs have shown more favorable results in recent trials.
GSK said patients in key trials lived longer than those of other patients at that stage, but the FDA said in its internal review that the company's end-of-life was "unsealable" because there was no control group.
However, BLENREP had an overall remission rate (ORR) of 31% (97.5% CI; 21-43) in patients whose drugs, including Darzalex, Johnson and Johnson's best-selling drug, were ineffective, and the FDA considered the treatment "probably beneficial."
, however, is that the drug's benefits outweigh the risks. According to clinical trials, the drug can cause a side effect called corneal lesions, blurring vision in some patients and even leading to "severe vision loss" in some patients.
Of the 218 patients who participated in the safety test, 77 percent had adverse eye reactions, including corneal lesions (76 percent), vision changes (55 percent), blurred vision (27 percent) and dry eyes (19 percent).
that before each dose, the doctor monitors the cornea through an eye examination in order to reduce or interrupt the dose as appropriate.
patients also used eye potions without preservatives.
2.5 mg / kg in the queue, as corneal lesions caused 2.1% of patients to stop treatment.
industry analysts generally agree that this risk is not unacceptable for patients who are already on the last line of treatment, and that the FDA advisory board has voted 12-0 to approve its listing.
, however, they also believe that patients in the early stages of the disease are less likely to accept these risks, and that other treatments currently in clinical development may be more attractive than them.
other treatments for BCMA protein include CAR-T therapy developed jointly by Johnson and Johnson and Lenovo Biotechnology, and "ide-cel" CAR-T therapy developed by Bluebird and Bristol Myers Squibb (BMS).
, the remission rate was 100% and 89%, respectively, in patients in the early stages.
addition, both regenerative meta and Amgen have BCMA dual-specific drugs in the study, in which regenerative meta drugs in early trials have shown better results.
for now, GSK will have its own side in the fight against cancer when the drug is launched, but in the long run, the market advantage they rely on could be enormous.