Standard DoseInvestigational drug at press time. In clinical trials, the investigational dose taken forward for further study was 600 mg, sometimes once daily and sometimes twice daily. Doses were taken after eating. Must be taken in combination with another antiretroviral(s).
Recommended for heavily treatment-experienced patients with history of 3-class antiretroviral resistance in addition to an optimized background regimen of other active antiretroviral drugs. Not studied in treatment-naïve patients at this time. No data in pregnant women or pediatric patients under age 18 years.
Take missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose.
Investigational drug at press time.
AWPNot yet established.
Potential Side Effects and Toxicity
- See package insert when available for more complete information on potential side effects and interactions.
In the Phase 3 BRIGHTE study results out to one year (48 weeks), a third of participants experienced one or more serious adverse event (SAE), mostly infections (of which pneumonia was most common). Three percent of the SAEs were related to fostemsavir. A high rate of SAEs in the study population is not unexpected, given the heavily HIV treatment-experienced background of participants, and likely their advanced disease. In a week 24 BRIGHTE safety report, 91% of participants had experienced at least one adverse event, mostly Grade 1 or 2 (mild to moderate). Grade 2 to 4 adverse events (moderate to serious) occurring in a total 18% of participants included nausea (4%), diarrhea (2%), headache (2%), vomiting (2%), fatigue (1%), and asthenia (muscle weakness) (1%). Remember, most of the participants were also taking at least one other new drug. Seventeen participants (5%) died, due to AIDS-related causes or IRIS (immune reconstitution inflammatory syndrome, in which the body begins to wake up “sleeping” illnesses as the immune system improves). Again, this is not unexpected in patients with advanced disease. Six percent of study participants overall discontinued the study due to an adverse event.
Potential Drug Interactions
New interactions continue to be discovered after drug approval. Dose modification of fostemsavir is not required when co-administering with tenofovir DF, ritonavir-boosted atazanavir, ritonavir-boosted darunavir with or without etravirine, etravirine alone, ritonavir alone, or raltegravir + tenofovir DF. Dose modification is also not required when co-administering with rifabutin (with or without ritonavir). It is not recommended to co-administer with rifampin due to significantly reduced levels of fostemsavir. Based on fostemsavir’s metabolism, a theoretical interaction likely exists with statins (drugs used to treat high cholesterol). This may require a dose reduction or adjustment of certain statins when co-administered with fostemsavir. No dose modification necessary when co-administered with methadone or buprenorphine. Fostemsavir could affect oral contraceptive concentrations, especially those containing ethinyl estradiol. If a booster is not given in the regimen with fostemsavir, it may be co-administered with a combined oral contraceptive containing norethindrone and 30 mcg or less of ethinyl estradiol. Tell your provider or pharmacist about all medications, herbals, and supplements you are taking or thinking of taking, prescribed or not, as there are other drug interactions which are not listed here.
May be FDA approved this year. Fostemsavir is the first HIV drug of its type to get this far in development. It’s a gp120 attachment inhibitor. (That’s under the drug class of HIV entry inhibitors.) Watch a video of its mechanism of action at youtu.be/WnreXE-TVi8. Fostemsavir works on the gp120 protein that lays on the surface of human immune cells. It’s a necessary part of getting the virus to enter the cell. Fostemsavir prevents attachment to the CD4 immune cell by binding to the CD4 receptor binding sites on gp120 on the virus. This causes the virus to accumulate in extracellular space and is subsequently removed by the body’s immune system. Very cool. Fostemsavir is likely to be approved as an oral twice-daily drug, making it unlikely to be used in treatment-naïve individuals. The drug is designed to be used in HIV treatment-experienced people, who typically have fewer options for HIV treatment than those just beginning antiretroviral therapy. An option for treatment-experienced individuals is a good thing. “Even in the era of modern HAART [highly active antiretroviral therapy], antiretroviral (ARV) failure and resistance is still a problem worldwide,” wrote HIV specialist Dr. Pedro Cahn and colleagues in Current Opinion in HIV and AIDS published last July. Dr. Cahn worked on fostemsavir research. See more data online.
Dr. David Hardy says:
Fostemsavir is a prodrug that is metabolized to the active compound temsavir, an attachment inhibitor that binds to glycoprotein 120 (gp120) on the envelope of HIV’s surface. It works by locking HIV gp120 in a conformational state that inhibits the necessary binding between the virus and the CD4+ protein on human T cells, and prevents viral attachment and entry into these cells. Because of its unique mechanism of action, there is no known cross-resistance with other classes of antiretrovirals which may help PLWH whose viruses have become resistant to most other medications. While the BRIGHTE study data has been submitted to the FDA for review, fostemsavir’s approval has been delayed due to manufacturing limitations. It is expected that fostemsavir will be approved and available in 2019. It is given as a tablet twice daily along with other antiretrovirals. The BRIGHTE study (NCT02362503) is a two-cohort (randomized and open-label), Phase 3 clinical trial evaluating the safety and efficacy of fostemsavir in 371 heavily treatment-experienced PLWH. All had documented resistance, intolerability, and/or contraindication to all antiretrovirals in at least four of the six available ART classes. PLWH in the randomized cohort had to have one, but no more than two, fully active antiretroviral classes remaining at baseline, but were unable to construct an effective regimen from their remaining antiretrovirals. These PLWH were randomized 3:1 to add blinded fostemsavir or blinded placebo (n=272) to their current failing regimen for eight days of functional monotherapy. Patients without any remaining fully active approved antiretrovirals (n=99) were assigned to the open-label cohort and received fostemsavir plus other optimized antiretrovirals. The primary endpoint of the study was mean change in viral load between Day 1 and Day 8 for the randomized cohort. After the 8-day blinded period, all patients in the randomized cohort received open-label fostemsavir plus an optimized ART regimen. By Day 8, those PLWH who received fostemsavir saw their viral loads drop by 0.8 log10, or about 6.5-fold, compared with a 0.2 log10 drop among those who received placebo, thus confirming fostemsavir’s anti-HIV activity in highly treatment-experienced PLWH. After 48 weeks, 62% of PLWH in the randomized group had undetectable viral loads (less than 40 copies/mL) and 86% had viral loads below 400 copies/mL. Among PLWH in the initial open-label group, 48% had viral loads less than 40 copies/mL and 55% had viral loads less than 400 copies/mL. PLWH in the randomized group experienced an average rise in CD4+ T cells of 139/mm3, while those in the initial open-label group gained an average of 64 CD4+ T cells/mm3.
Activist Moisés Agosto-Rosario says:
Fostemsavir is developed to be used in PLWH with multi-drug resistance. Fostemsavir is a prodrug. When the drug is taken, it metabolizes to the active compound, temsavir, which inhibits the binding of HIV to CD4+ T cells through blocking the HIV gp120 receptor. Since this is a highly conserved protein between HIV strains, fostemsavir has a high genetic barrier to resistance, and its novel method of action provides an alternative option for patients with highly resistant viral HIV strains.