Merck Submits sNDA to FDA for Pifeltro and Delstrigo in Virologically Suppressed HIV-1 Patients Switching Therapy
Jan 25, 2019 17:14
CST Updated
15:40
Merck Group
Pharmaceutical R&D Developer
FDA
U.S. Food and Drug Administration
January 25, 2019/Bio ValleyBIOON/---Merck & Co. recently announced that the U.S. Food and Drug Administration (FDA) has accepted the supplemental New Drug Applications (sNDAs) for two HIV drugs, Pifeltro and Delstrigo. These sNDAs seek approval for Pifeltro (in combination with other antiretrovirals) and Delstrigo for use in HIV-1-infected patients who are switching from a stable antiretroviral regimen and have achieved virologic suppression (HIV-1 RNA <50 copies/mL). The Prescription Drug User Fee Act (PDUFA) target action dates for these two sNDAs are September 20, 2019.
Pifeltro (doravirine, 100 mg) is a novel, once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI) indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults who have no evidence of resistance to NNRTIs, either historically or currently.
Delstrigo is a three-in-one combination medication composed of fixed-dose doravirine (DOR, 100 mg), a novel non-nucleoside reverse transcriptase inhibitor (NNRTI), lamivudine (3TC, 300 mg), and tenofovir disoproxil fumarate (TDF, 300 mg). This once-daily tablet is indicated as a complete regimen for the treatment of HIV-1 infection in adults who have no evidence of resistance to NNRTIs, 3TC, or TDF, either historically or currently.
In the United States, Pifeltro and Delstrigo were approved in late August 2018 for adults with HIV-1 infection who had not previously received antiretroviral therapy. Both medications are administered orally once daily, with or without food. The labeling for Delstrigo includes a boxed warning regarding the risk of acute exacerbation of hepatitis B virus (HBV) infection following treatment discontinuation.
The submission of this sNDA is based on data from the Phase III clinical study DRIVE-SHIFT. This study was a multicenter, open-label, randomized, active-controlled, non-inferiority Phase III trial that enrolled 670 HIV-1-infected adults who had achieved virologic suppression for at least six months on an antiretroviral regimen (baseline regimen). The study evaluated the non-inferiority of switching from the baseline regimen to Delstrigo versus continuing the baseline regimen. In the study, patients were randomized into two groups: (1) the Immediate Switch Group (ISG, n=447), which switched to Delstrigo treatment on Day 0; and (2) the Delayed Switch Group (DSG, n=223), which switched to Delstrigo treatment after Week 24. The primary endpoint was the rate of virologic suppression. The primary comparison was between the virologic suppression rate in the Delstrigo ISG at Week 48 and that in the baseline regimen DSG at Week 24, followed by a comparison of the virologic suppression rates between the Delstrigo ISG and the baseline regimen DSG at Week 24.
The results showed that the Delstrigo ISG treatment group maintained virologic control at Week 48: the virologic suppression rate in the Delstrigo ISG treatment group was 90.8% (406/447) and the virologic failure rate was 1.6% at Week 48; the virologic suppression rate in the baseline DSG treatment group was 94.6% (211/223) and the virologic failure rate was 1.8% at Week 24 (treatment difference in virologic suppression: -3.8%, 95% CI: -7.9 to 0.3; treatment difference in virologic failure: -0.2%, 95% CI: -2.5 to 2.1).
Furthermore, the Delstrigo ISG treatment group maintained virologic control at Week 24: the virologic suppression rate was 93.7% (419/447) and the virologic failure rate was 1.8% in the Delstrigo ISG group at Week 24, compared with a virologic suppression rate of 94.6% and a virologic failure rate of 1.8% in the baseline DSG treatment group at Week 24 (treatment difference in virologic suppression: -0.9%, 95% CI: -4.7 to 3.0; treatment difference in virologic failure: -0.0%, 95% CI: -2.3 to 2.3).
During the 48-week treatment period, no genotypic or phenotypic resistance to the study drug was observed in patients receiving Delstrigo.
“Merck has been committed to improving the treatment and care of HIV/AIDS for decades,” said Dr. Michael Robertson, Executive Director and Head of the HIV and HCV Department at Merck Research Laboratories. “Data from the DRIVE-SHIFT study indicate that Delstrigo can serve as a new fixed-dose combination regimen for patients considering switching their antiretroviral therapy for HIV. We look forward to continuing our efforts to expand treatment options for HIV.” (Bioon.com)