• BLENREP is a first-in-class anti-BCMA (B-cell maturation an­ti­gen) ther­apy for patients whose dis­ease has progressed de­spite prior treat­ment with an immuno­modu­la­tory agent, pro­te­a­some in­hib­i­tor and anti-CD38 anti­body
• BLENREP is the fifth major med­i­cine ap­prov­al for GSK in 2020

London, United Kingdom (Press Release) – GlaxoSmithKline plc (LSE/NYSE: GSK) an­nounced the US Food and Drug Admin­istra­tion (FDA) has approved BLEN­REP (belantamab mafo­dotin-blmf) 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. This in­di­ca­tion is approved under ac­cel­er­ated ap­prov­al based on re­sponse rate. Continued ap­prov­al for this in­di­ca­tion may be con­tin­gent upon veri­fi­ca­tion and description of clin­i­cal ben­e­fit in con­firmatory trials. BLEN­REP is the first anti-BCMA (B-cell maturation an­ti­gen) ther­apy approved any­where in the world.¹

Dr. Hal Barron, Chief Scientific Of­fi­cer and Pres­i­dent R&D, GSK, said: “As the sec­ond most common form of blood can­cer in the US, mul­ti­ple myeloma is an incurable and dev­as­tat­ing dis­ease. BLEN­REP is the first approved anti-BCMA ther­apy and has the po­ten­tial to trans­form the treat­ment of patients with re­lapsed or re­frac­tory myeloma who have lim­ited treat­ment op­tions to­day.’’

BLENREP is GSK’s fifth major med­i­cine ap­prov­al in 2020 across areas of sig­nif­i­cant unmet med­i­cal need such as can­cer, HIV and chronic kidney dis­ease. This ap­prov­al marks the sec­ond FDA ap­prov­al for GSK’s on­col­ogy port­folio in four months.

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.² The ap­prov­al of BLEN­REP was based on six-month pri­mary re­­sults from the pivotal DREAMM-2 study, which en­rolled patients with re­lapsed or re­frac­tory mul­ti­ple myeloma who had actively pro­gress­ing dis­ease that had worsened de­spite cur­rent stan­dard of care.

Dr. Sagar Lonial, MD, Chief Medical Of­fi­cer, Winship Cancer In­sti­tute of Emory Uni­ver­sity in Atlanta, Georgia, Chair of Emory De­part­ment of He­ma­tol­ogy and Medical Oncology and Prin­ci­pal In­ves­ti­ga­tor for DREAMM-2, said: “While treatable, re­frac­tory mul­ti­ple myeloma is a sig­nif­i­cant clin­i­cal chal­lenge with poor out­comes for patients whose dis­ease has be­come re­sis­tant to the cur­rent stan­dard of care. Due to the lim­ited op­tions cur­rently avail­able, these patients are often retreated with drugs from the same classes after they relapse, which is why the ap­prov­al of BLEN­REP, the first anti-BCMA ther­apy, is sig­nif­i­cant for both patients and physicians alike.”

In the DREAMM-2 study, treat­ment with single-agent BLEN­REP 2.5 mg/kg every three weeks dem­onstrated a clin­i­cally meaningful over­all re­sponse rate (ORR) of 31% (97.5% CI; 21-43) in patients who had re­ceived a median of seven prior lines of treat­ment (n=97). The median duration of re­sponse (DoR) had not been reached at the six-month analysis, but 73% of responders had a DoR equal to or greater than six months. The most commonly re­ported ad­verse events (≥20%) were ker­a­top­a­thy, de­creased visual acuity, nausea, blurred vision, pyrexia, in­fusion-related reac­tions, and fatigue. Ker­a­top­a­thy is char­ac­ter­ized as changes in the corneal epithelium as seen on eye examination, which can manifest with or without symp­toms.

Ocular ad­verse reac­tions oc­curred in 77% of the 218 patients in the pooled safety pop­u­la­tion and in­cluded ker­a­top­a­thy (76%), changes in visual acuity (55%), blurred vision (27%), and dry eye (19%). Corneal ad­verse events were monitored with eye exams prior to each dose, allow­ing for dose re­duc­tions or in­ter­rup­tions as appro­pri­ate. Patients also used preservative-free eye drops. Ker­a­top­a­thy lead­ing to treat­ment dis­con­tinu­a­tion affected 2.1% of patients in the 2.5 mg/kg cohort.³

BLENREP is avail­able through par­tic­i­pa­tion in the BLEN­REP Risk Evaluation and Mitigation Strategy (REMS), which was devel­oped to ensure appro­pri­ate use of the med­i­cine. The pro­gram re­quires education for all physicians pre­scrib­ing BLEN­REP and their patients re­gard­ing the oc­u­lar risks asso­ci­ated with treat­ment as well as monitoring. Addi­tional in­for­ma­tion about the BLEN­REP REMS can be found at www.blenreprems.com or 1-855-209-9188.

Paul Giusti, Pres­i­dent and CEO of the Multiple Myeloma Re­search Foundation (MMRF), said: “The ap­prov­al of BLEN­REP is an im­por­tant ad­vancement for patients with re­lapsed or re­frac­tory mul­ti­ple myeloma, as it brings a much-needed new treat­ment to patients who face lim­ited op­tions due to their pro­gress­ing dis­ease. We are grateful for GSK’s con­tinued com­mitment to myeloma patients and their families.”

In 2017, BLEN­REP was granted Break­­through Therapy desig­na­tion by the FDA, which is in­tended to facilitate the de­vel­op­ment of inves­ti­ga­tional med­i­cines that have shown clin­i­cal prom­ise for con­di­tions where there is sig­nif­i­cant unmet need.

Making Our Products Affordable and Accessible

GSK is actively in­volved in creating solu­tions that allow patients to have access to new scientific break­­throughs. We re­main com­mit­ted to helping patients access GSK med­i­ca­tions and have a long history of providing patient assistance pro­grams. Patients and health­care professionals can access more in­for­ma­tion about our on­col­ogy spe­cif­ic resources on insurance coverage and fi­nan­cial sup­port at: www.TogetherwithGSKOncology.com or call: 1-844-4GSK-ONC (1-844-447-5662).

About Multiple Myeloma

Multiple myeloma is the sec­ond most common blood can­cer in the US and is generally con­sidered treatable, but not curable.⁴ In the US, more than 32,000 people are esti­mated to be diag­nosed with mul­ti­ple myeloma this year and nearly 13,000 people will die from the dis­ease.⁵ Re­search into new ther­a­pies is needed as mul­ti­ple myeloma commonly be­comes re­frac­tory to avail­able treat­ments.⁶

About BLEN­REP (belantamab mafo­dotin-blmf)

BLENREP is an anti­body drug con­ju­gate comprising a humanized 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 SAFETY INFORMATION FOR BLEN­REP

WARNINGS AND PRECAUTIONS

Ocular Toxicity: Ocular ad­verse reac­tions oc­curred in 77% of the 218 patients in the pooled safety pop­u­la­tion. Ocular ad­verse reac­tions in­cluded ker­a­top­a­thy (76%), changes in visual acuity (55%), blurred vision (27%), and dry eye (19%). Among patients with ker­a­top­a­thy (n = 165), 49% had oc­u­lar symp­toms, 65% had clin­i­cally relevant visual acuity changes (decline of 2 or more lines on Snellen Visual Acuity in any eye), and 34% had both oc­u­lar symp­toms and visual acuity changes.

Keratopathy: Ker­a­top­a­thy was re­ported as Grade 1 in 7% of patients, Grade 2 in 22%, Grade 3 in 45%, and Grade 4 in 0.5% per the KVA scale. Cases of corneal ulcer (ulcerative and infective ker­a­ti­tis) have been re­ported. Most ker­a­top­a­thy events devel­oped within the first 2 treat­ment cycles (cumulative in­ci­dence of 65% by Cycle 2). Of the patients with Grade 2 to 4 ker­a­top­a­thy (n = 149), 39% recovered to Grade 1 or lower after median follow-up of 6.2 months. Of the 61% who had on­go­ing ker­a­top­a­thy, 28% were still on treat­ment, 9% were in follow-up, and in 24% the follow-up ended due to death, study withdrawal, or lost to follow-up. For patients in whom events re­solved, the median time to resolution was 2 months (range: 11 days to 8.3 months).

Visual Acuity Changes: A clin­i­cally sig­nif­i­cant de­crease in visual acuity of worse than 20/40 in the better-seeing eye was ob­served in 19% of the 218 patients and of 20/200 or worse in the better-seeing eye in 1.4%. Of the patients with de­creased visual acuity of worse than 20/40, 88% re­solved and the median time to resolution was 22 days (range: 7 days to 4.2 months). Of the patients with de­creased visual acuity of 20/200 or worse, all re­solved and the median duration was 22 days (range: 15 to 22 days).

Monitoring and Patient Instruction: Conduct ophthalmic examinations (visual acuity and slit lamp) at base­line, prior to each dose, and promptly for worsening symp­toms. Perform base­line examinations within 3 weeks prior to the first dose. Perform each follow-up examination at least 1 week after the pre­vi­ous dose and within 2 weeks prior to the next dose. Withhold BLEN­REP until im­prove­ment and resume at same or reduced dose, or con­sider per­ma­nently dis­con­tin­u­ing based on se­ver­i­ty. Advise patients to use preservative-free lubricant eye drops at least 4 times a day start­ing with the first in­fusion and continuing until end of treat­ment. Avoid use of contact lenses unless directed by an oph­thal­mol­o­gist. Changes in visual acuity may be asso­ci­ated with dif­fi­culty for driving and reading. Advise patients to use caution when driving or op­er­at­ing machinery. BLEN­REP is only avail­able through a restricted pro­gram under a REMS.

BLENREP REMS: BLEN­REP is avail­able only through a restricted pro­gram under a REMS called the BLEN­REP REMS because of the risks of oc­u­lar toxicity. Notable re­quire­ments of the BLEN­REP REMS in­clude the fol­low­ing:

• Prescribers must be certified with the pro­gram by en­rolling and com­plet­ing training in the BLENREP REMS.
• Prescribers must counsel patients re­ceiv­ing BLENREP about the risk of ocular toxicity and the need for ophthalmic examinations prior to each dose.
• Patients must be en­rolled in the BLENREP REMS and comply with monitoring.
• Healthcare facilities must be certified with the pro­gram and verify that patients are authorized to re­ceive BLENREP.
• Wholesalers and distributers must only distribute BLENREP to certified health­care facilities.

Further in­for­ma­tion is avail­able at www.BLENREPREMS.com and 1-855-209-9188.

Thrombocytopenia: Thrombocytopenia oc­curred in 69% of 218 patients in the pooled safety pop­u­la­tion, in­clud­ing Grade 2 in 13%, Grade 3 in 10%, and Grade 4 in 17%. The median time to onset of the first thrombocytopenic event was 26.5 days. Thrombocytopenia re­­sulted in dose re­duc­tion, dose in­ter­rup­tion, or dis­con­tinu­a­tion in 9%, 2.8%, and 0.5% of patients, re­spec­tively. Grade 3 to 4 bleeding events oc­curred in 6% of patients, in­clud­ing Grade 4 in 1 patient. Fatal ad­verse reac­tions in­cluded cerebral hemorrhage in 2 patients. Perform com­plete blood cell counts at base­line and during treat­ment as clin­i­cally in­di­cated. Consider withholding and/or reducing the dose based on se­ver­i­ty.

Infusion-Related Reactions: Infusion-related reac­tions oc­curred in 18% of 218 patients in the pooled safety pop­u­la­tion, in­clud­ing Grade 3 in 1.8%. Monitor patients for in­fusion-related reac­tions. For Grade 2 or 3 reac­tions, in­ter­rupt the in­fusion and provide sup­port­ive treat­ment. Once symp­toms re­solve, resume at a lower in­fusion rate. Ad­min­ister premedication for all sub­se­quent in­fusions. Dis­con­tinue BLEN­REP for life-threatening in­fusion-related reac­tions and provide appro­pri­ate emer­gen­cy care.

Embryo-Fetal Toxicity: Based on its mech­a­nism of action, BLEN­REP can cause fetal harm when admin­istered to a pregnant woman because it con­tains a genotoxic com­pound (the microtubule in­hib­i­tor, monomethyl auristatin F [MMAF]) and it targets actively dividing cells. Advise pregnant women of the po­ten­tial risk to a fetus. Advise females of reproductive po­ten­tial to use ef­fec­tive con­tra­cep­tion during treat­ment with BLEN­REP and for 4 months after the last dose. Advise males with female part­ners of reproductive po­ten­tial to use ef­fec­tive con­tra­cep­tion during treat­ment with BLEN­REP and for 6 months after the last dose.

ADVERSE REACTIONS

The pooled safety pop­u­la­tion described in Warnings and Precautions reflects exposure to BLEN­REP at a dosage of 2.5 mg/kg or 3.4 mg/kg (1.4 times the rec­om­mended dose) admin­istered in­tra­venously once every 3 weeks in 218 patients in DREAMM-2. Of these patients, 194 re­ceived a liquid for­mu­la­tion (not the approved dosage form) rather than the lyophilized powder. Among the 218 patients, 24% were exposed for 6 months or longer.

The safety of BLEN­REP as a single agent was eval­u­ated in DREAMM-2. Patients re­ceived BLEN­REP at the rec­om­mended dosage of 2.5 mg/kg admin­istered in­tra­venously once every 3 weeks (n = 95). Among these patients, 22% were exposed for 6 months or longer.

Serious ad­verse reac­tions oc­curred in 40% of patients who re­ceived BLEN­REP. Serious ad­verse reac­tions in >3% of patients in­cluded pneu­monia (7%), pyrexia (6%), renal im­pair­ment (4.2%), sepsis (4.2%), hypercalcemia (4.2%), and in­fusion-related reac­tions (3.2%). Fatal ad­verse reac­tions oc­curred in 3.2% of patients, in­clud­ing sepsis (1%), cardiac arrest (1%), and lung in­fec­tion (1%).

Permanent dis­con­tinu­a­tion due to an ad­verse reac­tion oc­curred in 8% of patients who re­ceived BLEN­REP; ker­a­top­a­thy (2.1%) was the most fre­quent ad­verse reac­tion re­­sult­ing in per­ma­nent dis­con­tinu­a­tion.

Dosage in­ter­rup­tions due to an ad­verse reac­tion oc­curred in 54% of patients who re­ceived BLEN­REP. Adverse reac­tions which re­quired a dosage in­ter­rup­tion in >3% of patients in­cluded ker­a­top­a­thy (47%), blurred vision (5%), dry eye (3.2%), and pneu­monia (3.2%).

Dose re­duc­tions due to an ad­verse reac­tion oc­curred in 29% of patients. Adverse reac­tions which re­quired a dose re­duc­tion in >3% of patients in­cluded ker­a­top­a­thy (23%) and thrombo­cyto­penia (5%). The most common ad­verse reac­tions (≥20%) were ker­a­top­a­thy (71%), de­creased visual acuity (53%), nausea (24%), blurred vision (22%), pyrexia (22%), in­fusion-related reac­tions (21%), and fatigue (20%). The most common Grade 3 or 4 (≥5%) laboratory ab­nor­mal­i­ties were lym­pho­cytes de­creased (22%), plate­lets de­creased (21%), hemoglobin de­creased (18%), neu­tro­phils de­creased (9%), cre­at­i­nine in­creased (5%), and gamma-glutamyl transferase in­creased (5%).

USE IN SPECIFIC POPULATIONS

Lactation: There is no data on the presence of be­lan­ta­mab mafo­dotin-blmf in human milk or the effects on the breastfed child or milk pro­duc­tion. Because of the po­ten­tial for serious ad­verse reac­tions in the breastfed child, advise women not to breastfeed during treat­ment with BLEN­REP and for 3 months after the last dose.

Females and Males of Reproductive Potential: BLEN­REP can cause fetal harm when admin­istered to pregnant women. There are no avail­able data on the use of BLEN­REP in pregnant women to eval­u­ate for drug-associated risk. No animal reproduction stud­ies were con­ducted with BLEN­REP.

Pregnancy Testing: Pregnancy testing is rec­om­mended for females of reproductive po­ten­tial prior to initiating BLEN­REP.

Infertility: Based on findings in animal stud­ies, BLEN­REP may im­pair fertility in females and males. The effects were not reversible in male rats but were reversible in female rats.

Geriatric Use: Of the 218 patients who re­ceived BLEN­REP in DREAMM-2, 43% were aged 65 to less than 75 years and 17% were aged 75 years and older. Ker­a­top­a­thy oc­curred in 80% of patients aged less than 65 years and 73% of patients aged 65 years and older. Among the patients who re­ceived BLEN­REP at the 2.5-mg/kg dose in DREAMM-2 (n = 95), ker­a­top­a­thy oc­curred in 67% of patients aged less than 65 years and 73% of patients aged 65 years and older.

Renal Impairment: No dose ad­just­ment is rec­om­mended for patients with mild or mod­er­ate renal im­pair­ment (estimated glomerular filtration rate [eGFR] 30 to 89 mL/min/1.73m2 as esti­mated by the Modification of Diet in Renal Disease [MDRD] equation). The rec­om­mended dosage has not been estab­lished in patients with severe renal im­pair­ment (eGFR 15 to 29 mL/min/1.73 m2) or end-stage renal dis­ease (ESRD) with eGFR <15 mL/min/1.73 m2 not on dialysis or re­quir­ing dialysis.

Hepatic Impairment: No dose ad­just­ment is rec­om­mended for patients with mild hepatic im­pair­ment (total bil­i­ru­bin ≤upper limit of nor­mal [ULN] and aspartate amino­trans­ferase (AST) >ULN or total bil­i­ru­bin 1 to ≤1.5 × ULN and any AST). The rec­om­mended dosage of BLEN­REP has not been estab­lished in patients with mod­er­ate or severe hepatic im­pair­ment (total bil­i­ru­bin >1.5 × ULN and any AST).

INDICATION

BLENREP is in­di­cated for the treat­ment of adults 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.

This in­di­ca­tion is approved under ac­cel­er­ated ap­prov­al based on re­sponse rate. Continued ap­prov­al for this in­di­ca­tion may be con­tin­gent upon veri­fi­ca­tion and description of clin­i­cal ben­e­fit in a con­firmatory trial(s).

The full Prescribing In­for­ma­tion, in­clud­ing BOXED WARNING and Medication Guide, is avail­able here:

https://gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Blenrep/pdf/BLENREP-PI-MG.PDF

GSK in Oncology

GSK is focused on maximizing 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 uti­liz­ing 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. NCI Drug Dictionary - Anti-BCMA Anti­body-Drug Conjugate GSK2857916. National Cancer In­sti­tute. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/anti-bcma-antibody-drug-conjugate-gsk2857916. Accessed May 2020.
2. 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.
3. 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.
4. Estimated num­ber of incident cases world­wide, both sexes, all ages. World Health Or­ga­ni­za­tion. https://gco.iarc.fr/ Published 2020. Accessed May 2020.
5. SEER Cancer Facts & Figures 2019. Available at: https://seer.cancer.gov/statfacts/html/mulmy.html. Accessed De­cem­ber 19, 2019.
6. Nooka AK, Kastritis E, Dimopoulos MA. Treatment op­tions for re­lapsed and re­frac­tory mul­ti­ple myeloma. Blood. 2015;125(20)

Source: GlaxoSmithKline.