The US Food and Drug Administration (FDA) has approved two new HIV-1 medicines: DELSTRIGO™, a once-daily fixed-dose combination tablet of doravirine (100 mg), lamivudine (3TC, 300 mg) and tenofovir disoproxil fumarate (TDF, 300 mg); and PIFELTRO™ (doravirine, 100 mg), a new non-nucleoside reverse transcriptase inhibitor (NNRTI) to be administered in combination with other antiretroviral medicines,announced Merc Pharmaceuticals.
The drugs have been approved to treat adults with the most common strain of the virus, HIV-1, and target patients who have received no prior antiretroviral treatment, and are administered orally once daily with or without food, Merck said.
Delstrigo combines doravirine, a new non-nucleoside reverse transcriptase inhibitor (NNRTI), with lamivudine and tenofovir disoproxil fumarate, 2 nucleoside analog reverse transcriptase inhibitors (NRTIs). It carries a Boxed Warning regarding post-treatment acute exacerbation of hepatitis B (HBV) infection.
As part of Merck’s 30-year commitment to the care of people with HIV, we are pleased to now bring forward these two new antiretroviral treatment options, DELSTRIGO and PIFELTRO, which we believe offer a compelling clinical profile for clinicians and people living with HIV,” said Dr. George Hanna, vice president and therapeutic area head of infectious diseases, Global Clinical Development, Merck Research Laboratories. “We are thankful to the researchers as well as those living with HIV and their communities for the collaboration that made today’s approval possible.”
DELSTRIGO and PIFELTRO are contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of DELSTRIGO and PIFELTRO. DELSTRIGO is contraindicated in patients with a previous hypersensitivity reaction to 3TC.
The two drugs bagged the FDA approval based on findings from the pivotal, randomized, multicenter, double-blind, active-controlled Phase 3 trials, DRIVE-AHEAD and DRIVE-FORWARD, evaluating the efficacy and safety of DELSTRIGO and PIFELTRO, respectively, in participants infected with HIV-1 with no antiretroviral treatment history.
The DRIVE-AHEAD Clinical Trial
In DRIVE-AHEAD, 728 participants with no antiretroviral treatment history were randomized and received at least one dose of either DELSTRIGO or efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV 600 mg/FTC 200 mg/TDF 300 mg) once daily. DELSTRIGO demonstrated sustained viral suppression through 48 weeks, meeting its primary endpoint of non-inferior efficacy compared to EFV/FTC/TDF (84% in the DELSTRIGO group achieved viral suppression of HIV-1 RNA <50 copies/mL vs. 81% in the EFV/FTC/TDF group; treatment difference
Read AlsoAt Week 48, DELSTRIGO-treated participants showed statistically significant superior lipid profiles as measured by changes from baseline in LDL-cholesterol and non-HDL-cholesterol In addition, a statistically significant lower proportion of DELSTRIGO-treated participants compared to EFV/FTC/TDF-treated participants reported neuropsychiatric adverse events.
The DRIVE-FORWARD Clinical Trial
In DRIVE-FORWARD, 766 participants with no antiretroviral treatment history were randomized and received at least one dose of either PIFELTRO once daily or darunavir 800 mg + ritonavir 100 mg (DRV+r) once daily, each in combination with emtricitabine (FTC)/TDF or abacavir (ABC)/3TC selected by the investigator. PIFELTRO demonstrated sustained viral suppression through 48 weeks, meeting its primary endpoint of non-inferior efficacy compared to DRV+r, each in combination with FTC/TDF or ABC/3TC (84% in the PIFELTRO group achieved viral suppression of HIV-1 RNA <50 copies/mL vs. 80% in the DRV+r group; treatment difference.
At Week 48, PIFELTRO-treated participants showed statistically significant superior lipid profiles as measured by changes from baseline in LDL-cholesterol and non-HDL-cholesterol.
DELSTRIGO and PIFELTRO can be co-administered with a wide range of non-antiretroviral agents, and PIFELTRO can be co-administered with a wide range of antiretroviral agents.
Delstrigo will be available as 100mg/300mg/300mg strength tablets in 30-count bottles. Pifeltro will be available as 100mg strength tablets in 30-count bottles.