Melanie Thompson1, Jacob P Lalezari2, Richard Kaplan3, Yvett Pinedo4, Otto A Sussmann Pena5, Pedro Cahn6, David A Stock7, Samit R Joshi7, George J Hanna8, Max Lataillade7. 1. AIDS Research Consortium of Atlanta, Atlanta, GA, USA. 2. Quest Clinical Research, San Francisco, CA, USA. 3. Desmond Tutu HIV Foundation, Cape Town, South Africa. 4. Asociacion Civil Via Libre, Lima, Peru. 5. Asistencia Cientifica de Alta Complejidad SAS, Bogotá, Columbia. 6. Fundacion Huesped, Buenos Aires, Argentina. 7. Bristol-Myers Squibb, Wallingford, CT, USA. 8. Bristol-Myers Squibb, Princeton, NJ, USA.
Abstract
BACKGROUND:Fostemsavir is a prodrug of temsavir, an attachment inhibitor that binds directly to HIV-1 gp120, blocking initial viral attachment and entry into host CD4+ T-cells. Efficacy, safety and dose-response data of fostemsavir in treatment-experienced, HIV-1-infected subjects, through week 48, are reported. METHODS: AI438011 is an ongoing Phase IIb, randomized, active-controlled trial (NCT01384734). Subjects were randomized 1:1:1:1:1 into five arms: fostemsavir (400 mg twice daily, 800 mg twice daily, 600 mg once daily or 1,200 mg once daily) and a reference arm (ritonavir-boosted atazanavir [ATV/r] 300/100 mg once daily), each with a backbone of raltegravir 400 mg twice daily plus tenofovir disoproxil fumarate 300 mg once daily. RESULTS: In total, 251 subjects were treated. Through week 48, the proportion of fostemsavir subjects with HIV-1 RNA <50 copies/ml was 61-82% and 77-95% (modified intent-to-treat [mITT] and observed analysis, respectively); 71% and 88% for ATV/r subjects (mITT and observed). Observed virological response rates were 74-100% versus 96% (fostemsavir versus ATV/r) in subjects with baseline viral load <100,000 copies/ml and 60-91% versus 71% when baseline viral load was ≥100,000 copies/ml. Across fostemsavir arms, median CD4+ T-cell count increases from baseline were 145-186 cells/µl and 142 cells/µl for the ATV/r arm. Fostemsavir doses were generally well tolerated and no fostemsavir-related adverse events led to discontinuation. CONCLUSIONS: Through week 48, fostemsavir continued to be well tolerated and showed similar efficacy to ATV/r. These results support the ongoing Phase III trial in heavily treatment-experienced adults with limited therapeutic options (≤2 classes of active antiretrovirals remaining). ClinicalTrials.gov identifier: NCT01384734.
RCT Entities:
BACKGROUND:Fostemsavir is a prodrug of temsavir, an attachment inhibitor that binds directly to HIV-1gp120, blocking initial viral attachment and entry into host CD4+ T-cells. Efficacy, safety and dose-response data of fostemsavir in treatment-experienced, HIV-1-infected subjects, through week 48, are reported. METHODS: AI438011 is an ongoing Phase IIb, randomized, active-controlled trial (NCT01384734). Subjects were randomized 1:1:1:1:1 into five arms: fostemsavir (400 mg twice daily, 800 mg twice daily, 600 mg once daily or 1,200 mg once daily) and a reference arm (ritonavir-boosted atazanavir [ATV/r] 300/100 mg once daily), each with a backbone of raltegravir 400 mg twice daily plus tenofovir disoproxil fumarate 300 mg once daily. RESULTS: In total, 251 subjects were treated. Through week 48, the proportion of fostemsavir subjects with HIV-1 RNA <50 copies/ml was 61-82% and 77-95% (modified intent-to-treat [mITT] and observed analysis, respectively); 71% and 88% for ATV/r subjects (mITT and observed). Observed virological response rates were 74-100% versus 96% (fostemsavir versus ATV/r) in subjects with baseline viral load <100,000 copies/ml and 60-91% versus 71% when baseline viral load was ≥100,000 copies/ml. Across fostemsavir arms, median CD4+ T-cell count increases from baseline were 145-186 cells/µl and 142 cells/µl for the ATV/r arm. Fostemsavir doses were generally well tolerated and no fostemsavir-related adverse events led to discontinuation. CONCLUSIONS: Through week 48, fostemsavir continued to be well tolerated and showed similar efficacy to ATV/r. These results support the ongoing Phase III trial in heavily treatment-experienced adults with limited therapeutic options (≤2 classes of active antiretrovirals remaining). ClinicalTrials.gov identifier: NCT01384734.
Authors: Margaret Gartland; Pedro Cahn; Edwin DeJesus; Ricardo Sobhie Diaz; Robert Grossberg; Michael Kozal; Princy Kumar; Jean-Michel Molina; Fernando Mendo Urbina; Marcia Wang; Fangfang Du; Shiven Chabria; Andrew Clark; Louise Garside; Mark Krystal; Frank Mannino; Amy Pierce; Peter Ackerman; Max Lataillade Journal: Antimicrob Agents Chemother Date: 2022-05-03 Impact factor: 5.938
Authors: Max Lataillade; Nannan Zhou; Samit R Joshi; Sangil Lee; David A Stock; George J Hanna; Mark Krystal Journal: J Acquir Immune Defic Syndr Date: 2018-03-01 Impact factor: 3.731