FDA approves GSK?s BLENREP (belantamab mafodotin-blmf) for the treatment of patients with relapsed or refractory multiple myeloma
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 characterised 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 programme 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.
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 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.iii
About BLENREP (belantamab mafodotin-blmf)
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 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:
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. |
- 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.