The FDA has approved Rukobia (fostemsavir) for the treatment of human immunodeficiency virus 1 (HIV-1) infection. The medication is indicated in combination with other antiretroviral medications in heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1 infection who are failing their antiretroviral regimen because of intolerance, resistance, or safety considerations.¹ HTE adults account for about 6% of adults with HIV-1 who are using treatment.²

PHARMACOLOGY AND PHARMACOKINETICS

Rukobia is a glycoprotein 120-directed attachment inhibitor. It is a prodrug that is hydrolyzed to its active moiety, temsavir. Temsavir binds directly to the glycoprotein 120 subunit of the HIV-1 envelope and selectively inhibits the interaction between the virus and cellular CD4 receptors. In addition, temsavir can inhibit glycoprotein 120-dependent post-attachment steps that are required for viral entry into host cells.

Temsavir reaches maximum plasma concentrations 2 hours after oral administration and displays an elimination half-life of 11 hours. Age, ethnicity, race, and sex do not affect its pharmacokinetics.¹

DOSAGE AND ADMINISTRATION

The dose of Rukobia is 600 mg twice daily. The medication is supplied as an extended-release tablet which can be taken with or without food.¹

CLINICAL TRIALS

Rukobia was evaluated in a double-blind, international, partially randomized, placebo-controlled trial of 371 HTE adults with multiclass HIV-1 resistance and a viral load of at least 400 copies/mL. Participants were enrolled in either a nonrandomized or randomized cohort. The randomized cohort consisted of 272 participants who were using at least 1 and no more than 2 fully active and approved antiretroviral medications. In addition to their current regimen, participants in the randomized cohort received either blinded Rukobia 600 mg twice daily or a placebo. After 8 days, the randomized cohort received open-label Rukobia 600 mg twice daily plus an investigator-selected optimized background therapy (OBT). The nonrandomized cohort, consisting of 99 adults who were not using any fully active and approved antiretroviral medications, received open-label Rukobia 600 mg twice daily in addition to OBT. The primary efficacy end point was the adjusted mean decline in HIV-1 RNA from day 1 to day 8 in the randomized cohort, which demonstrated the superiority of Rukobia compared with the placebo. The randomized cohort achieved HIV-1 RNA of less than 40 copies/mL in 53% of participants at week 24 and in 60% of participants at week 96, with mean changes in CD4+ T-cell count increasing from baseline.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Treatment with Rukobia is contraindicated in patients with a hypersensitivity to any of its components. It is also contraindicated during coadministration with strong cytochrome P450 3A inducers, as this combination may cause significant decreases in plasma concentrations, leading to a loss of virologic response.

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapies. Rukobia should be used cautiously in patients with a history of corrected QT interval prolongation or relevant pre-existing cardiac disease. Caution is advised when Rukobia is used concomitantly with medications that carry a known risk of torsade de pointes. Older patients may be more susceptible to drug-induced QT interval prolongation. A greater proportion of patients with hepatitis B and/or hepatitis C coinfection experienced elevated hepatic transaminases compared with patients with HIV monoinfection. No dose adjustment is required for patients with hepatic or renal impairment. Concurrent use of Rukobia and oral contraceptives increases ethinyl estradiol concentrations, and patients using this combination should not use more than 30 mcg of ethinyl estradiol daily. Breastfeeding during treatment with Rukobia is not recommended because it presents the potential for HIV-1 transmission to an HIV-negative infant, the development of viral resistance to an HIV-positive infant, and adverse reactions in infants.

The most common adverse reaction in patients taking Rukobia is nausea.¹

Monica Holmberg, PharmD, BCPS, earned her PharmD at the University of Connecticut in Storrs and completed an ambulatory care residency at the Phoenix VA Health Care System in Arizona. Her practice has also included pediatrics and inpatient mental health. She lives in Phoenix.

REFERENCES

• Rukobia. Prescribing information. ViiV Healthcare; 2020. Accessed July 29, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212950s000lbl.pdf
• Viiv Healthcare announces US FDA approval for Rukobia (fostemsavir), a first-in-class treatment for HIV in adults with few treatment options available. Press release. Viiv Healthcare. July 2, 2020. Accessed July 29, 2020. https://viivhealthcare.com/en-gb/media/press-releases/2020/july/viiv-healthcare-announces-us-fda-approval-for-rukobia/