Fostroxacitabine bralpamide (fostrox)

  • Mechanism

    Nucleotide DNA polymerase inhibitor (oral)

  • Disease areas

    Hepatocellular carcinoma

    Hepatocellular carcinoma

Fostroxacitabine bralpamide (fostrox) - for the treatment of liver cancers

Fostrox is being developed for patients with primary liver cancer (hepatocellular carcinoma (HCC). HCC is the sixth most common cancer type and the third most common cause of death, worldwide1. In Europe and the USA it is still a rare disease, even if the incidence is increasing2, and fostrox has received orphan medicinal drug designation by EMA and the FDA for the treatment of HCC.

1) Serraino D. et al., Epidemiological Aspects of Hepatocellular Carcinoma. Springer International Publishing, 3–9, 2023

2) Hepatocellular carcinoma, Nature Review 2021



How fostrox complement current therapy options

Fostrox is Medivir's proprietary, liver-targeted drug for the treatment of tumors in the liver. Fostrox is a type of smart chemotherapy and has been developed to achieve a tumor-selective, targeted effect in the liver, while minimizing the effect on normal cells. This mechanism makes it possible to direct a high concentration of fostrox to the liver with reduced risk of side effects in the rest of the body. Based on promising preclinical and clinical data in primary liver cancer (HCC), Medivir has chosen to initially focus fostrox clinical development on this cancer type.

Although existing therapies for advanced HCC can extend the lives of patients, treatment benefits are often insufficient, and death rates remain at a high level. Molecularly targeted drugs have had limited success in HCC because of the heterogenous character of the tumor, with a wide range of mutations, leading to lack of effective actionable targets. The low overall benefit with current treatment regimens, together with the generally poor prognosis for patients with HCC, results in a large unmet medical need. Through its mode of action, fostrox has the potential to be effective independent of type of mutations.

Promising strategies in order to overcome treatment limitations - Interview with Dr Hong Jae Chon

In order to get a specialized clinician’s view on what future developments we might see that could improve the situation for liver cancer patients, we have talked to Dr. Hong Jae Chon about the treatment alternatives that are currently used for liver cancer and where fostrox will fit in the treatment landscape. Dr. Hong Jae Chon is a Professor at Digestive Cancer Center at CHA Bundang Medical Center, CHA University in Korea. He specializes in liver cancer and pancreatic cancer. He is an investigator in the fostrox program and an experienced investigator in numerous national and international clinical trials of new cancer therapies within his specialty indications.

Liver-directed anti-tumor activity

Fostrox is being developed as an orally administrated, liver-targeted and tumor selective drug for the treatment of HCC. The intention is to achieve maximum concentration of the active substance in the liver, while minimizing the levels of the active substance in the rest of the body to reduce the risk of side effects. By sparing the normal liver cells, the tumor selective effect of fostrox is particularly important for patients with HCC, where a majority of patients suffer from liver cirrhosis and poor liver function. Fostrox has the potential to be the first liver cancer-targeted and orally administered drug that can help patients with HCC as well as those with cholangiocarcinoma or liver metastases from other types of cancer.


Clinical development of fostrox in patients with liver cancer

The first-in-human study of fostrox is an open label, multi-center dose escalation/dose expansion study. The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and signs of antitumor effect of fostrox in patients with tumors in the liver as well as identifying the recommended phase 2 dose (RP2D) for fostrox.

The first completed part of the study, phase 1a/1b monotherapy, enrolled patients with advanced hepatocellular carcinoma (HCC), patients with intrahepatic cholangiocarcinoma and patients with liver metastases from solid tumors. Investigated doses were generally well-tolerated and liver biopsies showed selective DNA damage in liver tumor tissue while normal liver tissue was minimally or not affected by the treatment. From the patient biopsies, we also observed DNA damage in hypoxic (oxygen-poor) regions in the tumor, which generally provides difficulties for drugs to be effective. The tumor selective DNA damage effect was observed at low plasma concentrations of fostrox and acceptable exposure to the active metabolite.

The second and ongoing part of the study, phase 1b/2a combination enrolled patients with advanced HCC who have progressed on, or are intolerant of, first or second line standard therapy. It comprises two arms with dose escalation of fostrox in combination with either Lenvima® or Keytruda® and a subsequent dose expansion cohort with recommended phase 2 dose of fostrox in combination with Lenvima. The study is currently conducted at 15 clinics in the UK, Spain and South Korea.

In February 2023, the enrolment of patients into the dose escalation part with fostrox in combination with Lenvima, was successfully completed. The preliminary results were encouraging with a good safety and tolerability profile and no dose-limiting toxicity observed. The recommended dose (RP2D) was determined to 30 mg once daily for 5 days in a 21 day cycles for fostrox in combination with standard dose for Lenvima. In March 2023, the first patient in the dose expansion cohort started treatment with fostrox RP2D in combination with Lenvima.

The dose escalation part for the combination with Keytruda was completed in June 2023, establishing a safe dose for treatment with fostrox in combination with Keytruda. However, considering a treatment landscape where an immune combination is used in first line HCC, a decision was made to focus on the fostrox and Lenvima combination for treatment of HCC in second line. The possibility of combining fostrox with immune therapy is intended to be explored in earlier treatment-lines.

The phase 1b/2a clinical data of fostrox in combination with Lenvima, were first presented in October 2023 where efficacy was evaluated by investigators and local radiologists in 18 of a total of 21 included patients, with at least 12 weeks of follow-up. These data indicate a marked improvement compared to what was shown in second-line HCC in previous studies, with an overall response rate of 22% and a median time to progression of ~5 months. No new, unexpected side effects were reported and the need to reduce the dose of Lenvima, when combined with fostrox, was lower but relatively similar to what is seen with Lenvima used as monotherapy.

Medivir presented updated data from the phase 1b/2a study at the ASCO Gastrointestinal Cancers Symposium, on January 19, 2024 in San Francisco, USA. This analysis included 20 patients with more than 18 weeks of follow-up. The data evaluated by investigators and local radiologists, show further improvement with an Objective Response Rate (ORR) that had increased to 25% (RECIST v1.1) and the median time to progression extended to 5.4 months. Importantly, continued good tolerability with no new unexpected side effects were seen at this time point.

Efficacy data has since continued to improve with >40% of patients still on treatment as of Q4 report on February 16, 2024. This means, among other things, that the median time to progression has improved further to 6.3 months and that the patient who benefited the longest remains on treatment after 18 months with continued tumor response. Results that indicate that the addition of fostrox to Lenvima is tolerable with a maintained good safety profile in this study and that the combination has provided an improved clinical effect when compared to treatments used in this patient population.

Scientific Advisory Counsil

In August 2023 a Scientific Advisory Council with world-leading liver cancer experts was formed to support the company in moving the clinical development of fostrox forward.

The Scientific Advisory Council members are;



Population pharmacokinetic modeling of orally administered fostroxacitabine bralpamide (fostrox, MIV-818) and its metabolite troxacitabine in a phase I/IIa liver cancer study

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)

Combinations of fostrox (MIV-818), a novel nucleotide prodrug, with lenvatinib or sorafenib shows increased efficacy in nonclinical hepatocellular carcinoma (HCC) models in vivo

A triple combination of fostrox (MIV-818) with immune checkpoint and kinase inhibition shows increased anti-tumor efficacy in vivo

Fostrox (MIV-818) in combination with anti-PD-1 shows increased efficacy in nonclinical tumor models in vivoLiver biopsy biomarkers in a phase 1 study of the prodrug MIV-818 demonstrates proof-of-concept for cancer in the liver.

Phase 1 study of the novel prodrug MIV-818 in patients with hepatocellular carcinoma (HCC),intrahepatic cholangiocarcinoma (iCCA) or liver metastases (LM)MIV-818 phase 1b

Abstract published at ESMO 2021

MIV-818 phase I data presented at ASCO GI Cancers Symposium 2021

MIV-818 stimulates an anti-tumorimmune response in vitro and enhances the effects of pembrolizumab

Synergistic and additive anti-tumor effects of MIV-818 in combination with sorafenibin nonclinical hepatocellular carcinoma models

The biomarker potential of Ki67 and pH2AX immunohistochemistry in guiding use of the liver-targeting nucleotide MIV-818 in patients with hepatocellular carcinoma

Liver targeting and anti-tumourefficacy of the nucleotide prodrug MIV-818 in nonclinical models of hepatocellular carcinoma

Liver-targeting with the novel nucleotide prodrug MIV-818 designed for the treatment of liver cancers

Defining exposure-PD and efficacy relationships with the novel liver-targeting nucleotide prodrug MIV-818 for the treatment of liver cancers

Selective targeting of the liver with nucleotide prodrugs for the treatment of liver cancers

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