Trogarzo

The most common adverse reactions observed in clinical studies were diarrhea (8%), dizziness (8%), nausea (5%), and rash (5%). Select lab abnormalities noted to occur in at least 5% of studied patients were increased bilirubin by greater than 2.6 times ULN (upper limit of normal), 5%; increased creatinine (greater than 1.8 times ULN or 1.5x baseline), 10%; increased lipase (greater than 3 times ULN), 5%; decreased leukocytes, 5%; and decreased neutrophils, 5%. Most (90%) of the adverse reactions reported were mild or moderate in severity. No formal studies were conducted to examine the effects of either renal or hepatic impairment on the pharmacokinetics of Trogarzo. Renal impairment is not anticipated to affect the pharmacokinetics of Trogarzo. Based on animal data using higher doses of medication than would be used in humans, the FDA updated the drug label last year to include the potential for transient immunosuppression in infants exposed to the drug inside the womb. See Section 8.1 (Pregnancy) in the prescribing information for more details.

Based on Trogarzo’s mechanism of action and pharmacokinetic profile, drug-drug interactions are not expected. No formal drug interaction studies have been conducted with Trogarzo.

Essentially, this drug is for heavily treatment-experienced people with multidrug resistance, along with an optimized background regimen (OBR). Go to bit.ly/Trogarzo-mechanism-of-action to watch a YouTube video of its mechanism of action. A key point is that people must still take other HIV medications that have some activity—there has to be at least one HIV drug to which their virus is sensitive included in their OBR. DHHS HIV treatment guidelines list Trogarzo this way: “People with ongoing detectable viremia [detectable viral load] who lack sufficient treatment options to construct a fully suppressive regimen [get to undetectable viral load] may be candidates for the recently approved [in 2018] CD4 post-attachment inhibitor ibalizumab.” Trogarzo is a newer option, but it does come with some rules. Non-adherence won’t be an option—people won’t be able to just show up whenever they want or be late to appointments when going to an infusion center. People must be on time. It is expensive because the cost of the drug is in addition to other expenses such as the time at the infusion center and cost for qualified individuals to administer and handle the medication, although there may be an option for people to receive their infusion at home. Infusions can also be done at clinics and at IV centers.

Although given once every two weeks, because it must be used with other HIV medications, antiviral treatment will still be required to be taken daily. Other long-acting HIV drugs are on the way, however, and may be studied in combination with Trogarzo as well. Trogarzo is also the first HIV orphan drug—one that is produced for a relatively small population of people, fewer than 200,000. It was produced for people with multidrug-resistant HIV, estimated to be fewer than 40,000 in the U.S.; the company estimates there are fewer than 25,000. These are heavily treatment-experienced people who have multidrug resistance, and have, therefore, limited treatment options. Trogarzo has been shown to work against highly drug-resistant virus, when combined with an OBR. Data presented at ID Week 2020 showed evidence for long-term safety and efficacy as well as tolerability in people receiving Trogarzo for almost a decade. Trogarzo has also demonstrated CD4 improvements in clinical studies.

As a biologic, IBA is the first HIV medication produced in cells rather than from chemicals. This does not make Trogarzo better, just different. Trogarzo works differently from any other HIV drug currently on the market. It binds to a domain (location) of the CD4 receptor (in this case, domain 2), blocking viral entry into the CD4 cell. Most HIV drugs target parts of HIV, which are variable and thus susceptible to resistance. Trogarzo works against both CCR5 and CXCR4 virus, and may be synergistic with some other classes of antiretrovirals. Resistance test results revealed no evidence of cross-resistance between Trogarzo and any of the approved classes of HIV drugs. Trogarzo is neither metabolized in the liver nor eliminated by the kidneys. Monoclonal antibodies such as ibalizumab are transported across the placenta as pregnancy progresses; therefore, the developing fetus has the potential to be exposed to Trogarzo. Pregnant individuals can voluntarily enroll in the Antiretroviral Pregnancy Registry through their provider; go to apregistry.com.

Thera Patient Support can assist with private or government insurance coverage, including AIDS Drug Assistance Program (ADAP), and will also assist in applying any eligible co‑pay assistance. Commercially insured people may be eligible for co-pay assistance and may pay as little as $0. Call (833) 23-THERA (833-238-4372), or go to therapatientsupport.com.

Dr. Melanie Thompson:

Ibalizumab is an entry inhibitor that has activity against multidrug-resistant HIV. It requires intravenous infusions every 2 weeks, and at a wholesale acquisition cost of $9,896 per month, is the most expensive antiretroviral drug ever approved, and administration costs are not included. Nonetheless, the egregious pricing is accompanied by a patient assistance program that protects people—if not the healthcare system—from much of the financial burden. Still, the drug can be a lifesaver for people with multidrug-resistant virus who cannot otherwise construct a viable regimen. It has no known drug-drug interactions.

Activist Michael Broder:

Trogarzo (ibalizumab) is the first drug in a new class called a CD4-directed post-attachment inhibitor. Trogarzo blocks the virus from entering CD4 cells. Trogarzo is for use only in highly treatment-experienced people, meaning those who have already been on treatment for some time and have virus that is resistant to multiple HIV drugs. People using Trogarzo have virtually no other treatment options. More convenient oral or injectable HIV drugs are in development to treat multidrug-resistant virus in highly treatment-experienced people; but until those drugs are fully evaluated and approved, Trogarzo remains an important tool in the antiretroviral toolbox.