FDA Grants MIV-818 Orphan Drug Status in HCC

The FDA has granted an orphan drug designation to MIV-818 for the treatment of patients with hepatocellular carcinoma.

The FDA has granted an orphan drug designation to the investigational agent MIV-818 for the treatment of patients with hepatocellular carcinoma (HCC), according to Medivir AB, the manufacturer of the oral nucleotide DNA polymerase inhibitor.1

The designation will facilitate the development and review of MIV-818 in HCC. The treatment previously received a positive opinion from the European Medicines Agency's Committee for Orphan Medicinal Products on orphan medicinal product designation.

“It is very satisfying that MIV-818 has received a positive opinion on orphan medicinal drug designation by EMA and has been granted orphan drug designation by the FDA for the treatment of HCC,” Uli Hacksell, CEO of Medivir, stated in a press release.

In March 2020, Medivir announced that the first patient with advanced liver cancer had been dosed with MIV-818 in the phase 1b component of a phase 1/2 trial (NCT03781934).2 The previously completed proof-of-concept phase Ia part of the trial showed that 5 out of 9 patients who received MIV-818 had stable liver disease. Phase 1b aims to establish safety, tolerability, and further efficacy of the treatment.

The National Cancer Institute describes MIV-818 as a “liver-targeting nucleotide phosphoramidate prodrug of troxacitabine monophosphate (TRX-MP), a dioxolane derivative and L-configuration deoxycytidine analogue, with potential antineoplastic activity.”3 MIV-818 is administered as oral capsules.

Overall, the open-label, nonrandomized phase 1/2 study has a targeted enrollment of 102 patients.4 Phase 2 of the study will comprise 2 cohorts: 1 group of patients with HCC and 1 group of patients with intrahepatic cholangiocarcinoma. The estimated completion data for the trial is December 31, 2021.

The study is enrolling adult patients aged ≥18 years old with ≥1 target lesion in the liver. Patients must have an ECOG performance status of 0 or 1 at baseline and a life expectancy of at least 12 weeks per the investigator’s determination. The following are additional inclusion criteria: baseline ALT and AST ≤5.0 × upper limit of normal; baseline total bilirubin ≤3.0 mg/dL; adequate renal function at baseline with estimated creatinine clearance ≥60 mL/min; baseline platelets ≥75,000/mL; baseline International Normalized Ratio (INR) ≤1.7.

Patients are excluded from enrollment if they have tumor volume exceeding 50% of liver; a history of previous malignancy within the last 5 years except basal cell carcinoma or carcinoma in situ in solid organ; known CNS or brain metastases, unless previously treated and stable for 3 months; a history of solid organ transplant or bone marrow transplant; and/or are receiving immunosuppressive therapy including oral corticosteroids.

Patients on the trial will be evaluated every 6 weeks until disease progression for up to 1 year. The primary efficacy measure will be overall response rate using RECIST v1.1 and mRECIST.


  1. FDA grants MIV-818 Orphan Drug Designation for the treatment of hepatocellular carcinoma. Published May 6, 2020. https://bit.ly/2WrU1r2. Accessed May 6, 2020.
  2. First liver cancer patient dosed in the MIV-818 phase Ib study. Published March 10, 2020. https://bit.ly/3b7b7zB. Accessed May 6, 2020.
  3. Troxacitabine nucleotide prodrug MIV-818. NCI Drug Dictionary. https://bit.ly/2Wc64df. Accessed May 6, 2020.
  4. A Study to Evaluate MIV-818 in Patients With Liver Cancer Manifestations. ClinicalTrials.gov. Last Updated March 19, 2020. https://bit.ly/2SH4nSQ. Accessed May 6, 2020.