Doravirine

Bengaluru: Merck said on Wednesday its experimental oral HIV medicine was found to be non-inferior to Gilead Sciences' top-selling drug Biktarvy in a late-stage study involving previously untreated adult patients. The data showed that an oral combination regimen of doravirine and islatravir showed suppression of the HIV-1 virus at similar levels as Biktarvy at week 48, Merck said. Its safety profile was also comparable to Gilead's drug, which has become the standard of care for HIV-1 treatment . Biktarvy and Merck's drug are antiretroviral treatments , combinations of medicines used to stop reproduction of the virus. HIV-1 is the most common strain of the retrovirus that causes Acquired Immunodeficiency Syndrome, commonly known as AIDS. "Despite these positive findings, we do not anticipate today's readout to create a near-term shift in the HIV treatment paradigm," BMO Capital Markets analyst Evan Seigerman said, adding that there needs to be more "granular data" to be confident about the safety of Merck's drug. The company plans to present detailed findings from the trial at a future medical meeting and submit applications including these data to health authorities. The U.S. Food and Drug Administration is set to make its decision on approval for Merck's oral drug by April 28. While islatravir is an experimental treatment, Merck's doravirine is already approved and sold in the U.S. under the brand Pifeltro for HIV-1 treatment in combination with other antiretrovirals, and as a single-tablet regimen, Delstrigo. Islatravir is currently being tested in multiple trials in combination with other antiretrovirals for potential daily and once-weekly treatments for HIV-1. Last year, the doravirine and islatravir combination was shown to be non-inferior to Biktarvy in suppressing the replication of HIV-1 in patients who were already on antiretroviral therapy. (Reporting by Sneha S K in Bengaluru; Editing by Tasim Zahid and Leroy Leo)

Merck has identified a $5 billion-plus opportunity for its late-stage HIV portfolio. \n Merck & Co. has reported another phase 3 win for islatravir in HIV, advancing its efforts to establish the near-approval molecule as a new anchor treatment for the infectious disease.Integrase strand transfer inhibitors (INSTIs) are the backbone of current antiretroviral therapy regimens. Yet, while molecules such as Gilead Sciences\' bictegravir have cut the risk of resistance, the potential for HIV to mutate to nullify INSTIs remains a problem. Equally, drug-drug interactions, cardiometabolic toxicities and other tolerability issues associated with INSTIs are a concern for some patients. Merck is positioning islatravir as an alternative backbone for HIV drug regimens. Fresh from phase 3 wins in trials that switched patients on existing regimens to an islatravir-based treatment, Merck has reported a victory for its nucleoside reverse transcriptase translocation inhibitor in treatment-naive adults.The latest phase 3 results come from a trial that compared a combination of doravirine and islatravir (DOR/ISL) to Gilead’s three-drug, INSTI-based treatment Biktarvy. After 48 weeks of once-daily dosing, the two arms had similar proportions of patients with HIV-1 RNA levels below a certain threshold. The result caused the trial to hit its primary noninferiority endpoint.  With the trial also finding the investigational combination had a comparable safety profile to that of Biktarvy, Merck is planning to submit applications including the data to health authorities. The FDA is already reviewing a filing for approval of DOR/ISL for the treatment of HIV-1 infection in adults to replace their current antiretroviral regimen. Merck is set to receive a decision from the FDA by April 28, 2026.At an HIV investor event in July, Liz Rhee, M.D., vice president of clinical research infectious disease at Merck, said the treatment-naive data could support a label expansion in the U.S. and an initial approval application in the EU. Merck executives primarily discussed DOR/ISL as an option for the 1 in 5 patients who switch HIV regimens each year, reflecting their belief that its convenience, tolerability and low risk of drug-drug interactions will make it a go-to choice. Eliav Barr, M.D., Merck Research Laboratories’ chief medical officer, also said islatravir regimens could enable physicians to reserve INSTIs for later-line use if needed. With other trials evaluating weekly islatravir-based combinations, Merck has identified a $5 billion-plus opportunity for its late-stage HIV portfolio. Merck executives have argued that analysts underappreciate the HIV portfolio, creating an opportunity for the drugmaker to exceed expectations and partly offset threats to Keytruda if it hits its sales targets.