26 October 2021 - - US-based pharmaceutical company Merck (NYSE: MRK) has posted positive top-line results from two pivotal Phase 3 trials of the investigational, once-daily oral fixed dose combination pill of doravirine/islatravir (DOR/ISL) in adults with HIV-1 infection who are virologically suppressed on different antiretroviral therapy regimens (ART; ILLUMINATE SWITCH A) or bictegravir/emtricitabine/tenofovir (BIC/FTC/TAF; ILLUMINATE SWITCH B), the company said.

At 48 weeks, both trials met their primary efficacy endpoint of percentage of participants with HIV-1 RNA levels ≥50 copies/mL, demonstrating that antiviral efficacy was comparable between DOR/ISL and ART (ILLUMINATE SWITCH A) and between DOR/ISL and BIC/FTC/TAF (ILLUMINATE SWITCH B).

The safety and tolerability profile of DOR/ISL during the trials to date are consistent with the previously reported Phase 2 studies.

Doravirine is approved for the treatment of adults with HIV-1 in combination with other antiretrovirals, as a single agent (Pifeltro) and a component of a single-tablet regimen (Delstrigo; DOR/3TC/TDF).

Islatravir is Merck's investigational nucleoside reverse transcriptase translocation inhibitor under evaluation for the treatment of people living with HIV-1 infection in combination with other antiretrovirals.

Detailed findings from these studies will be presented at a future scientific congress and will form the basis of global regulatory applications.

The ILLUMINATE clinical trial program is evaluating DOR/ISL in a broad patient population, which includes people with HIV-1 who are virologically suppressed on ART, those who are heavily treatment experienced and those who are new to HIV treatment.

The clinical trial program also includes pediatric participants with HIV-1 weighing at least 35 kg who are virologically suppressed and have not previously been treated.

Merck is committed to enrolling diverse people in our HIV-1 clinical trials, especially among communities who may be disproportionately impacted by HIV, such as women and those within the Black and Latinx communities.

Pifeltro (doravirine, 100 mg) is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine.

Delstrigo (doravirine, 100 mg/lamivudine 300 mg/tenofovir disoproxil fumarate, 300 mg) is indicated as a complete regimen for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of Delstrigo.

Delstrigo contains a boxed warning regarding post-treatment acute exacerbations of hepatitis B infection. See Selected Safety Information below.

Pifeltro and Delstrigo are contraindicated when co-administered with drugs that are strong cytochrome P450 3A enzyme inducers (including the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, and phenytoin; the androgen receptor inhibitor enzalutamide; the antimycobacterials rifampin and rifapentine; the cytotoxic agent mitotane; and the herbal product St. John's wort (Hypericum perforatum)), 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 lamivudine.

Renal impairment, including cases of acute renal failure and Fanconi syndrome, have been reported with the use of TDF. Delstrigo should be avoided with concurrent or recent use of a nephrotoxic agent (eg, high-dose or multiple NSAIDs).

Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in patients with risk factors for renal dysfunction who appeared stable on TDF.