An estimated 1.1 million people in the United States are living with the human immunodeficiency virus (HIV) (CDC, 2018b). The predominant and most common type of HIV virus is referred to as HIV-1. HIV-1 accounts for around 95% of all infections worldwide. HIV attacks the body’s immune system, specifically the CD4 cells (T cells), which help the immune system fight off infections. Untreated, HIV reduces the number of CD4 cells (T cells) in the body, making persons more prone to get other infections or infection-related cancers. When a CD4 count is lower than 200 cell/mm3, and/or opportunistic infections or cancers take advantage of an already weakened immune system, a person may receive a diagnosis of AIDS, acquired immunodeficiency syndrome, which is the last stage of HIV infection. There is no cure, but there are many medicines, known as antiretroviral therapy (ART), that fight HIV infection and lower the risk of developing AIDS (AIDSinfo, 2018; Bartlett, 2018; CDC, 2018a).

An HIV viral load (HIV RNA) test measures the number of HIV particles (also known as copies) in a milliliter (mL) of blood. The viral load reflects how much HIV is in the blood. A viral load threshold of <1000 copies/mL defines treatment success according to the 2016 WHO consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. A high viral load may indicate that an HIV regimen is not effective. The goal of HIV treatment is to reduce viral load to very low or undetectable levels (HIV.gov, 2017; WHO, 2016).

There are many HIV medicines available to treat HIV-1. The HIV medicines (ART) are grouped into seven drug classes according to how they fight HIV. These classes include nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors, CCR5 antagonists, integrase strand transfer inhibitors (INSTIs), and post-attachment inhibitors. A person’s initial HIV regimen usually includes three HIV medicines from at least two different HIV drug classes. When HIV multiplies in the body, the virus sometimes mutates and makes variations of itself, which can lead to drug-resistant strains of HIV (AIDSinfo, 2018).

Ibalizumab-uiyk (Trogarzo) (TaiMed Biologics, Inc), a post-attachment inhibitor, is a recombinant humanized monoclonal antibody that blocks HIV-1 from infecting CD4+ T cells by binding to domain 2 of CD4 and interfering with post-attachment steps required for the entry of HIV-1 virus particles into host cells, thereby preventing the viral transmission that occurs via cell-cell fusion. The binding specificity does not impact CD4 function that cause immunosuppression. Trogarzo is the first CD4-directed post-attachment HIV-1 inhibitor and the first humanized monoclonal antibody for the treatment of refractory HIV-1 (FDA, 2018; Iacob et al, 2017; Markham, 2018; TaiMed, 2018).

On March 6, 2018, the U.S. Food and Drug Administration (FDA) announced the approval of Trogarzo (ibalizumab-uiyk) for use in combination with antiretroviral regimen in heavily treatment-experienced adults (18 years of age and older) with multidrug resistant (MDR) HIV-1 infection failing their current antiretroviral regimen (FDA, 2018; Markham, 2018; TaiMed, 2018). The FDA granted Fast Track, Priority Review, Breakthrough Therapy designation, as well as Orphan Drug designation.

FDA approval was based on the safety and efficacy evaluation of Trogarzo in a phase 3, single arm, 24-week, multicenter study which evaluated 40 heavily treatment-experienced subjects with multidrug resistant HIV-1 who continued to have high levels of HIV-RNA virus in their blood despite being on antiretroviral drugs. Subjects were required to have a life expectancy greater than 6 months, a viral load greater than 1,000 copies/mL and documented resistance to at least one antiretroviral medication from each of three classes of antiretroviral medications (NRTI, NNRTI, and PI) as measured by resistance testing. Subject must have been treated with antiretroviral for at least 6 months and be failing or have recently failed (i.e., in the last 8 weeks) therapy. Subjects received a single 2,000 mg IV loading dose of Trogarzo followed 7 days later by the initiation of an optimized background regimen (OBR) including at least one agent to which the subject’s virus was susceptible. Two weeks after the Trogarzo loading dose, 800 mg of Trogarzo was administered IV. The IV administration of Torgarzo 800 mg was continued every 2 weeks through Week 25. The primary efficacy endpoint was the proportion of subjects who achieved a decrease in viral load from Day 7 to Day 13 as compared to the proportion who achieved a decrease from Day 0 to Day 6. The outcomes reflected a majority of subjects who experienced a significant decrease in their HIV-RNA levels one week after Trogarzo was added to their failing antiretroviral regimens. At Week 25, 43 percent achieved HIV-RNA suppression (ClinicalTrials.gov, NCT02475629; TaiMed, 2018).

Although the clinical trial focused on a small patient population with limited treatment options, the study demonstrated the benefit of Trogarzo in achieving reduction of HIV RNA. The seriousness of the disease, the need to individualize other drugs in the treatment regimen, and safety data from other trials were considered in evaluating the Trogarzo development program (FDA, 2018).

As of March 2018, a total of 292 patients with HIV-1 infection have been exposed to Trogarzo IV infusion. The most common adverse reactions (incidence greater than or equal to 5 percent) to Trogarzo were diarrhea, dizziness, nausea and rash. Severe side effects included rash and changes in the immune system (immune reconstitution syndrome) (FDA, 2018, TaiMed, 2018).

Aetna considers ibalizumab-uiyk (Trogarzo) injectable medically necessary for use in combination with antiretroviral regimen in heavily treatment-experienced adults (18 years of age and older) with multidrug resistant (MDR) HIV-1 infection who are failing current antiretroviral regimen meeting all of the following criteria:

Aetna considers ibalizumab-uiyk (Trogarzo) experimental and investigational for all other indications because of insufficient evidence in peer-reviewed published literature.

* The following are the three antiretroviral medication classes noted in the medical necessity criteria as per the clinical study eligibility criteria that FDA approval was based upon:

** HAART = Highly active antiretroviral therapy is a form of drug treatment for human immunodeficiency virus (HIV) infection consisting of a course of at least three antiretroviral drugs, a potent drug "cocktail", used to suppress the growth of HIV, the retrovirus responsible for acquired immunodeficiency syndrome (AIDS).

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Dosing Recommendations

Trogarzo is available in a single-dose, 2 mL vial containing 150 mg/mL of ibalizumab-uiyk. Each vial delivers approximately 1.33 mL containing 200 mg of ibalizumab-uiyk.

Trogarzo is administered intravenously (IV) by a trained medical professional, after diluting the appropriate number of vials in 250 mL of 0.9 % sodium chloride injection, USP. After dilution, Trogarzo is administered as a single loading dose of 2,000 mg (10 vials; 13.3 mL) followed by a maintenance dose of 800 mg (4 vials; 5.32 mL) every 2 weeks.

Dose modifications of Trogarzo are not required when administered with any other antiretroviral or any other treatments.

Source: Prescribing Information. Trogarzo (ibalizumab-uiyk) injection, for intravenous use. 2018.