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

Peptide-Drug Conjugates: A New Hope for Cancer. (PubMed, J Pept Sci) - "Only Lutathera remains FDA-approved after Pepaxto's withdrawal, though Pepaxto retains EMA and MHRA approval-highlighting regulatory and technical complexities. Most PDCs target overexpressed receptors (e.g., somatostatin and GnRH), though novel designs like CBX-12 employ alternative strategies...Promising candidates in late-stage trials are highlighted, emphasising their potential to address unmet needs in oncology. By refining targeting precision and payload delivery, next-generation PDCs may expand treatment options for resistant cancers, bridging the gap between biologics and small-molecule therapies."

Journal • Review • Oncology

Oncopeptides announces net sales for Q2 2025 (Oncopeptides Press Release) - "Oncopeptides releases this information ahead of the interim report for the second quarter 2025 as net sales are determined by the company to be higher than both the company´s projections and assumed market expectations....'The strong start to 2025 is a testament to our team’s operational execution and a growing demand for Pepaxti'....Oncopeptides expects net sales for the second quarter to amount to SEK 19.2 million (SEK 8.2 million for Q2 2024). Oncopeptides expects net sales for the six months period to amount to SEK 32.5 million (SEK 13.2 million for the first six months of 2024). The key reason for the sales increase is stronger-than-expected organic sales growth in Germany, Oncopeptides largest market, combined with faster-than-expected market access in Spain and Italy."

Sales • Multiple Myeloma

Oncopeptides’ drug Pepaxti included in European Guidelines for the treatment of multiple myeloma (Oncopeptides Press Release) - "Oncopeptides AB...announces that its drug Pepaxti has been included in new clinical practice guidelines from EHA-EMN for patients with relapsed, refractory multiple myeloma....The guidelines are based on a thorough evaluation of clinical evidence by leading experts and aim to support doctors in selecting appropriate therapies for their patients. For patients who have received multiple prior lines of therapy and are triple-class refractory/exposed (TCR/TCE) - meaning their disease no longer responds to three major classes of myeloma drugs - Pepaxti is recommended based on Level 1 evidence, the strongest possible, and has a Grade B recommendation....Furthermore, Pepaxti has also been listed as a treatment option for patients with even more advanced disease, TCR/TCE patients relapsing after immunotherapy with either CAR-T cells or ADC and whose disease no longer responds to four drug classes."

Clinical guideline • Multiple Myeloma

Industry promotion of oncology drugs with accelerated approval that failed confirmatory trials. (ASCO 2025) - "Pepaxto was excluded from our analysis as it had no reported payments on OpenPayments...Following announcement of negative postapproval confirmatory study results, average monthly payments received by all physicians increased for Marqibo (vinCRIStine sulfate) from $138 in the year preceding announcement to $164 during the period between announcement of negative results and market withdrawal, but decreased for Farydak (panobinostat) ($12,317 to $4,916), Blenrep (belantamab mafodotin) ($152,417 to $119,394), and Ukoniq (umbralisib) ($23,139 to $14,130). Lartruvo (olaratumab) and Aliqopa (copanlisib) had almost no payments after announcement of negative confirmatory study results. Industry payments for oncology drugs with accelerated approvals mostly decreased after announcement of negative confirmatory trial results; however, there was evidence of continued promotion for certain drugs until a request for voluntary withdrawal was made by FDA. This suggests that regulatory..."

Oncology

Melflufen data insights for TCR RRMM: Safety, Efficacy and QoL (COMy 2025) - "Sponsored by Oncopeptides"

Clinical • Multiple Myeloma

Oncopeptides launches new real-world evidence study of Pepaxti in Spain, first patient enrolled (Oncopeptides Press Release) - "Oncopeptides AB...announces that the first patient has been enrolled in its new real-world evidence study, evaluating the use of Pepaxti in routine clinical settings across Spain. The non-interventional study OP-115, named LAGOON, will include approximately 50 adult patients at approximately 20 participating sites. Its objective is to collect real-world clinical data on the effectiveness and safety of Pepaxti in patients with relapsed, refractory multiple myeloma (RRMM), reflecting the approved indication....The results of the LAGOON study will support Oncopeptides’ efforts to provide relevant real-world data to healthcare providers, payers, and regulators across Europe."

Real-world • Trial status • Multiple Myeloma

New Real-World Data support effectiveness and tolerability of Pepaxti in heavily pretreated Multiple Myeloma patients (Oncopeptides Press Release) - "Oncopeptides AB (publ)...announces the publication of new real-world data that further support the effectiveness and tolerability of melflufen, branded in Europe as Pepaxti, in patients with relapsed, refractory multiple myeloma (RRMM). The data were presented in an abstract from the University of Catania, Italy. It highlights treatment outcomes in a single-center real-world setting. The retrospective analysis included eight triple-class refractory RRMM patients who had received a median of 3.5 prior lines of therapy. Notably, several patients presented with high-risk features, including extramedullary disease. Despite this, treatment with Pepaxti in combination with dexamethasone showed an overall response rate (ORR) of 37.5%, with partial responses seen even among patients with advanced disease manifestations."

Real-world • Retrospective data • Multiple Myeloma

Melflufen for Elderly Patients With Relapsed Myeloma (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Fondazione EMN Italy Onlus | N=30 ➔ 0 | Trial completion date: Aug 2027 ➔ Mar 2025 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Feb 2027 ➔ Mar 2025

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Hematological Malignancies • Multiple Myeloma • Oncology

Oncopeptides receives first order of Pepaxti in Italy (Oncopeptides Press Release) - "Oncopeptides AB (publ)...announces that it has received the first order of its flagship drug Pepaxti (melflufen) from an Italian hospital. Following the positive reimbursement decision and publication in the Gazzetta Ufficiale, Pepaxti has now entered the Italian healthcare system. This allows hospitals to, in certain cases, order the product even before full regional access has been finalized.Italy has a strong foundation of clinical experience with Pepaxti, with 79 patients across 10 hospitals participating in its clinical trials and over 80 patients treated in the Early Access Program (EAP) before formal reimbursement....Italy has a strong foundation of clinical experience with Pepaxti, with 79 patients across 10 hospitals participating in its clinical trials and over 80 patients treated in the Early Access Program (EAP) before formal reimbursement."

Reimbursement • Multiple Myeloma

Strong real-world efficacy and safety data with Pepaxti published in the European Journal of Haematology (Oncopeptides Press Release) - "The retrospective study analyzed 12 patients with RRMM treated with melflufen plus dexamethasone at the Dana-Farber Cancer Institute. The cohort had a median of 5.5 prior lines of therapy, with a significant proportion exhibiting high-risk disease characteristics. Key findings include: 55% ORR, with 27% achieving complete response (CR); 21.3-week median duration of response; Manageable safety profile, with primarily hematologic adverse events; No new safety signals compared to clinical trial data."

Retrospective data • Multiple Myeloma

Outcomes of Melflufen Treatment in Patients With Relapsed/Refractory Multiple Myeloma. (PubMed, Eur J Haematol) - "Consistent with clinical trial data, melflufen had an expected safety profile with manageable toxicity and clinically meaningful efficacy in patients with RRMM treated in the real-world setting."

Journal • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Transplantation

Oncopeptides’ Pepaxti formally approved for full reimbursement in Italy (Oncopeptides Press Release) - "Oncopeptides AB (publ)...announces that the positive reimbursement decision for its drug Pepaxti (melflufen) has been published in the Italian Official Journal ('IOJ', It.: Gazetta Ufficiale). This marks the final regulatory step for the drug’s upcoming commercialization in Italy, confirming Oncopeptides’ expectation of first sales during H1, 2025. With the IOJ publication, Oncopeptides can now initiate the regional access process to bring Pepaxti to patients. The company’s goal is to make the treatment available to eligible Italian patients with relapsed and refractory multiple myeloma over the coming months."

Reimbursement • Multiple Myeloma

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 • Cardiovascular • Geriatric Disorders • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Mucositis • Multiple Myeloma • Novel Coronavirus Disease • Oncology • Orthopedics • Pain • Renal Disease • Respiratory Diseases

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 Disorders • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • ANXA5 • CD14 • CD34 • KIT • PTPRC

Autopsy of a Drug Withdrawal - The Case of Melphalan Flufenamide. (PubMed, N Engl J Med) - No abstract available

Journal

Next-Generation Novel Therapies in Multiple Myeloma (ICBMT 2024) - "A wealth of therapeutic options have been approved for the treatment of newly diagnosed (ND) and relapsed/refractory (RR) multiple myeloma (MM) over the past two decades, with proteasome inhibitors (bortezomib, carfilzomib, ixazomib), immunomodulatory drugs (IMiDs; thalidomide, lenalidomide, pomalidomide), and monoclonal antibodies (mAbs; including the CD38 mAbs daratumumab and isatuximab, as well as the SLAMF7-targeting mAb elotuzumab) currently forming the backbone of treatment approaches in each setting. Additional targeted therapies have further enhanced the armamentarium, including, previously, the histone deacetylase inhibitor panobinostat, and, more recently, the nuclear export inhibitor selinexor 1 and the peptide–drug conjugate (PDC) melflufen. 2,3 Furthermore, novel immune-based treatment options such as the antibody–drug conjugate (ADC) belantamab mafodotin, the BCMA-targeting CAR T-cell therapies idecabta-gene vicleucel (ide-cel) and ciltacabtagene autoleucel..."

Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation • CRBN • IRF4 • SLAMF7

Oncopeptides obtains reimbursement for Pepaxti in Italy (Oncopeptides Press Release) - "Oncopeptides AB...announces that it has come to an agreement with the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA) on the pricing and reimbursement of melflufen, branded in Europe as Pepaxti. The decision paves the way for the drug to be commercialized in Italy during H1, 2025. The agreement with AIFA’s and its Scientific Pricing and Reimbursement Committee (CSE) on market access for Pepaxti at a price that reflects the innovation of Pepaxti and is in line with the financial projections of the company paves the way for Oncopeptides to move forward with the regional access process."

Reimbursement • Multiple Myeloma

Melflufen for Elderly Patients With Relapsed Myeloma (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Fondazione EMN Italy Onlus

New P2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Efficacy of melflufen in patients with relapsed/refractory multiple myeloma and molecular TP53 lesions (DGHO 2024) - "Our data and analysis of the molecular mechanisms of melflufen activity in mutant TP53 MM support the observed clinical efficacy and application in the del(17p) and mutant TP53 patient population."

Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • BCL2 • BCL2L1 • CCNG2 • CDKN1A • SDC1 • TP53 • XRCC1

HARBOUR (OP-113): Non-interventional study of melphalanflufenamide (melflufen) in combination with dexamethasone in patients with relapsed and/or refractory multiple myeloma according to approved indication (DGHO 2024) - "Secondary endpoints include duration of response (DOR), clinical benefit rate (CBR), time to next therapy (TTNT), time to progression (TTP), progression-free survival (PFS) and overall survival (OS), incidence and severity of adverse events, as well as quality of life (EORTC QLQ-C30). The study is ongoing and open for enrollment."

Clinical • Combination therapy • IO biomarker • Observational data • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology

Comparative Efficacy of Cilta-Cel vs Approved Comparator Treatments for Patients With Relapsed/Refractory Multiple Myeloma With 1–3 Prior Lines of Therapy: A Network Meta-Analysis (IMW 2024) - "Introduction: In the phase 3 CARTITUDE-4 trial, ciltacabtagene autoleucel (cilta-cel) prolonged progression-free survival (PFS) vs standard of care (SOC) (HR [weighted], 0.26; P< 0.0001; HR [unweighted], 0.40; P< 0.0001) in patients with lenalidomide (len)-refractory multiple myeloma (MM) and 1–3 prior lines of therapy (LOT), including a proteasome inhibitor and an immunomodulatory drug...The comparator arm in CARTITUDE-4 is SOC treatment with physician's choice of daratumumab, pomalidomide, dexamethasone (DPd) or pomalidomide, bortezomib, dexamethasone (PVd)...This network was centralized around pomalidomide in combination with dexamethasone (Pd) and included the CARTITUDE-4 (cilta-cel), APOLLO (DPd + Pd), ELOQUENT-3 (elotuzumab, pomalidomide, dexamethasone [EloPd]), ICARIA-MM (isatuximab, pomalidomide, dexamethasone [IsaPd]), and OCEAN (melflufen, dexamethasone [Md]) trials... These comparisons provide valuable information to contextualize the efficacy of..."

Retrospective data • Hematological Malignancies • Multiple Myeloma • Oncology

Oncopeptides signs license agreement with SCBIO for Pepaxti in South Korea (Oncopeptides Press Release) - "Oncopeptides AB...announces it has signed an exclusive license and supply agreement with SCBIO Inc., a Korean pharmaceutical company for the commercialization of Oncopeptides’ flagship drug Pepaxti in South Korea....The agreement with SCBIO marks the company´s first licensing agreement, where SCBIO will support Oncopeptides through multiple steps in the value chain, from regulatory approval to commercial sales. Oncopeptides continues to explore similar agreements for other markets including China and Japan."

Licensing / partnership • Multiple Myeloma

The emerging role of melflufen and peptide-conjugates in multiple myeloma. (PubMed, Curr Opin Oncol) - "There have been an interest in developing and utilizing peptide-drug conjugates such as melflufen for treatment of patients with multiple myeloma, especially in the relapsed setting given historical results with alkylating agents, the use of which has been limited by dose-related toxicities in a disease that remains largely incurable. Single agent melflufen initially showed promising results especially in specific subgroups of heavily pretreated patients before the decision to suspend all clinical trials evaluating this agent after results from the OCEAN phase 3 trial. Subsequent reported analyses especially for melflufen-based combinations appear promising and suggest a potential use of peptide-drug conjugates provided optimal patient selection, as well as identification of the best companion agent."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Oncopeptides expands on WODA partnership with addition of Africa and Eurasia to provide Pepaxti to Patients (GlobeNewswire) - "Oncopeptides AB...and Veld Pharmaceuticals GmbH ('Veld') and Slavpharma GmbH ('Slavpharma') today announced a collaboration to commercialize Oncopeptides’ flagship drug Pepaxti (melphalan flufenamide) in Africa and Eurasia. Under the terms of this exclusive agreement, Veld and Slavpharma will distribute Pepaxti to patients in their respective regions for the treatment of patients with multiple myeloma. The parties have agreed on a revenue split on all Pepaxti sales in the region, with Veld and Slavpharma carrying all costs through their existing structure in the region."

Commercial • Hematological Malignancies • Multiple Myeloma • Oncology

Studies towards Cu-mediated flourine-18 labeling of organoboronates in the presence of amino substituents (ACS-Fall 2024) - "We have found that the radio chemical yield could be increased in the presence of amine containing ligands. The effects of these ligands were demonstrated for successful labeling of melflufen analogs, which are promising drug compounds for treatment of multiple myeloma."

Hematological Malignancies • Multiple Myeloma • Oncology