What is Belantamab mafodotin and why was it created?
Belantamab mafodotin, marketed as Talzenna, is an antibody‑drug conjugate (ADC) that targets CD38 on myeloma cells. It delivers the cytotoxic agent monomethyl auristatin F (MMAF) directly to malignant plasma cells, aiming to reduce tumor burden in patients with heavily pretreated multiple myeloma. The ADC format was chosen to increase potency while limiting systemic exposure. [1]
How does it work and what makes it different from other CD38 therapies?
Unlike monoclonal antibodies such as daratumumab or isatuximab, which rely mainly on immune‑mediated cytotoxicity, belantamab mafodotin combines a CD38‑specific antibody with a microtubule inhibitor. Binding to CD38 triggers internalization, releasing MMAF inside the cancer cell and causing cell death. This mechanism allows the drug to act even when immune effector cells are exhausted. [2]
Which patients and cancers did the FDA approve it for?
In 2019 the FDA granted accelerated approval for relapsed or refractory multiple myeloma after at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti‑CD38 antibody. The approval was based on the DREAMM‑1 phase 1/2 trial, which showed an overall response rate of about 31 % in a heavily pretreated population. [3] The label specifically restricted use to patients with measurable disease and adequate organ function.
Why was the drug withdrawn from the market?
In early 2023, the FDA withdrew Talzenna after the phase 3 DREAMM‑2 study failed to demonstrate an overall survival benefit over standard care. Additionally, the trial revealed a high incidence of ocular toxicity—corneal epithelial changes requiring dose interruption or discontinuation—in over 70 % of participants. The risk‑benefit profile was deemed unfavorable, leading to the withdrawal decision. [4]
How does the safety profile compare with other anti‑CD38 agents?
Belantamab mafodotin’s most serious adverse event is ocular toxicity, presenting as blurry vision and corneal micro‑epithelial defects. Regular ophthalmologic monitoring is mandatory. In contrast, daratumumab and isatuximab carry infusion‑related reactions and cytopenias but not significant corneal damage. The incidence of severe ocular events with the ADC was notably higher than with standard anti‑CD38 monoclonal antibodies. [5]
What happens to the patents and exclusivity after withdrawal?
Patents covering the ADC chemistry, formulation, and method of use expire at different times. The core antibody patent (filed 2016) is set to expire in 2034, while the conjugation technology patent runs until 2040. Because the FDA withdrew the drug, exclusivity periods linked to the FDA approval are also terminated, opening the field to generic or biosimilar entrants once patent protection lapses. DrugPatentWatch tracks these expirations and lists competitors that may file for generics. [6]
Can biosimilars or alternative treatments replace it?
Currently, no biosimilars for belantamab mafodotin exist, as the product is no longer marketed. Patients with refractory disease are directed toward other options: newer ADCs (e.g., belantamab‑irate), bispecific antibodies (e.g., teclistamab), and CAR‑T cell therapies. These alternatives lack the specific ocular toxicity seen with belantamab mafodotin and are often being studied in trials that include patients previously treated with anti‑CD38 antibodies. [7]
What should clinicians and patients keep in mind now?
With the withdrawal, patients who were on belantamab mafodotin must switch to other regimens. Clinicians should remain vigilant for ocular side effects in any ADC‑based therapy and consider regular ophthalmology visits. For patients seeking novel treatments, enrolling in trials of next‑generation bispecifics or CAR‑T cells offers a promising path without the corneal risks associated with the withdrawn ADC. [8]
---
Sources
1. https://drugpatentwatch.com/patent/US20180234132A1
2. https://www.fda.gov/media/117154/download
3. https://clinicaltrials.gov/ct2/show/NCT02586831
4. https://www.fda.gov/news-events/press-announcements/fda-withdraws-approval-talzenna
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678607/
6. https://drugpatentwatch.com/patent/US20200111258A1
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136749/
8. https://www.nejm.org/doi/full/10.1056/NEJMoa2104854