The European Commission has approved an expanded indication for melphalan flufenamide, allowing the treatment to be used earlier in patients with relapsed or refractory multiple myeloma. The decision marks a significant regulatory milestone for Swedish biotechnology company Oncopeptides, potentially broadening treatment options for patients who have already received multiple therapies.
Announced on November 9, 2026, the approval extends the use of melphalan flufenamide in combination with dexamethasone to patients who have received at least two prior lines of treatment, moving the therapy from the fourth-line setting into third-line treatment and beyond.
Importantly, the expanded indication removes the previous requirement for patients to be refractory to three major classes of myeloma therapies.
What Changes Under the New Melphalan Flufenamide Approval?
Previously, melphalan flufenamide was authorized in Europe for patients who had received at least three prior lines of therapy and met the criteria for triple-class refractory disease.
Under the newly approved indication, melphalan flufenamide plus dexamethasone can be prescribed to adults with multiple myeloma who:
- Have received at least two prior lines of therapy.
- Have disease refractory to lenalidomide and their most recent line of treatment.
- If previously treated with autologous stem cell transplantation, experienced disease progression at least three years after transplantation.
This change allows clinicians to consider melphalan flufenamide earlier, without waiting for patients to develop resistance to all three major treatment classes.
The decision formally confirms the positive opinion issued by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP).
Clinical Evidence Behind the Expanded Indication
The expanded approval is supported by clinical evidence from the Phase 3 OCEAN trial, alongside safety information from other clinical studies and real-world experience.
OCEAN evaluated melphalan flufenamide plus dexamethasone against pomalidomide plus dexamethasone in 495 patients with relapsed or refractory multiple myeloma who had received two to four previous treatment lines.
The trial reported a median progression-free survival of 6.8 months with melphalan flufenamide compared with 4.9 months with pomalidomide.
However, overall survival was not improved in the overall trial population, with median overall survival of approximately 19.8 months versus 25.0 months, respectively. Hematologic toxicity was also substantial.
The European regulatory assessment considered the benefit-risk profile in the defined eligible population, particularly the restriction concerning patients with prior autologous stem cell transplantation.
Melphalan flufenamide is a peptide-drug conjugate containing an alkylating agent designed to deliver cytotoxic activity into cancer cells. Important adverse effects include thrombocytopenia, neutropenia, anemia, and infections.
Oncopeptides Expects Expanded Access Across Europe
According to Oncopeptides, removing the triple-class refractory requirement could approximately double the eligible patient population for melphalan flufenamide across Europe.
The company also expects patients treated in the third-line setting to receive approximately twice as many treatment cycles, on average, compared with patients treated in the previous fourth-line setting.
Sofia Heigis, CEO of Oncopeptides, emphasized the significance of the decision:
“While this formal decision was anticipated following CHMP’s recommendation, its strategic importance cannot be overstated.”
Beyond its clinical implications, the expanded indication is expected to support the company’s commercial growth and its objective of achieving positive cash flow during 2027.
What Happens Next Across Europe?
Following the approval, Oncopeptides is preparing to expand access to melphalan flufenamide across its European markets.
In Germany, the company plans to submit a market access dossier within approximately one month, enabling commercial sales under the expanded indication while health technology assessment and pricing negotiations proceed.
In Spain and Italy, local pricing and reimbursement procedures will follow their respective national timelines. The company is also evaluating opportunities in additional European markets.
Although the European Commission’s authorization broadens the approved indication, actual patient access will depend on national reimbursement arrangements and local clinical practice.
What Does This Mean for Multiple Myeloma Treatment?
The expanded European approval comes against a complex regulatory history for melphalan flufenamide.
In February 2024, the US Food and Drug Administration withdrew its approval after concluding that the confirmatory study had not verified clinical benefit and that the available evidence did not establish safety and effectiveness under its US conditions of use.
European regulators reached a different benefit-risk conclusion for a more specifically defined patient population, including restrictions related to prior transplantation.
The November 2026 decision broadens that European indication, making melphalan flufenamide available for consideration earlier in the treatment pathway.
For patients with relapsed or refractory multiple myeloma, whose disease frequently requires successive lines of therapy, the approval adds another authorized treatment option. Its place alongside newer immunotherapies and other available regimens will depend on patient selection, clinical outcomes, tolerability, and access.
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