GSK's efforts to reintroduce its antibody-drug conjugate Blenrep (belantamab mafodotin) to the U.S. market face significant regulatory hurdles as the FDA has raised serious concerns about the drug's eye safety profile. The agency's briefing document, released on July 15, highlights persistent ocular toxicity issues that will be central to an Oncologic Drugs Advisory Committee (ODAC) meeting on July 17.
FDA Identifies Unique Ocular Toxicity Profile
FDA reviewers flagged high rates of ocular toxicity, including corneal disease known as keratopathy and visual acuity changes. The agency noted that "while ocular adverse events have been seen with other antibody-drug conjugates used for the treatment of cancer, this toxicity is unique among therapies for the treatment of multiple myeloma."
The safety concerns stem from data in the pivotal DREAMM-7 (NCT04246047) and DREAMM-8 (NCT04484623) studies supporting Blenrep's approval application. FDA reviewers reported that the majority of patients in these trials experienced keratopathy and Visual Acuity (KVA) events, with all grade KVAs occurring in 92% and 93% of patients in DREAMM-7 and DREAMM-8, respectively. More concerning, serious grade 3-4 events were found in 77% and 78% of patients in the same two studies.
Market Impact and Regulatory Pathway
The FDA's concerns had immediate market consequences, with GSK shares closing 1.19% down to £1,402.5 following the briefing document release. The company's market capitalization stands at £57 billion, and prices had not recovered by the following market open.
GSK is seeking FDA approval for Blenrep in combination with Takeda's Velcade and dexamethasone to treat adults with multiple myeloma who have received one prior line of therapy. The company is also pursuing approval for the ADC in combination with Bristol Myers Squibb's Pomalyst and dexamethasone in the same patient population.
Regulatory History and Global Progress
Blenrep originally won FDA approval in 2020 to treat multiple myeloma but was withdrawn by GSK in 2022 after confirmatory trial shortcomings. Since then, the company has conducted additional trials to demonstrate the drug's effectiveness in treating the rare blood cancer.
Despite U.S. regulatory challenges, GSK has made progress in other markets. The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) issued a positive recommendation for Blenrep in May 2025, though the European Commission has not yet made a final approval decision. The UK became the first country to authorize Blenrep in the revised treatment setting in April 2025.
Commercial Expectations and Market Position
GSK has forecast more than £3 billion in peak annual sales for Blenrep, reflecting confidence in the broader ADC market momentum. However, GlobalData estimates predict more conservative peak sales of $1.9 billion through 2031.
In its own briefing document, GSK argued that results from DREAMM-7 and DREAMM-8 "consistently demonstrated meaningful benefit across endpoints and supported the positive benefit-risk of Blenrep." The company contends that the clinical data supports the drug's therapeutic value despite the ocular safety concerns.
The ODAC recommendation will be crucial for GSK's commercial projections, as the FDA typically follows advisory committee guidance when making approval decisions. The unique nature of Blenrep's eye safety profile among multiple myeloma treatments presents a particular challenge for the company's regulatory strategy.
