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Fostemsavir Serious Adverse Events More Frequent in People Over 50, Men, North Americans
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IAS 2021, 11th IAS Conference on HIV Science, July 18-21, 2021
Mark Mascolini
Serious adverse events proved more frequent in certain groups taking the attachment inhibitor fostemsavir through 96 weeks in the ongoing international BRIGHTE phase 3 trial: people over 50 years old (vs younger), North Americans (vs South Americans and Europeans), men (vs women), and (marginally) blacks/African Americans (vs whites) [1]. Severe safety problems mostly involved infections and infestations and affected people with the lowest pretreatment CD4 counts. Serious adverse events related to study drugs and adverse events leading to stopping treatment were relatively infrequent in this 370-person trial.
Fostemsavir is licensed for people who need it to create a suppressive antiretroviral combination after heavy treatment experience. Prior reports on the phase 3 BRIGHTE trial in heavily treatment-experienced adults with advanced HIV infection and scant treatment options found trends toward increasing HIV control and CD4 rebounds through 96 weeks [2-4]. The report presented at IAS 2021 aimed to integrate safety results compiled so far.
BRIGHTE includes heavily pretreated people whose current antiretroviral combination is failing, as indicated by a viral load above 400 copies/mL. In a nonrandomized trial arm participants had no antiretroviral classes remaining and no licensed fully active drugs available, while in a randomized arm participants had 1 or 2 antiretroviral classes containing 1 or more fully active licensed drugs per class. This randomized group received fostemsavir (600 mg twice daily) plus an optimized background regimen or placebo for 8 days. Eventually, everyone in both arms got open-label twice-daily fostemsavir plus an optimized background regimen. Researchers collected safety data before the SARS-CoV-2 pandemic.
In the combined randomized and nonrandomized groups, 22% were women, 45% were 50 or older, 22% were of African heritage, 25% had a pretreatment viral load above 100,000 copies, and 74% had a pretreatment CD4 count below 200. Study participants in this analysis took fostemsavir for a median of 110.4 weeks (range 1 day to 171.4 weeks).
The most frequent adverse events, in 72% of participants, were infections or infestations. Severe adverse events, including grade 3 or 4 events, serious events, and death, affected a higher proportion of the nonrandomized group and people with low CD4 counts. Overall, 94% of participants had any adverse event, 34% had any grade 3 or 4 event, 37% had any event related to study treatment, 38% had any serious adverse event, 3% had any serious adverse event related to study treatment, 7% had any adverse event leading to stopping study treatment, and 8% died.
Certain adverse event rates differed by study subgroup. Treatment-related adverse events were more frequent in women than men (43% vs 36%) and in whites than blacks (40% vs 29%). Serious adverse events proved more common in men than women (41% vs 28%), in people over 50 years old than in those 35 to 49 or under 35 (46% vs 30% vs 33%), in blacks than whites (43% vs 37%), and in North Americans than in South Americans or Europeans (46% vs 29% vs 29%). Adverse events leading people to stop treatment affected 8% of men, 5% of women, 5% of people younger than 35, 5% of those 35 to 49, 9% of those 50 or older, 10% of whites, 1% of blacks, 9% of North Americans, 9% of Europeans, and 3% of South Americans.
The authors noted that frequency of drug-related adverse events did not differ across baseline CD4 count brackets. They proposed that cumulative safety findings through 96 weeks of BRIGHTE “are consistent with expectation” for this highly pretreated group with high rates of advanced HIV infection and comorbidities.
IAS: LONG-TERM (96-WEEK) SAFETY OF FOSTEMSAVIR (FTR) IN HEAVILY TREATMENT-EXPERIENCED (HTE) ADULTS INFECTED WITH MULTIDRUG-RESISTANT (MDR) HIV-1 (BRIGHTE PHASE 3 STUDY) - (07/22/21)
References
1. Shepherd B, Ramgopal M, Ackerman P, et al. Long-term (96-week) safety of fostemsavir (FTR) in heavily treatment-experienced (HTE) adults infected with multidrug-resistant (MDR) HIV-1 (BRIGHTE Phase 3 study). IAS 2021, 11th IAS Conference on HIV Science, July 18-21, 2021. Abstract PEB153.
2. Kozal M, Aberg J, Pialoux G, et al. Fostemsavir in adults with multidrug-resistant HIV-1 infection. N Engl J Med. 2020;382:1232-1243. doi: 10.1056/NEJMoa1902493.
3. Lataillade M, Lalezari JP, Kozal M, et al. Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: week 96 results of the phase 3 BRIGHTE study. Lancet HIV. 2020;7:e740-e751.
4. Ackerman P, Thompson M, Molina JM, et al. Long-term efficacy and safety of fostemsavir among subgroups of heavily treatment-experienced adults with HIV-1. AIDS. 2021;35:1061-1072.
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