- 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
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.i
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.ii 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.iii
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.iv 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.v Research into new
therapies is needed as multiple myeloma commonly becomes refractory
to available treatments.vi
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
WARNING: OCULAR
TOXICITY
BLENREP caused changes
in the corneal epithelium resulting in changes in vision, including
severe vision loss and corneal ulcer, and symptoms such as blurred
vision and dry eyes.
Conduct ophthalmic exams at
baseline, prior to each dose, and promptly for worsening symptoms.
Withhold BLENREP until improvement and resume, or permanently
discontinue, based on severity.
Because of the risk of ocular
toxicity, BLENREP is available only through a restricted program
under a Risk Evaluation and Mitigation Strategy (REMS) called the
BLENREP REMS.
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, will be available here.
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.
Editor’s Note: In addition to the FDA’s approval of
BLENREP, GSK has received four major medicine approvals to date in
2020 for CABENUVA (cabotegravir and rilpivirine) in Canada, DUVROQ
(daprodustat) in Japan and ZEJULA (niraparib) and RUKOBIA
(fostemsavir) in the 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.
Registered in England & Wales: No. 3888792
Registered Office: 980 Great West Road Brentford,
Middlesex TW8 9GS
References ______________________ i 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. ii 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. iii 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. iv Estimated number of incident cases worldwide, both
sexes, all ages. World Health Organization. https://gco.iarc.fr/
Published 2020. Accessed May 2020. v SEER Cancer Facts &
Figures 2019. Available at:
https://seer.cancer.gov/statfacts/html/mulmy.html. Accessed
December 19, 2019. vi Nooka AK, Kastritis E, Dimopoulos MA.
Treatment options for relapsed and refractory multiple myeloma.
Blood. 2015;125(20)
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