Melflufen (melphalan flufenamide) / Oncopeptides, SCBIO - LARVOL DELTA

European Journal of Haematology: Real-World Data reinforces Pepaxti’s role in treatment sequencing for multiple myeloma (Oncopeptides Press Release) - "The study, conducted at the IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy, confirms the efficacy and safety of Pepaxti (melflufen) plus dexamethasone. The heavily pretreated patients, including those refractory to novel immunotherapies, benefitted from Pepaxti’s strong efficacy, the overall response rate (ORR) was 41% with a median progression-free survival (mPFS) of 9.0 months....The retrospective analysis evaluated 17 patients with relapsed/refractory multiple myeloma (RRMM) treated in a real-world setting outside of clinical trials."

Real-world evidence • Multiple Myeloma

Positioning of Melflufen in Heavily Pretreated RRMM Patients: Real-World Evidence in a Rapidly Evolving Therapeutic Landscape. (PubMed, Eur J Haematol) - "Collectively, our data confirmed the efficacy previously reported with melflufen-dexamethasone and its manageable safety profile, even in elderly patients likely more fragile and more heavily pretreated than those included in the trials. Overall, melflufen-dexamethasone may represent a treatment option, especially for patients refractory to novel immunotherapies or those who are not ideal candidates to receive such treatments while still preserving access to subsequent T-cell redirecting therapies, thereby addressing a significant unmet need in this hard-to-treat patient population."

HEOR • Journal • Real-world evidence • Fatigue • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Thrombocytopenia

Use of melphalan flufenamide (melflufen) in difficult-to-treat patients with multiple myeloma and renal insufficiency or EMD (DKK 2026) - "Vd (12 mo), bendamustine/prednisolone (5 mo), KRd (4 mo), EloRd (9 mo), DaraRd (2 y), daratumumab mono (4 mo), IsaPomd (5 mo), and doxorubicine/bortezomib (2 mo), were used before melflufen 20 mg was initiated in 08/2023...After 3 prior therapies, DaraVRd (2 mo) – GFR: 12 ml/min, EloPd (3 wk), and talquetamab (4 wk), cycle 1 with melflufen 30 mg was started in 04/2025 (GFR: 64 ml/min)... All clinical cases showed that melphalan flufenamide (melflufen) can be administered in a reduced dose and is a highly effective and well-tolerated therapy even in difficult-to-treat patients with reduced renal function and/or EMD."

Clinical • Hematological Malignancies • Mood Disorders • Multiple Myeloma • Nephrology • Renal Disease

Tumor Targeting with Peptide-Drug Conjugates: Showcasing Key Progress and Hurdles. (PubMed, Drug Des Devel Ther) - "We illustrate PDC concepts through specific instances, such as the brain-penetrant paclitaxel trevatide (ANG1005, paclitaxel-Angiopep-2), the radiotherapeutic lutetium (177Lu)-DOTATATE (Lutathera), and the LyP-1-conjugated doxorubicin-loaded liposomes (LyP-1-doxorubicin conjugate) for triple-negative breast cancer...We also address regulatory hurdles that have limited PDC clinical success; for example, currently, only lutetium (177Lu)-DOTATATE is FDA-approved (others, like melphalan flufenamide (melflufen), have faced setbacks). Finally, we outline future directions, including theranostic PDCs, AI-assisted peptide optimization, dual-stimuli linkers, and integration with nanomaterials, to further enhance targeting and efficacy. This comprehensive review integrates findings from recent literature and provides an in-depth perspective on the design, advantages, limitations, and future prospects of PDCs in cancer therapy."

Journal • Review • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies. (PubMed, Clin Lymphoma Myeloma Leuk) - P2, P3 | "These analyses demonstrate a consistent benefit for melflufen and dexamethasone in patients with relapsed/refractory multiple myeloma who have not received an ASCT or progressed >36 months after receiving an ASCT (ClinicalTrials.gov identifier: NCT03151811)."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study. (PubMed, Haematologica) - P3 | "The most common grade ≥3 treatment-emergent adverse events in the melflufen group versus daratumumab group were neutropenia (50% versus 12%), thrombocytopenia (50% versus 8%), and anemia (32% versus 19%). Melflufen plus daratumumab and dexamethasone demonstrated superior PFS and ORR versus daratumumab in RRMM and a safety profile comparable to previously published melflufen studies."

Journal • P3 data • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • Transplantation

Research shows that Pepaxti is effective in high-risk myeloma (Oncopeptides Press Release) - "The findings come from a collaborative study conducted by researchers in Finland, Germany and Sweden, using patient samples, disease models and clinical data....In laboratory testing of bone marrow samples from 24 myeloma patients, Pepaxti showed strong activity across all genetic subgroups, including those with del(17p) and TP53 mutations....Pepaxti triggered rapid cell death and DNA damage in both normal and TP53-deficient myeloma models, indicating a mode of action that does not rely on functional TP53....A post-hoc analysis of the OCEAN study showed that patients with del(17p) treated with Pepaxti and dexamethasone achieved longer progression-free survival compared to pomalidomide-based treatment."

Clinical data • Preclinical • Multiple Myeloma

Efficacy of melflufen in multiple myeloma with mutated or deleted TP53. (PubMed, Exp Hematol Oncol) - P3 | "Post-hoc analysis of the OCEAN trial melflufen-treated del(17p) patient population also demonstrated favorable progression free survival compared to pomalidomide-treated cohort. Our insights into the molecular mechanisms of melflufen activity in TP53-/- myeloma support its clinical efficacy and application in the del(17p) and TP53-/- patient population.Trial registration NCT03151811, registration 2017-05-09."

Journal • Hematological Malignancies • Metabolic Disorders • Multiple Myeloma • Oncology • TP53

Comprehensive cost analysis of 4th line + therapies for relapsed/refractory multiple myeloma in Germany: Drug, co-medication, and office-based treatment perspective (ASH 2025) - "Whilst there is no official myeloma registry in Germany, treatments we considered were reimbursable combination therapies frequently used in the 4 th line treatment of RRMM in Germany in 2023, containing: carfilzomib, daratumumab, elotuzumab, melflufen, selinexor, talquetamab and teclistamab, and newly approved therapeutic options like elranatamab, along with evidence-based recommendations regarding premedication, comedication, and mandatory prophylaxis of treatment-related adverse events, as outlined in the Summary of Product Characteristics (SmPC) and published literature... Costs for myeloma drugs and combinations show a broad variation, from 88.863€ for Elotuzumab/Revlimid/Dexamethasone (ERd), to 178.850€ for talquetamab treatment. The second lowest in terms of annual costs was melflufen with 106.839€, followed by Elotuzumab/Pomalidomide/Dexamethasone (EPd):119.301€, teclistamab: 124.626€, Selinexor/Dexamethasone (Sd): 129.976€, elranatamab: 146.706€ and..."

Cost-analysis • HEOR • Hematological Malignancies • Multiple Myeloma

Single-arm meta-analysis of melflufen-based regimens in relapsed/refractory multiple myeloma: Efficacy and safety insights from clinical trials (ASH 2025) - "Meflufen showed significant efficacy in RRMM, especially when used as triplet regimen and in double-class refractory disease. Triple therapies were particularly linked with higher overall response and better survival. This supports the use of Meflufen in previously treated RRMM and provides nuanced evidence to guide clinicians to make informed decisions in heavily pretreated RRMM."

Retrospective data • Hematological Malignancies • Multiple Myeloma

Successful melphalan flufenamide (melflufen) therapy in patients with severe renal insufficiency (ASH 2025) - "Before melflufen, the patient received 5 prior therapies all of which were discontinued due to different reasons: VMP (10 mo) – progredient disease (PD), Rd (3 mo) – drug exanthema, Vd (7 mo) - PD, DaraKd (10 mo) – heart insufficiency, and DaraPd (4 mo) which was adjusted to daratumumab monotherapy due to side effects on pomalidomide...In total, 9 different prior therapies were administered and discontinued before the use of melflufen: thalidomide/doxorubicine/dexamethasone (12 mo) with thalidomide as a maintenance therapy (2 y) – PD, Vd (12 mo) – polyneuropathy, bendamustine/prednisolone (5 mo) - PD, KRd (4 mo) – VGPR, discontinuation due to patient's request, EloRd (9 mo) – VGPR, DaraRd (2 y) and daratumumab monotherapy (4 mo) - PD, IsaPomd (5 mo) – PD, and liposomal doxorubicine/bortezomib (2 mo)... Both clinical cases showed that melphalan flufenamide (melflufen) can be administered in a reduced dose of e.g. 20 mg and is a highly effective and well-tolerated..."

Clinical • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Hematological Malignancies • Infectious Disease • Metabolic Disorders • Multiple Myeloma • Musculoskeletal Diseases • Nephrology • Orthopedics • Pulmonary Arterial Hypertension • Renal Disease • Type 2 Diabetes Mellitus • B2M

Unmet Needs in Multiple Myeloma and Potential Solutions: A Systemic Literature Review (ASH 2024) - "Other unmet needs reported were patient and family experience/supportive care (11%), pathophysiology (4%), diagnosis/response assessment (4%), toxicity management/prevention (3%) and poor prognosis (4%).Unmet needs that were reported starting from 2010 [and their proposed solutions] include treatment of high-risk cytogenetic features (4%) [elotuzumab/isatuximab/melflufen/selinexor/anti-BCMA conjugates], treatment of plasma cell leukemia/extramedullary disease (3%) [utilizing MM drugs (daratumumab/boretezemib/melfufen/frontline ASCT etc.)], prevention/management of toxicities (mucositis, neuropathy, nephropathy and GVHD) (1%) [CR4056/amifostine/cannabidiol], treatment/prevention of thromboembolism (1%) [risk assessment model for thromboembolism/studies on anticoagulation], treatment of frail/elderly (1%) [SEA BCMA/melflufen], immune response in MM (<1%) [immunological studies], and measures to assess response to treatment (<1%) [heavy light chain ratio/DW..."

Review • Geriatric Disorders • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Mucositis • Multiple Myeloma • Oncology • Orthopedics • Plasma Cell Leukemia • Renal Disease • Respiratory Diseases

Comparative Efficacy of Ciltacabtagene Autoleucel Versus Elotuzumab, Isatuximab, and Selinexor-Based Regimens in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma with 1-3 Prior Lines of Therapy Using a Matching-Adjusted Indirect Comparison (ASH 2023) - "Other therapies used to treat patients with multiple myeloma who have received at least one other therapy and are lenalidomide-refractory vary by country, but broadly include doublet and triplet regimens based on daratumumab, pomalidomide, bortezomib, and carfilzomib...Melflufen+d, PanVd, VenVd, PCd, IxaKd, D-monotherapy, V-monotherapy, CyVd, and DVCd were not of interest for the US, EU-5, the Netherlands, and Canada...Due to differences in methods for the comparisons versus ide-cel (KarMMa-3) and versus DKd, Kd, DVd, Vd, and Pd, these are reported separately... Cilta-cel demonstrated clinical benefit over EloPd, IsaPd, and SVd for response outcomes and PFS, highlighting its potential as an effective treatment option for patients with RRMM who have received at least one other therapy and are lenalidomide-refractory. These comparisons provide valuable information to contextualize the efficacy of cilta-cel in countries where treatment for these patients may be different..."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Efficacy of the Peptide Drug Conjugates Melflufen and OPDC3 in Venetoclax Resistant Acute Myeloid Leukemia (ASH 2024) - "Background : The combination of BCL2 inhibitor venetoclax with a hypomethylating agent (azacitidine or decitabine) or low dose cytarabine has transformed acute myeloid leukemia (AML) treatment, especially for older patients who are unfit for intensive chemotherapy. For OPDC3, the proportion of the HSC/prog like cells, HSC/MPP cells and neutrophils in the samples showed significant association with the drug response. Conclusion : Based on ex vivo, functional assessment, the peptide drug conjugates melflufen and OPDC3 are highly active in AML, especially in models with primary or acquired resistance to venetoclax and support further investigations of these drugs in venetoclax-resistant AML."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • ANXA5 • CD14 • CD34 • KIT • PTPRC

Long-Term Outcomes from the Phase 3 OCEAN (OP-103) Study: Melflufen and Dexamethasone (Dex) Versus Pomalidomide (Pom) and Dex in Relapsed Refractory Multiple Myeloma (RRMM) (ASH 2023) - P3 | " Pts with RRMM (2-4 prior LoTs including lenalidomide [len] and a proteasome inhibitor) refractory to len and last LoT were randomized 1:1 (stratified by age, no. Long-term results were consistent with those of previous analyses (Schjesvold, et al. Lancet Haematol. 2022; 9:e98-e110)."

P3 data • Anemia • Hematological Malignancies • Infectious Disease • Lymphoma • Multiple Myeloma • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytopenia

Trends in Medicare Spending on Multiple Myeloma Drugs, 2013 to 2021 (ASH 2023) - "Lenalidomide (68%) and pomalidomide (52%) had the largest price increases...Spending on the three myeloma drugs approved via accelerated approval but subsequently withdrawn from the market following confirmatory trials was $85,328,842 (melflufen: $859,764, belantamab: $31,749,711, panobinostat: $52,719,367). Spending data demonstrate prescriber sensitivity to route-of-administration-specific toxicities: almost no intravenous bortezomib was prescribed, and in 2021, >60% of patients on daratumumab received subcutaneous Darzalex Faspro. Second-in-class anti-CD38 antibody isatuximab offered daratumumab little competition (623 beneficiaries received isatuximab vs 20,573 receiving daratumumab)...Our analysis underscores why the Inflation Reduction Act—and its key provisions of inflationary rebates and Medicare price negotiation—are vital to rein in Medicare spending. Generic competition, particularly for lenalidomide and bortezomib, whose patents expired recently, may also..."

Medicare • Reimbursement • US reimbursement • Hematological Malignancies • Multiple Myeloma • Oncology

The Impact of the Peptide Drug Conjugate Melflufen on the Myeloma Tumour Microenvironment (ASH 2023) - "Finally, we observed proliferation of CD34+CD38- progenitor cells, which might be relevant for lymphocyte proliferation and function, and additionally supporting potential modulating effect. Further analyses are being done to validate these findings."

IO biomarker • Tumor microenvironment • Hematological Malignancies • Multiple Myeloma • Oncology • CD34 • CD8

Optimizing the use of melflufen (melphalan flufenamide) in relapsed or refractory multiple myeloma: recommendations for clinical practice. (PubMed, Ann Hematol) - "Melflufen, a first-in-class peptide-drug conjugate, is approved in the European Union and the United Kingdom in combination with dexamethasone for the treatment of adult patients with multiple myeloma (MM) who have received at least three prior lines of therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody, and who have demonstrated disease progression on or after the last therapy. Melflufen is recommended in patients with no prior high-dose melphalan therapy or in those with a long treatment-free interval after such treatment (> 36 months). In high-risk patients, including patients with del(17p) and TP53 gene mutations, melflufen may be considered as a treatment option, especially if patients have not previously been treated with high-dose melphalan."

IO biomarker • Journal • Review • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Transplantation • TP53

Melflufen: PDC, a modern treatment option for multiple myeloma (DGHO 2025) - "Sponsored by Oncopeptides."

Hematological Malignancies • Multiple Myeloma

Exceptional long-term responses from OCEAN and HORIZON trials: melflufen-dexamethasone as an expansion of treatment options for relapsed/refractory multiple myeloma in the era of new immunotherapies? (PubMed, J Cancer Res Clin Oncol) - P2, P3 | "This combination was subsequently withdrawn as it was not associated with improved overall survival (OS) as compared to pomalidomide-dexamethasone (OCEAN clinical trial, NCT03151811). In this paper, we report three cases of patients receiving the combination melflufen-dexamethasone in the aforementioned clinical trials in three hematologic centers across Europe and achieving exceptionally long responses as compared to the overall enrolled populations, with good tolerability. Further, we discuss the potential use of this chemotherapy-based regimen in the era of novel immunotherapies."

Journal • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Real-World Use of Melflufen plus Dexametasone in Relapsed/Refractory Multiple Myeloma: A Retrospective Study from the Valencian Community and the Region of Murcia (Spain) (IMS 2025) - "Introduction: Melphalan fluflenamide (melflufen) in combination with dexamethasone (Melf-dex) has recently been approved in patients with relapsed/refractory multiple myeloma (RRMM) after ≥3 prior lines of therapy. This is the first real-world report on the use of Melf-dex in a cohort of patients previously exposed to anti-BCMA and anti-GPRC5D therapies. Although this population was more heavily pretreated, the efficacy observed was comparable to that reported in clinical trials. These findings suggest that Melf-dex may represent a valuable treatment option in this challenging setting."

Real-world • Real-world evidence • Retrospective data • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Septic Shock • Thrombocytopenia

Real-world Evidence of Melflufen Plus Dexamethasone in Heavily Pretreated Relapsed/refractory Multiple Myeloma Patients: Efficacy and Safety from a Single-center Experience (IMS 2025) - "Of 11 patients receiving subsequent therapies, 7 (64%) were treated with new immunotherapies: belantamab mafodotin (n=2), anti-BCMA BsAbs (n=4), and CAR-T (n=1). Overall, melflufen plus dexamethasone showed encouraging results and manageable safety profile in heavily pretreated RRMM patients. These data support a role for this combination, even in patients refractory to anti-BCMA therapies, without limiting access to future T-cell redirecting therapies, filling a largely unmet clinical need in this patient setting."

Clinical • HEOR • Real-world • Real-world evidence • Anemia • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Septic Shock • Thrombocytopenia

Oncopeptides carries out rights issue of approximately SEK 150 million and provides update regarding the potential partnership in Japan (Oncopeptides Press Release) - "The purpose of the Rights Issue is to finance the ongoing commercialization of Pepaxti in Europe until the Company expects to become cash flow positive by the end of 2026....The Company continues its negotiations with well-established sizeable Japanese pharma companies for the licensing of Pepaxti for the Japanese market..."

Financing • Licensing / partnership • Multiple Myeloma

New real-world data confirms efficacy and safety of Pepaxti, presented at IMS Annual Meeting (Oncopeptides Press Release) - "The Italian study reports an overall response rate (ORR) of 47 percent in a heavily pretreated patient population with relapsed or refractory multiple myeloma....The Spanish study confirms the efficacy of Pepaxti in an even more heavily pretreated patient population where the majority of patients had been exposed to either anti-BCMA or anti-GPRC5D immunotherapy..."

Clinical data • Real-world • Multiple Myeloma

Oncopeptides Partners with SD Pharma to further broaden Pepaxti reach in Spain (Oncopeptides Press Release) - "Oncopeptides AB...announces a partnership with SD Pharma, a leading Spanish pharmaceutical broker specializing in oncology and hematology. This strategic partnership will broaden physician reach of Pepaxti across hospital channels throughout Spain. Under this collaboration, SD Pharma will enhance Oncopeptides’ commercial reach in regions and hospitals beyond its’ core focus areas. The partnership leverages the coordinated efforts of Medical Science Liaisons (MSLs), responsible for clinical education and medical support, and Regional Access Managers (RAMs), who manage treatment access and pharmacy logistics....Activities by SD Pharma are expected to commence in Q3 2025, structured on a success-based model with no upfront or other costs for Oncopeptides."

Licensing / partnership • Multiple Myeloma