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European Commission Approves Blenrep (Belantamab Mafodotin) For The Treatment Of Patients With Relapsed And Refractory Multiple Myeloma

Published: Aug 26, 2020 2:06 pm
  • BLENREP is the first anti-BCMA (B-cell maturation an­ti­gen) ther­apy ap­prov­ed in the Euro­pean Union
  • Marketing autho­ri­sa­tion follows the recent US ap­prov­al of BLEN­REP

European Commission Approves Blenrep (Belantamab Mafodotin) For The Treatment Of Patients With Relapsed And Refractory Multiple Myeloma London, United Kingdom (Press Release) – GlaxoSmithKline plc to­day an­nounced the Euro­pean Com­mis­sion has granted con­di­tional mar­ket­ing autho­ri­sa­tion for BLEN­REP (belantamab mafo­dotin) 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. BLEN­REP is a first-in-class humanised anti-BCMA (B-cell maturation an­ti­gen) treat­ment for these patients whose dis­ease has progressed de­spite the cur­rent stan­dard of care.

Dr Hal Barron, Chief Scientific Of­fi­cer and Pres­i­dent R&D, GSK, said: “The ap­prov­al of BLEN­REP marks an im­por­tant step for­ward for patients in Europe where nearly 50,000 new cases of mul­ti­ple myeloma are diag­nosed each year. Unfortunately, most of these patients will relapse or stop re­spond­ing to cur­rent ther­a­pies so I am pleased that to­day’s news will give patients with lim­ited treat­ment op­tions access to the first ap­prov­ed anti-BCMA ther­apy.”

The ap­prov­al is based on data from the pivotal DREAMM-2 (DRiving Excellence in Approaches to Multiple Myeloma) study, in­clud­ing 13-month follow-up data. These data dem­onstrated that treat­ment with single-agent BLEN­REP, admin­istered as a 2.5 mg/kg dose every three weeks (Q3W), re­­sulted in an over­all re­sponse rate of 32%. The median duration of re­sponse was 11 months and median over­all sur­vival was 13.7 months.

The safety and tol­er­a­bil­ity profile were con­sis­tent with pre­vi­ously re­ported data on BLEN­REP. The most commonly re­ported ad­verse events in the 2.5 mg/kg arm (greater than or equal to 20%) were ker­a­top­a­thy/microcyst-like epithelial changes or MECs (71%), thrombo­cyto­penia (38%), anaemia (27%), blurred vision events (25%), nausea (25%), pyrexia (23%), in­creased aspartate amino­trans­ferase (AST) (21%), in­fusion-related re­ac­tions (21%), and lymphopenia (20%).

Dr Katja Weisel, Deputy Director and Asso­ci­ate Pro­fessor of Hae­ma­tol­ogy/Oncology in the De­part­ment of Oncology, Hae­ma­tol­ogy and Bone Marrow Transplantation with De­part­ment of Pneumo­nol­ogy, Uni­ver­sity Medical Centre Hamburg-Eppendorf in Germany and an in­ves­ti­ga­tor for the DREAMM-2 trial, said: “Despite ad­vances in treat­ment, mul­ti­ple myeloma re­mains incurable and patients con­tinue to cycle through ther­a­pies, with their prog­nosis worsening with each relapse. The ap­prov­al of BLEN­REP, with its novel mech­a­nism of action, rep­re­sents a new class of treat­ment that patients can turn to when their can­cer stops re­spond­ing to other stan­dard of care op­tions.”

BLENREP employs a multi-faceted mech­a­nism of action and is directed to­ward BCMA, a cell-surface pro­tein that plays an im­por­tant role in the sur­vival of plasma cells and is ex­pressed on mul­ti­ple myeloma cells.1

Dr Brian G.M. Durie, Chairman of the Board of the Inter­na­tional Myeloma Foundation, said: “The EC ap­prov­al of BLEN­REP is good news for patients with re­frac­tory mul­ti­ple myeloma whose can­cer con­tinues to progress and are in dire need of new treat­ment op­tions. We ap­pre­ci­ate GSK’s efforts to bring this new ther­apy to patients in the EU and for the com­mitment to addressing the needs of the mul­ti­ple myeloma com­munity.”

BLENREP was granted PRIME desig­na­tion in 2017 and the Conditional Marketing Autho­ri­sa­tion Appli­ca­tion was re­viewed under Euro­pean Medicines Agency’s ac­cel­er­ated assess­ment pro­ce­dure, which is given if the EMA’s Com­mit­tee for Medicinal Products for Human Use de­ter­mines the treat­ment is of major interest from a pub­lic health per­spec­tive and rep­re­sents a thera­peutic inno­va­tion.

Earlier this month, the US Food and Drug Admin­istra­tion ap­prov­ed BLEN­REP as a mono­therapy treat­ment for adult patients with re­lapsed or re­frac­tory mul­ti­ple myeloma who have re­ceived at least four prior ther­a­pies in­clud­ing an anti-CD38 mono­clonal anti­body, a pro­te­a­some in­hib­i­tor and an immuno­modu­la­tory agent, fol­low­ing a priority re­view for the com­pany’s Biologics License Appli­ca­tion.

About DREAMM-2

DREAMM-2 is an open label study of BLEN­REP. Patients in the trial had actively pro­gress­ing mul­ti­ple myeloma that had worsened de­spite cur­rent stan­dard of care and were ran­domised to two arms to re­ceive either 2.5 mg/kg or 3.4 mg/kg BLEN­REP Q3W. Over­all, patients in DREAMM-2 had more ad­vanced dis­ease, poorer prog­nosis and per­for­mance status and also had a greater num­ber of prior lines of ther­apy in comparison with patients in DREAMM-1, the first time in human study of BLEN­REP.

About mul­ti­ple myeloma

There are approx­i­mately 48,000 new cases of mul­ti­ple myeloma diag­nosed each year across Europe.2 Re­search into new treat­ments is needed as most patients will relapse or be­come re­frac­tory to avail­able ther­a­pies.3

About B-cell maturation an­ti­gen (BCMA)

The nor­mal function of BCMA is to promote plasma cell sur­vival by transduction of signals from two known ligands, BAFF (B-cell activating factor) and APRIL (a pro­lif­er­a­tion-inducing ligand). This path­way has been shown to be im­por­tant for myeloma cell growth and sur­vival. BCMA ex­pres­sion is lim­ited to B cells at later stages of de­vel­op­ment. BCMA is ex­pressed at varying levels in myeloma patients and BCMA membrane ex­pres­sion is universally detected in myeloma cell lines.4

About BLEN­REP

BLENREP is an anti­body drug con­ju­gate comprising a humanised anti-B cell maturation an­ti­gen (BCMA) mono­clonal anti­body con­ju­gated to the cyto­toxic agent auristatin F via non-cleavable linker. The drug linker tech­nology is licensed from Seattle Genetics; mono­clonal anti­body is pro­duced using POTELLIGENT Technology licensed from BioWa.

Important in­for­ma­tion for BLEN­REP in the EU

Indication

BLENREP is in­di­cated 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.

Important safety in­for­ma­tion

Contraindications: Hypersensitivity to the active sub­stance or to any of the excipients

Warnings and precautions: Corneal ad­verse re­ac­tions have been re­ported with BLEN­REP (kera­top­athy or microcyst-like epithelial changes in corneal epithelium with or without changes in visual acuity, blurred vision, and dry eye symp­toms). Ophthalmic examinations in­clud­ing assess­ment of visual acuity and slit lamp examination, should be per­formed at base­line, be­fore the sub­se­quent 3 treat­ment cycles and during treat­ment as clin­i­cally in­di­cated. Patients experiencing corneal ad­verse re­ac­tions may re­quire dose mod­i­fi­ca­tions or treat­ment dis­con­tinu­a­tion based on se­ver­i­ty of findings. Cases of corneal ulcer (ulcerative and infective ker­a­ti­tis) have been re­ported with BLEN­REP. These should be man­aged promptly and treat­ment with BLEN­REP should be in­ter­rupted until the corneal ulcer has healed. Due to the risk of thrombocytopenic events, com­plete blood counts should be ob­tained at base­line and monitored during treat­ment. Patients on con­com­i­tant anticoagulant treat­ments may re­quire more fre­quent monitoring and should be man­aged with a dose delay or re­duc­tions. If a mod­er­ate or severe in­fusion-related re­ac­tion oc­curs, in­ter­rupt in­fusion and provide sup­port­ive treat­ment. Once symp­toms re­solve, resume at a lower in­fusion rate. If anaphylactic or life-threatening in­fusion re­ac­tion, BLEN­REP should be per­ma­nently dis­con­tinued.

Undesirable effects: The most commonly-reported ad­verse re­ac­tions were ker­a­top­a­thy and thrombo­cyto­penia. The most commonly re­ported serious ad­verse re­ac­tions were pneu­monia, pyrexia and in­fusion re­lated re­ac­tions.

Very common (≥1/10): Pneumonia, thrombo­cyto­penia, anaemia, lymphopenia, leu­ko­penia, neu­tro­penia, ker­a­top­a­thy, blurred vision events, dry eye, nausea, diarrhoea, pyrexia, fatigue, in­creased aspartate amino­trans­ferase, in­creased gamma glutamyltransferase and in­fusion re­lated re­ac­tions.

Common (≥1/1000 to <1/10): Upper res­pira­tory tract in­for­ma­tion, photophobia, eye irritation, vomiting and in­creased creatine phosphokinase

Refer to the BLEN­REP Prescribing In­for­ma­tion for a full list of ad­verse events and the com­plete im­por­tant safety in­for­ma­tion.

GSK in Oncology

GSK is focused on maximising patient sur­vival through trans­formational med­i­cines. GSK’s pipe­line is focused on immuno-oncology, cell ther­apy, can­cer epigenetics, and syn­thet­ic lethality. Our goal is to achieve a sustainable flow of new treat­ments based on a di­vers­i­fied port­folio of inves­ti­ga­tional med­i­cines utilising modalities such as small mol­e­cules, anti­bodies, anti­body drug con­ju­gates and cells, either alone or in com­bi­na­tion.

About GSK

GSK is a science-led global health­care com­pany with a spe­cial pur­pose: to help people do more, feel better, live longer. For fur­ther in­for­ma­tion please visit www.gsk.com/about-us.

Cautionary state­ment re­gard­ing for­ward-looking state­ments

GSK cautions in­vestors that any for­ward-looking state­ments or pro­jec­tions made by GSK, in­clud­ing those made in this an­nouncement, are subject to risks and un­cer­tainties that may cause actual re­­sults to differ ma­teri­ally from those pro­jected. Such factors in­clude, but are not lim­ited to, those described under Item 3.D "Risk Factors" in the com­pany's Annual Report on Form 20-F for 2019 and as set out in GSK’s “Principal risks and un­cer­tainties” section of the Q2 Results and any im­pacts of the COVID-19 pan­dem­ic.

References

  1. Trudel S, Lendvai N, Popat R, et al. Anti­body–drug con­ju­gate, GSK2857916, in re­lapsed / refractory mul­ti­ple myeloma: an up­date on safety and ef­fi­cacy from dose ex­pan­sion phase I study. Blood Cancer Journal. 2019;9(4). DOI:10.1038/s41408-019-0196-6.
  2. Multiple Myeloma. World Health Or­ga­ni­za­tion Inter­na­tional Agency for Re­search on Cancer. https://gco.iarc.fr/today/data/factsheets/cancers/35-Multiple-myeloma-fact-sheet.pdf. Accessed August 2020.
  3. Nooka A, Kastritis E, Dimopoulos M, Lonial S. Treatment op­tions for re­lapsed and re­frac­tory mul­ti­ple myeloma. Blood. 2015;125(20):3085-3099. DOI:10.1182/blood-2014-11-568923.
  4. Lonial, S, et al. Be­lan­ta­mab mafo­dotin for re­lapsed or re­frac­tory mul­ti­ple myeloma (DREAMM-2): a two-arm, ran­domised, open-label, phase 2 study. Lancet Oncol. 2020; 21(2):207–21.

Source: GlaxoSmithKline.

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