Regulatory press release

Medivir announces new clinical trial collaboration and supply agreement with Eisai to evaluate fostrox in combination with lenvatinib in advanced liver cancer

Agreement to support expansion of fostroxacitabine bralpamide (fostrox) program with a randomised phase 2b study evaluating fostrox in combination with lenvatinib vs lenvatinib alone in second-line advanced liver cancer (HCC).

Phase 1b/2a data has demonstrated that the combination of fostrox + lenvatinib has shown to have a manageable safety profile and encouraging anti-tumor activity in second-line population, including a median time to progression (TTP) of 10.9 months [1].

Medivir’s fostrox is the first oral, liver-targeted treatment in development for advanced liver cancer. Its unique mechanism delivers the cell-killing compound to tumor cells locally in the liver while minimizing harm to healthy cells.

Stockholm, Sweden, 2024 — Medivir AB (Nasdaq Stockholm: MVIR), a pharmaceutical company focused on developing innovative treatments for cancer in areas of high unmet medical need, today 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. Lenvatinib will be dosed as per regulatory approved dosing in advanced liver cancer.

"This clinical trial collaboration and supply agreement with Eisai allows us to build on the encouraging phase 1b/2a data by expanding our fostrox program with a randomized phase 2b study in combination with lenvatinib," said Jens Lindberg, CEO of Medivir. “In our ongoing phase 1b/2a study, fostrox + lenvatinib has shown to have a manageable safety profile and encouraging anti-tumor activity for second-line liver cancer patients. Fostrox + lenvatinib has the potential to become the first, approved treatment option after first-line treatment with immunotherapy combination, a population with an estimated market value in excess of $2.5bn by 2030.”

“There continues to be an unmet need for patients suffering from Hepatocellular carcinoma (HCC), a major cause of cancer-related deaths,” said Dr. Takashi Owa, Chief Scientific Officer, Senior Vice President, Eisai Co., Ltd. “The results from the ongoing phase 1b/2a study with the combination of fostrox and lenvatinib in second-line advanced liver cancer are encouraging. Our collaboration with Medivir for the upcoming randomized phase 2b study aims to advance a new therapeutic option for patients with HCC.”

Data from the ongoing phase 1b/2a study of fostrox with lenvatinib has been recently presented at ESMO GI in Munich in June and ESMO in Barcelona in September. At these presentations, the combination demonstrated a manageable safety profile and encouraging anti-tumor activity, with a median time to progression of 10.9 months, an Objective Response Rate of 24% and a Disease Control Rate of 81%. Fostrox’ liver targeted and tumor cell specific effect, sparing healthy cells, was confirmed as evidenced by preserved liver function over the duration of treatment. This, together with overall tolerability, contributed to patients staying on treatment much longer than anticipated and experiencing an extended duration of benefit.

About fostrox
Fostrox is a liver-targeted inhibitor of DNA replication that delivers the cell-killing compound selectively to the tumor while minimizing the harmful effect on normal cells. This is achieved by coupling an active chemotherapy (troxacitabine) with a prodrug tail. This design enables fostrox to be administered orally and travel directly to the liver where the active substance is released locally in the liver. With this unique mechanism, fostrox has the potential to become the first liver-targeted, orally administered drug that can help patients with various types of liver cancer. A phase 1b monotherapy study with fostrox has been completed and a phase 1b/2a combination study in HCC is ongoing where it has shown encouraging anti-cancer efficacy with a good safety and tolerability profile (ref Chon et al., ESMO 2024, Poster 986).

About lenvatinib
Lenvatinib, discovered by Eisai and co-developed and co-commercialized under a collaboration agreement with Merck & Co., Inc., Rahway, NJ, USA, is an orally available multiple receptor kinase inhibitor that inhibits vascular endothelial growth factor receptors (VEGFRs),VEGFR1, VEGR2, VEGFR3 and fibroblast growth factor receptors (FGFRs), FGFR1, FGFR2, FGFR3, FGFR4, and other receptor tyrosine kinases, PDGFR-alpha, KIT, RET. Lenvatinib has various approvals worldwide, including in thyroid cancer, hepatocellular carcinoma, thymic cancer, and renal cell carcinoma (in combination with everolimus or KEYTRUDA® (pembrolizumab), Merck & Co., Inc., Rahway, NJ, USA’s anti-PD-1 therapy). Lenvatinib is also approved for endometrial cancer in combination with pembrolizumab.

About primary liver cancer
Primary liver cancer is the third leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is the most common cancer that arises in the liver and it is the fastest growing cancer in the USA. Although existing therapies for advanced HCC can extend the lives of patients, treatment benefits are insufficient and death rates remain high. There are approximately 660,000 patients diagnosed with primary liver cancer per year globally and current five-year survival is less than 20 percent [2], [3]. HCC is a heterogeneous disease with diverse etiologies, and lacks defining mutations observed in many other cancers. This has contributed to the lack of success of molecularly targeted agents in HCC. The limited overall benefit, taken together with the poor overall prognosis for patients with intermediate and advanced HCC, results in a large unmet medical need.

About Medivir
Medivir develops innovative drugs with a focus on cancer where the unmet medical needs are high. The drug candidates are directed toward indication areas where available therapies are limited or missing and there are great opportunities to offer significant improvements to patients. Medivir is focusing on the development of fostroxacitabine bralpamide (fostrox), a drug candidate designed to selectively treat cancer cells in the liver and to minimize side effects. Collaborations and partnerships are important parts of Medivir’s business model, and the drug development is conducted either by Medivir or in partnership. Medivir’s share (ticker: MVIR) is listed on Nasdaq Stockholm’s Small Cap list. www.medivir.com.

About Eisai Co., Ltd.
Eisai’s Corporate Concept is “to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides.” Under this “human health care (hhc)” Concept, we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to deliver innovative products to address unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology and Global Health. For more information, please visit www.eisai.com, X, LinkedIn and Facebook.

1) Chon et al., ESMO 2024, Poster 986
2) Rumgay et al., European Journal of Cancer 2022 vol.161, 108-118.
3) Yang, J.D., Hainaut, P., Gores, G.J. et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 16, 589–604 (2019).

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