Ibalizumab suppressed HIV-1 in multidrug-resistant patients

Seattle – The antibody ibalizumab combined with an optimized background regimen maintained viral suppression out to 24 weeks, in an open-label extension study of patients with multidrug-resistant HIV-1 infections.

The researchers had previously shown that the drug achieved viral suppression after 7 days in many patients.

Ibalizumab works by blocking an epitope on the second extracellular domain of the CD4 receptor, preventing the HIV virus from entering the cell. The 40 patients in the study had failed on at least one drug in three different classes, though they had to have sensitivity to at least one antiretroviral drug, which was used to construct the optimized background regimen (OBR).

“These patients are the most vulnerable and most at risk in terms of needing a new class of drugs. This is the first new class of drug that will go for approval in a decade,” said Brinda Emu, MD, of the deparment of internal medicine at Yale University, New Haven, Conn., who presented the study in a poster session at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.

The average duration of HIV infection among patients was 21 years. Forty-three percent had to take the investigational agent fostemsavir as part of their OBR. After a 7-day monitoring period, patients received a 2,000-mg IV dose of ibalizumab. Seven days later, at day 14, 83% had achieved at least a 0.5 log₁₀ reduction in viral load, compared with 3% during the monitoring period (P less than .0001); 60% achieved at least a 1 log₁₀ reduction, compared with 0% during the monitoring period (P less than .0001).

The OBR was then started at week 14, and patients received an injection of 800 mg ibalizumab every 2 weeks beginning at day 21 and continuing until week 24.

The current research reports the results of the extension study. At week 24, the mean viral load had decreased 1.6 log_10, compared with baseline – 55% of patients had a decrease of at least 1 log₁₀, and 48% had a reduction of at least 2 log₁₀; 43% of patients had undetectable levels of virus, and 50% had fewer than 200 copies/mL.

Nine patients reported a total of 17 serious adverse events, 1 of which led to drug discontinuation. Overall. there were nine discontinuations due to four deaths, three consent withdrawals, and two losses to follow-up.

“In an indication with very resistant virus and limited options, combining ibalizumab with at least one other active agent can provide a way to decrease viral load and increase CD4+ T cells. What I want to know is, What if we started this a little bit earlier as we do with many of our other drugs?” asked Dr. Emu.

She said that some providers had had concerns that adherence may be low with an injectable drug, but the results were reassuring. “I will say anecdotally that I’ve seen the complete opposite. One of the things we noticed is that seeing these patients every 2 weeks to give them their IV infusions has made them more adherent to the rest of their regimen. Perhaps it’s that ability to check in, and the relationship that builds up over time with your providers. Despite it being an infusional agent, or perhaps because of that, adherence has been pretty good.”

The study was funded by TaiMed Biologics. Dr. Emu has served on TaiMed’s advisory board.
 

[email protected]

Seattle – The antibody ibalizumab combined with an optimized background regimen maintained viral suppression out to 24 weeks, in an open-label extension study of patients with multidrug-resistant HIV-1 infections.

The researchers had previously shown that the drug achieved viral suppression after 7 days in many patients.

Ibalizumab works by blocking an epitope on the second extracellular domain of the CD4 receptor, preventing the HIV virus from entering the cell. The 40 patients in the study had failed on at least one drug in three different classes, though they had to have sensitivity to at least one antiretroviral drug, which was used to construct the optimized background regimen (OBR).

“These patients are the most vulnerable and most at risk in terms of needing a new class of drugs. This is the first new class of drug that will go for approval in a decade,” said Brinda Emu, MD, of the deparment of internal medicine at Yale University, New Haven, Conn., who presented the study in a poster session at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.

The average duration of HIV infection among patients was 21 years. Forty-three percent had to take the investigational agent fostemsavir as part of their OBR. After a 7-day monitoring period, patients received a 2,000-mg IV dose of ibalizumab. Seven days later, at day 14, 83% had achieved at least a 0.5 log₁₀ reduction in viral load, compared with 3% during the monitoring period (P less than .0001); 60% achieved at least a 1 log₁₀ reduction, compared with 0% during the monitoring period (P less than .0001).

The OBR was then started at week 14, and patients received an injection of 800 mg ibalizumab every 2 weeks beginning at day 21 and continuing until week 24.

The current research reports the results of the extension study. At week 24, the mean viral load had decreased 1.6 log_10, compared with baseline – 55% of patients had a decrease of at least 1 log₁₀, and 48% had a reduction of at least 2 log₁₀; 43% of patients had undetectable levels of virus, and 50% had fewer than 200 copies/mL.

Nine patients reported a total of 17 serious adverse events, 1 of which led to drug discontinuation. Overall. there were nine discontinuations due to four deaths, three consent withdrawals, and two losses to follow-up.

“In an indication with very resistant virus and limited options, combining ibalizumab with at least one other active agent can provide a way to decrease viral load and increase CD4+ T cells. What I want to know is, What if we started this a little bit earlier as we do with many of our other drugs?” asked Dr. Emu.

She said that some providers had had concerns that adherence may be low with an injectable drug, but the results were reassuring. “I will say anecdotally that I’ve seen the complete opposite. One of the things we noticed is that seeing these patients every 2 weeks to give them their IV infusions has made them more adherent to the rest of their regimen. Perhaps it’s that ability to check in, and the relationship that builds up over time with your providers. Despite it being an infusional agent, or perhaps because of that, adherence has been pretty good.”

The study was funded by TaiMed Biologics. Dr. Emu has served on TaiMed’s advisory board.
 

[email protected]

Seattle – The antibody ibalizumab combined with an optimized background regimen maintained viral suppression out to 24 weeks, in an open-label extension study of patients with multidrug-resistant HIV-1 infections.

The researchers had previously shown that the drug achieved viral suppression after 7 days in many patients.

Ibalizumab works by blocking an epitope on the second extracellular domain of the CD4 receptor, preventing the HIV virus from entering the cell. The 40 patients in the study had failed on at least one drug in three different classes, though they had to have sensitivity to at least one antiretroviral drug, which was used to construct the optimized background regimen (OBR).

“These patients are the most vulnerable and most at risk in terms of needing a new class of drugs. This is the first new class of drug that will go for approval in a decade,” said Brinda Emu, MD, of the deparment of internal medicine at Yale University, New Haven, Conn., who presented the study in a poster session at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.

The average duration of HIV infection among patients was 21 years. Forty-three percent had to take the investigational agent fostemsavir as part of their OBR. After a 7-day monitoring period, patients received a 2,000-mg IV dose of ibalizumab. Seven days later, at day 14, 83% had achieved at least a 0.5 log₁₀ reduction in viral load, compared with 3% during the monitoring period (P less than .0001); 60% achieved at least a 1 log₁₀ reduction, compared with 0% during the monitoring period (P less than .0001).

The OBR was then started at week 14, and patients received an injection of 800 mg ibalizumab every 2 weeks beginning at day 21 and continuing until week 24.

The current research reports the results of the extension study. At week 24, the mean viral load had decreased 1.6 log_10, compared with baseline – 55% of patients had a decrease of at least 1 log₁₀, and 48% had a reduction of at least 2 log₁₀; 43% of patients had undetectable levels of virus, and 50% had fewer than 200 copies/mL.

Nine patients reported a total of 17 serious adverse events, 1 of which led to drug discontinuation. Overall. there were nine discontinuations due to four deaths, three consent withdrawals, and two losses to follow-up.

“In an indication with very resistant virus and limited options, combining ibalizumab with at least one other active agent can provide a way to decrease viral load and increase CD4+ T cells. What I want to know is, What if we started this a little bit earlier as we do with many of our other drugs?” asked Dr. Emu.

She said that some providers had had concerns that adherence may be low with an injectable drug, but the results were reassuring. “I will say anecdotally that I’ve seen the complete opposite. One of the things we noticed is that seeing these patients every 2 weeks to give them their IV infusions has made them more adherent to the rest of their regimen. Perhaps it’s that ability to check in, and the relationship that builds up over time with your providers. Despite it being an infusional agent, or perhaps because of that, adherence has been pretty good.”

The study was funded by TaiMed Biologics. Dr. Emu has served on TaiMed’s advisory board.
 

[email protected]