fostroxacitabine bralpamide (MIV-818) / Medivir - LARVOL DELTA

Medivir aims to become the first approved treatment option for second-line liver cancer (BioStock) - "Following positive clinical results, Medivir intends to continue the development of fostrox, the company's targeted candidate for patients with advanced liver cancer at the highest rate. On December 2, a rights issue of SEK 151 million will be completed, the aim of which is to finance a randomized, comparative phase II study with fostrox....The next step is a randomized phase II study in collaboration with the Korean Cancer Study Group, led by principal investigator Dr. Hong-Jae Chon at CHA Bundang Hospital in Seoul. The study compares fostrox + lenvatinib with lenvatinib as monotherapy in two arms with approximately 40 patients per arm."

Financing • New P2 trial • Hepatocellular Cancer • Liver Cancer

Medivir receives Notice of Allowance for fostrox plus lenvatinib combination patent from Japan Patent Office [Google translation] (Medivir Press Release) - "Medivir AB...announces today that the Japan Patent Office (JPO) has issued a Notice of Allowance for the company's patent application covering patent protection for the combination of fostroxacitabine bralpamide (fostrox) and lenvatinib (Lenvima) for the treatment of hepatocellular carcinoma (HCC) and liver metastases from other types of cancer....A Notice of Allowance indicates that the JPO intends to approve the application after completing some formal steps. The patent provides protection and market exclusivity until April 2041."

Patent • Hepatocellular Cancer

MIV-818-101: A Study to Evaluate MIV-818 in Patients With Liver Cancer Manifestations (clinicaltrials.gov) - P1/2 | N=53 | Completed | Sponsor: Medivir | Active, not recruiting ➔ Completed

Trial completion • Biliary Cancer • Cholangiocarcinoma • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Medivir receives European patent for fostrox plus lenvatinib in treatment of hepatocellular carcinoma (HCC) and cancer metastases in the liver (Medivir Press Release) - "Medivir AB...announces today that the European patent authority has granted the company's patent application covering claims for the combination of fostroxacitabine bralpamide (fostrox) with lenvatinib (Lenvima) for the treatment of hepatocellular carcinoma and cancer metastases to the liver. The patent provides protection and market exclusivity until April 2041....In light of our positive, final data from the phase 1b/2a study presented at the EASL Liver Cancer Summit last month, and the ongoing activities to initiate a phase 2b study in 2nd line HCC, it is key to protect the unique fostrox plus lenvatinib combination in HCC..."

Patent • Hepatocellular Cancer

Medivir presents positive final phase 1b/2a fostrox + Lenvima data in advanced liver cancer at EASL Liver Cancer Summit (Medivir Press Release) - P1/2a | N=53 | NCT03781934 | Sponsor: Medivir | "Today’s EASL update, poster number P02-13...confirmed encouraging efficacy with a median overall survival of 13.7 months in second- or third line advanced liver cancer patients. All patients in the study had tumor progression on previous treatment but subsequently showed tumor reduction in >75% of the patients treated with fostrox + Lenvima. The tumor reduction correlated with reduction in AFP levels from baseline to 6 weeks that were seen in 79% of patients. This is encouraging as AFP is a liver cancer biomarker where high AFP levels negatively impact outcome. The result from this study showed that tumor reduction was seen independent of AFP levels (≥400 ng/mL<). The treatment with fostrox + Lenvima continued to be safe and tolerable with no unexpected new adverse events."

P1/2 data • Hepatocellular Cancer

Final safety and efficacy results from the phase 1b/2a study of fostrox plus lenvatinib in second/third line patients with advanced hepatocellular carcinoma who progressed on immunotherapy (LCS 2025) - P1/2 | "Median age 62 y (range: 42-82); 76% male; 29% ECOG PS 1; 86% prior atezolizumab/bevacizumab, 24% primary refractory on prior treatment, 70% prior TACE/RFA, 67% extra hepatic disease and 45% had AFP ≥400 ng/mL. Fostrox in combination with LEN was tolerable and safe with promising efficacy (TTP = 10.9 months) in a high unmet need HCC population. A randomized phase 2b of fostrox + LEN versus LEN alone is planned to further explore the potential benefit of this combination."

Clinical • Metastases • P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Medivir announces new clinical trial collaboration and supply agreement with Eisai to evaluate fostrox in combination with lenvatinib in advanced liver cancer (Medivir Press Release) - "Medivir AB...announced a clinical trial collaboration and supply agreement with Eisai Co., Ltd. (Eisai) to evaluate fostrox in combination with lenvatinib mesylate (product name: Lenvima, 'lenvatinib') in a randomized, phase 2b study in second-line advanced liver cancer patients (hepatocellular carcinoma/HCC). Under the terms of the agreement, Medivir and Eisai forms a Joint Development Committee, responsible for the planning and implementation of the study. In addition, Eisai will provide a multiple receptor tyrosine kinase inhibitor lenvatinib, a key component of the study, to be used in all study arms. Medivir retains full rights to fostrox. The study will incorporate two dosing levels of fostrox in a dose optimization run-in before selecting recommended dose."

Commercial • Hepatocellular Cancer

Medivir to present final safety and efficacy data for fostrox + Lenvima in advanced liver cancer at EASL Liver Cancer Summit (Medivir Press Release) - "Medivir AB...today announced that final safety and efficacy data from the phase 1b/2a study of fostrox (fostroxacitabine bralpamide) in combination with Lenvima (lenvatinib) for the treatment of advanced hepatocellular carcinoma (HCC) has been accepted for presentation at the European Association for the Study of the Liver (EASL) Liver Cancer Summit in Paris, February 20-22, 2025...End of treatment safety and efficacy data will be presented at the conference in Paris.er Cancer Summit in Paris, February 20-22, 2025."

P1/2 data • Hepatocellular Cancer

Medivir obtains IND approval for fostrox - the first oral, liver-targeted treatment for advanced liver cancer (Medivir Press Release) - "Medivir AB...announced the approval of the US Investigational New Drug application (IND) for evaluating fostrox + Lenvima vs Lenvima alone in a phase 2b study in 2nd line advanced HCC....The randomized phase 2b study will evaluate the combination of fostrox + Lenvima vs Lenvima alone in second-line advanced HCC patients who have previously been treated with an immunotherapy combination. The primary endpoint is Objective Response Rate with secondary endpoints including duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety and Quality of Life....Medivir plans to recruit patients in at least 8 countries across USA, Europe and Asia, aiming for study read-out in 2027."

IND • New P2b trial • Hepatocellular Cancer

MIV-818-101: A Study to Evaluate MIV-818 in Patients with Liver Cancer Manifestations (clinicaltrials.gov) - P1/2 | N=53 | Active, not recruiting | Sponsor: Medivir | Trial completion date: Feb 2024 ➔ Jun 2025 | Trial primary completion date: Feb 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Biliary Cancer • Cholangiocarcinoma • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Medivir announces finalisation of the phase 1b/2a study with fostrox + Lenvima in advanced liver cancer, remaining patients transferred to compassionate use (Medivir Press Release) - "Medivir AB...announced that the phase 1b/2a study of fostroxacitabine bralpamide (fostrox) + Lenvima in 2nd or 3rd line advanced liver cancer (HCC), closed on November 26th. The 3 remaining patients in the study have been transferred to compassionate use, allowing continued benefit from the treatment....Patients have stayed on treatment longer than anticipated and the 3 remaining patients have each been on treatment for at least 15 months....With the study now closed, the company plans to present end-of-treatment data at an upcoming scientific congress."

P1/2 data • Trial status • Hepatocellular Cancer

Medivir to present mature clinical data for fostrox + Lenvima at ESMO Conference and to host a webcast on September 16 (PRNewswire) - "Medivir AB...has previously announced that detailed and mature data from the phase 1b/2a study of fostrox (fostroxacitabine) in combination with Lenvima (lenvatinib) for the treatment of advanced hepatocellular carcinoma (HCC) will be presented at the European Society for Medical Oncology (ESMO) Congress in Barcelona, September 16, 2024."

P1/2 data

A Phase 1a/1b Study of Fostroxacitabine Bralpamide (Fostrox) Monotherapy in Hepatocellular Carcinoma and Solid Tumor Liver Metastases. (PubMed, J Hepatocell Carcinoma) - "The phase 1a/1b monotherapy study of fostrox, in patients with liver tumors, showed a tumor selective effect in the liver and that 40 mg QD for 5 days in 21-day cycles is safe and tolerable. Safety and preliminary efficacy in patients with advanced HCC supports clinical development of fostrox in combination with other modes of action in HCC."

Clinical • Journal • Monotherapy • P1 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Hepatocellular Cancer • Hepatology • Liver Cancer • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia

Fostrox (fostroxacitabine bralpamide) plus lenvatinib in patients with locally advanced unresectable or metastatic hepatocellular carcinoma (HCC) progressed on immunotherapy combinations: Results from a multi-center phase Ib/IIa study (ESMO 2024) - P1/2 | "Fostrox plus lenvatinib may be a future option for patients progressed on an immunotherapy combination, if the encouraging safety and efficacy data in phase 1b/2a will be confirmed in a later randomized study."

Clinical • Metastases • P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Medivir's fostrox + Lenvima confirm promise of improved outcomes in advanced liver cancer, detailed and mature data presented at ESMO (PRNewswire) - P1b/2a | N=53 | NCT03781934 | Sponsor: Medivir | "Medivir AB...presented positive, mature data from its ongoing phase 1b / 2a study of fostroxacitabine bralpamide (fostrox) + Lenvima in advanced liver cancer (hepatocellular carcinoma/HCC) at the ESMO (European Society of Medical Oncology) Congress....Mature results from Medivir's phase 1b / 2a open label trial of fostrox + Lenvima confirm improved outcomes in second-line advanced liver cancer with a median time to progression (TTP) of 10.9 months1 (4.1 - 18.1). The results showed an objective response (ORR) of 24%, and a median duration of response of 7.0 months. Detailed safety update reinforces the ability to combine fostrox and Lenvima long-term, only 1 patient discontinuing fostrox due to adverse events."

P1/2 data • Hepatocellular Cancer

Medivir to present updated clinical data for fostrox + Lenvima in HCC at ESMO Conference in September (PRNewswire) - "Medivir AB...is pleased to announce that updated data from the phase 1b/2a study of fostrox (fostroxacitabine) in combination with Lenvima (lenvatinib) for the treatment of advanced hepatocellular carcinoma (HCC) has been accepted for presentation at the European Society for Medical Oncology (ESMO) Congress in Barcelona, September 13-17, 2024...Updated clinical data from the ongoing phase 1b/2a study with fostrox in combination with Lenvima will be presented."

P1/2 data • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Fostrox + Lenvima holds promise of greatly improved outcomes for advanced liver cancer patients, reveals new data from Medivir at ESMO GI (PRNewswire) - P1b/2a | N=53 | NCT03781934 | Sponsor: Medivir | "Medivir AB...presented positive new data from its ongoing phase Ib / IIa study of fostroxacitabine bralpamide (fostrox) + Lenvima in advanced hepatocellular carcinoma (HCC) at the ESMO GI (European Society of Medical Oncology, Gastrointestinal Cancers) Cancers Congress....Fostrox + Lenvima achieved a 24% overall response rate (ORR) and estimated median time to progression (TTP) of 10.8 months1 (4.1 - NE) - with one patient still on treatment after 22 months. Results come despite very poor prognosis for most second-line HCC patients today, with just 5 - 10% responding to current standard of care treatment, and a typical TTP of only 3 - 4 months."

P1/2 data • Hepatocellular Cancer

Liver pharmacodynamics in an open-label phase Ib/IIa study of fostroxacitabine bralpamide (fostrox, MIV-818) in combination with lenvatinib in 2L/3L hepatocellular carcinoma (ESMO-GI 2024) - P1/2 | "Median age was 62 years (range 42-82), viral etiology in 76%, extra hepatic metastases in 67%, prior progression on atezolizumab/bevacizumab in 86%. Liver pharmacodynamics together with liver function test supports emerging clinical data on safety and efficacy with fostrox in combination with lenvatinib in 2L/3L advanced HCC."

Clinical • Combination therapy • P1/2 data • PK/PD data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • SLC2A1

Medivir to present at Redeye Growth Day (PRNewswire) - "Medivir AB...announces that the company will participate at Redeye Growth Day, today May 30, 2024. CEO Jens Lindberg will present updated data from the ongoing phase 1b/2a clinical study with fostroxacitabine bralpamide (fostrox) and the development plans moving forward at 09.40 CET."

P1 data • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Medivir to present data for the combination of fostrox + Lenvima in HCC at ESMO GI (PRNewswire) - "Medivir AB...announced today that an abstract for the combination of fostroxacitabine bralpamide (fostrox) + Lenvima in hepatocellular carcinoma (HCC) has been accepted for presentation at the European Society for Medical Oncology (ESMO) Gastrointestinal (GI) Cancers Congress in June 26-29, 2024 in Munich....The presentation will include pharmacodynamic data from patients in the ongoing phase Ib/IIa clinical study with fostrox + Lenvima combination, evaluating the impact on normal liver function and DNA damage in tumor cells vs healthy cells. The presentation will also include an update on efficacy endpoints as the study has continued to mature and patients have been able to stay on treatment."

P1/2 data • Hepatocellular Cancer

Medivir provides update from supportive Type C meeting with the FDA; preparations for enhanced phase 2b in HCC with fostrox + Lenvima continue (PRNewswire) - "Medivir AB...announced today an update from a Type C meeting with the FDA, regarding the company's plans for a global phase 2b study and opening of an IND for fostroxacitabine bralpamide (fostrox) in the US. The key outcome of the Type C meeting was that Medivir's preparations for the randomized phase 2b study, comparing fostrox + Lenvima with Lenvima alone, continues with two key adjustments to the study design. Firstly, as Medivir plans to use the improved capsule formulation of fostrox in the upcoming phase 2b study, an initial dose run-in as the first part of the study will be added....Secondly, Objective Response Rate (ORR) is a validated surrogate endpoint for Overall Survival....The next step is to finalize the study design and study protocol before submitting an IND in the US to enable study start in the beginning of 2025."

FDA event • IND • Hepatocellular Cancer

Medivir hopes for accelerated approval if Phase IIb HCC trial is successful (Clinical Trials Arena) - "Medivir said it is targeting accelerated approval of its lead candidate fostroxacitabine bralpamide (fostrox) once it completes a Phase IIb trial in hepatocellular carcinoma (HCC). CEO Jens Lindberg told the Clinical Trials Arena that the Swedish company is looking to initiate the Phase IIb trial by the end of the year once getting approval from the US Food and Drug Administration (FDA). The trial will investigate Medivir’s lead candidate fostrox as a second-line combination therapy with Eisai’s Lenvima (lenvatinib)....If the trial is successful, Lindberg said the company will use the data to apply to the FDA for accelerated approval."

New P2b trial • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Medivir presents data that strengthens the fostrox/Lenvima combination in primary liver cancer at EASL Liver Cancer Summit (PRNewswire) - P1/2a | N=53 | NCT03781934 | Sponsor: Medivir | "Medivir AB...announced today that clinical pharmacokinetic (PK) data on dose linearity and systemic exposure from the first study with fostroxacitabine bralpamide...The presentation includes pharmacokinetic results from 42 patients in the phase I/IIa clinical study with fostrox monotherapy and the fostrox + Lenvima combination in advanced liver cancer...The results show dose linearity and that the systemic exposure, at the recommended phase 2 dose for fostrox, aligns with the encouraging safety and tolerability profile experienced in the ongoing phase 1b/2a study with fostrox in combination with Lenvima in second line treatment of advanced hepatocellular carcinoma (HCC). In addition, the study shows that the exposure of fostrox is not impacted by administration of Lenvima, providing additional support for this combination."

P1/2 data • Hepatocellular Cancer

Population pharmacokinetic modeling of orally administered fostroxacitabine bralpamide (fostrox, MIV-818) and its metabolite troxacitabine in a phase I/IIa liver cancer study (LCS 2024) - P1/2 | "Fostrox is in clinical development in combination with lenvatinib in patients with hepatocellular carcinoma (HCC). The PK models described the fostrox and troxacitabine data well with dose linear increase in exposure and linear elimination of both moieties"

Clinical • P1/2 data • PK/PD data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

First safety and efficacy data from phase Ib/IIa study of fostroxacitabine bralpamide (fostrox, MIV-818) in combination with lenvatinib in patients with hepatocellular carcinoma (HCC). (ASCO-GI 2024) - P1/2 | "Fostrox in combination with lenvatinib, in pts with HCC who progressed on previous systemic treatment, had an acceptable safety and tolerability profile with promising interim efficacy results from the completely enrolled phase Ib/IIa study. Clinical trial information: NCT03781934."

Clinical • Combination therapy • P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor