The U.S. Food and Drug Administration‘s (FDA) Oncologic Drugs Advisory Committee (ODAC) has voted 12-0 in favor of positive benefit/risk profile for belantamab mafodotin (previously known as GSK2857916) for the treatment of patients with relapsed/refractory multiple myeloma.
The advisory committee believes that the demonstrated benefit of monotherapy treatment with belantamab mafodotin outweighing the risks for patients with relapsed or refractory multiple myeloma who have received at least four prior therapies including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.
Two committee members could not participate in the final vote.
Belantamab mafodotin is an investigational antibody-drug conjugate or ADC which includes a humanized anti-B cell maturation antigen (BCMA) monoclonal antibody (mAb) produced using POTELLIGENT Technology licensed from BioWa, conjugated to the cytotoxic agent monomethyl auristatin F via a non-cleavable linker, licensed from Seattle Genetics.
Multiple myeloma is the second most common blood cancer in the US and is generally considered treatable, but not curable.[1] Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments. [2]
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. [2]
First-in-class anti-BCMA therapy
A spokesperson for GlaxoSmithKline Pharmaceuticals (GSK) said it looks forward to working with the FDA as they complete their review of the Biologics License Application. In addition, the spokesperson confirmed that if approved, belantamab mafodotin will be a first-in-class anti-BCMA therapy for the treatment of relapsed/refractory multiple myeloma.
“We are pleased the committee recognized the potential for belantamab mafodotin to help patients who have relapsed or refractory multiple myeloma, an incurable disease with limited treatment options. We look forward to working with the FDA as they complete their review of our Biologics License Application,” said Axel Hoos, M.D., Ph.D., Senior Vice President and Head of Oncology R&D, GSK.
DREAMM clinical development program
The recommendation was based on data from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical trial program, including the pivotal DREAMM-2 study which enrolled heavily pre-treated patients who had actively progressing multiple myeloma that had worsened despite current standard of care.[3] The six-month primary results from the study were published in The Lancet Oncology in December 2019 and serve as the basis for the Biologics License Application (BLA).
Adverse events
During the review process, the FDA reviewers had asked questions about observed side effects seen with belantamab mafodotin, including an eye-related adverse event that led to declines in visual acuity. The investigators proposed dose modifications to counter the observed risk, however, the reviewers noted that some patients in clinical trials still had unresolved eye problems even after dose modifications.
Next steps
The FDA will consider the recommendation of the committee. However, the regulatory agency is not obligated to follow it. Warlier in the development of the investigational agent, The FDA granted breakthrough therapy designation to belantamab mafodotin (2017) and priority review designation for the BLA earlier this year.
A Marketing Authorisation Application for belantamab mafodotin also is under accelerated assessment by the European Medicines Agency (EMA)
Clinical trials
A Study to Investigate the Efficacy and Safety of Two Doses of GSK2857916 in Participants With Multiple Myeloma Who Have Failed Prior Treatment With an Anti-CD38 Antibody – NCT03525678
Reference
[1] Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol. 2016;43(6):676–681. doi:10.1053/j.seminoncol.2016.11.004.
[2] 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.
[3] Lonial, S, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomized, open-label, phase 2 study. Lancet Oncol. 2020; 21(2):207–21.
[4] Dosio, F.; Brusa, P.; Cattel, L. Immunotoxins and Anticancer Drug Conjugate Assemblies: The Role of the Linkage between Components”. Toxins. 3 (12): 848–883. doi:10.3390/toxins3070848.
