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Merck today revealed positive results from two Phase III trials on a potential treatment for adults with HIV-1 infection and are virologically suppressed on different antiretroviral regimens (ART).
The two Phase III studies are part of the ILLUMINATE clinical trial, which looks into the action of doravirine/islatravir (DOR/ISL) on HIV-1. The first trial evaluated DOR/ISL on patients on different ARTs (ILLUMINATE SWITCH A), while the second looked into the effect of DOR/ISL on those who virologically suppressed on bictegravir/emtricitabine/tenofovir (BIC/FTC/TAF, ILLUMINATE SWITCH B). The participants include adults and pediatric patients weighing at least 35 kg, virologically suppressed, and who have not yet received treatment.
After 48 weeks, the researchers found that both met their primary endpoint of efficacy, with HIV-1 RNA levels higher than 50 copies/mL, indicating antiviral efficacy. Tolerability and safety remained consistent with previous studies.
Doravirine is already approved for use in adults with HIV-1 alongside other ARTs either by itself (PIFELTRO) or as a component of a single-tablet drug (DELSTRIGO; doravirine/lamivudine/tenofovir disoproxil fumarate). Islatavir is Merck's product, which is still under evaluation for the said indication. Results from these two studies are essential in Merck's future application to regulatory authorities. Aside from the ILLUMINATE program, Merck is also testing islatravir under the IMPOWER clinical trial as pre-exposure prophylaxis of HIV-1 infection.
"We are encouraged by the results from the Phase III ILLUMINATE SWITCH A and B trials, in which the DOR/ISL dual regimen efficacy was comparable to certain commonly used three-drug regimens. We will continue to study doravirine/islatravir in diverse populations of people living with HIV and look forward to sharing data from these trials," said Dr. Joan Butterton, the vice president of global clinical development for infectious diseases at Merck Research Laboratories, in a statement.
ILLUMINATE SWITCH A evaluates the effect of 100mg/0.75mg of DOR/ISL on 672 participants when taken once daily for up to 96 weeks. Endpoints were assessed at week 48. ILLUMINATE SWITCH B looks into 100mg/0.75mg or DOR/ISL of 641 participants when taken once a day up to 144 weeks. Endpoints were evaluated at week 48 too.
All patients should be tested for hepatitis B (HBV) before starting ARV therapy to prevent any adverse reactions. Anti-HBV therapy may be initiated if necessary. Some components of the two drugs might also be contraindicated to certain pre-existing conditions and medications. For one, as DELSTRIGO is a complete regimen, it should not be co-administered with other antiretroviral drugs for treating HIV-1 infection.
PIFELTRO and DELSTRIGO are not advised to be used with medications that contain strong cytochrome P450 (CYP)3A enzyme inducers, including anticonvulsants oxcarbazepine, carbamazepine, phenytoin, and phenobarbital. They also shouldn't be used with the herbal product St. John's wort.