Doravirine/lamivudine/tenofovir disoproxil fumarate

Merck's Idvynso (doravirine/islatravir) marks the commercial introduction of the company's islatravir, a novel HIV treatment option that's being studied in a number of other combinations. Merck is carving out its own place in the evolving HIV treatment space with an FDA approval for its Idvynso, a combination regimen that brings its novel islatravir to market for the first time and serves as the cornerstone of what could be a lucrative HIV franchise for the company. Idvynso is a once-daily, two-drug oral pairing of Merck’s doravirine and islatravir. Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that has been commercialized since 2018 as part of Merck’s Pifeltro and Delstrigo, while islatravir is a newer nucleoside reverse transcriptase translocation inhibitor (NRTTI) that represents the “anchor medicine” in a number of other HIV combos that the company is advancing.The doravirine and islatravir combo’s debut is specifically targeted at patients who are switching from other HIV treatments and will be available in pharmacies after May 11, Merck said in its April 21 press release. The FDA signed off on the drug Monday as an HIV treatment to replace patients’ current antiretroviral regimens among adults who are virologically suppressed and who have no history of virologic treatment failure or treatment substitutions due to doravirine resistance. Viral suppression is the goal of antiretroviral HIV therapy and means that a patient’s HIV viral load is low enough that it can’t be detected by standard tests or transmitted to sexual partners. A pair of phase 3 studies tested the drug in those on a baseline antiretroviral therapy and those who manage their HIV with Gilead’s leading Biktarvy. The studies showed that Idvynso was non-inferior to both comparators while offering a “generally comparable” safety profile, Merck said. The trials formed part of a new drug application Merck filed in July, with the new approval coming a week ahead of the April 28 decision date the FDA had previously set. In one study, those who switched from Biktarvy to Indvynso saw “minimal changes” in weight and body composition, Merck reported in October. Those are two common concerns that can often be central for those living with HIV, Queen Mary University of London’s Chloe Orkin, M.D., commented at the time.  “As the only two-drug, non-INSTI, tenofovir-free regimen, Idvynso expands therapeutic diversity beyond the currently available oral treatment options,” Eliav Barr, M.D., chief medical officer at Merck Research Laboratories, explained in the approval press release. “As the health needs of adults living with HIV change over time, Idvynso gives clinicians a new choice for HIV treatment. This approval marks an important new chapter in Merck’s long-standing commitment to research and discovery for people living with HIV.” Idvynso enters an HIV treatment market populated by integrase strand transfer inhibitors (INSTIs), a popular antiretroviral drug class that includes molecules used in Gilead’s Biktarvy and GSK’s Dovato, to name a few. However, INSTIs have been associated with resistance mechanisms that can leave users at risk of unsuppressed HIV. With benefits in convenience and tolerability coupled with a low risk of drug-drug interactions, Merck is confident that its Idvynso could make for a go-to choice for the 1 in 5 patients who switch HIV regimens each year, company executives noted at an investor event last year. That said, Idvynso is contraindicated when co-administered with specific drugs such as certain enzyme inducers, as specified by Merck in its release. Still, much more is to come for the new entrant to the HIV market, as Merck has long been busy testing out islatravir across several patient populations. Last fall, the company reported that its doravirine-islatravir combo met the bar in a phase 3 trial evaluating its benefits across treatment-naïve patients, demonstrating non-inferiority to once-daily oral Biktarvy. Elsewhere, as well as being studied with other investigational Merck HIV treatments, islatravir has been paired with Gilead’s lenacapavir as a potential once-weekly combo therapy. That cocktail has already proven that it can sustain viral suppression in patients who switched from another therapy. Merck has been at the forefront of HIV scientific research since 1985, the company says. With the patent cliff for top-selling cancer drug Keytruda creeping closer, Merck is relying on its future HIV sales as a key spoke of its infectious disease drug portfolio, which could represent a $15 billion commercial opportunity by the mid-2030s, the company said in a recent presentation. Merck expects its handful of new growth drivers across therapeutic areas to deliver potential annual revenue of more than $70 billion by that time.

The FDA on Tuesday approved Merck & Co.'s Idvynso, a once-daily single-tablet regimen combining doravirine and islatravir for adults with virologically suppressed HIV-1, expanding options for patients switching off existing antiretroviral (ARV) therapies. The clearance came a week ahead of its April 28 decision date.The drug is specifically indicated for patients with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine."As the only two-drug, non-INSTI [integrase strand transfer inhibitor], tenofovir-free regimen, Idvynso expands therapeutic diversity beyond the currently available oral treatment options," said Eliav Barr, chief medical officer at Merck Research Laboratories.Doravirine, a non-nucleoside reverse transcriptase inhibitor, is already approved as Pifeltro and as part of a fixed-dose tablet marketed as Delstrigo (doravirine/lamivudine/tenofovir), while islatravir belongs to a new ARV class known as nucleoside reverse transcriptase translocation inhibitors.Merck's filing was based on two Phase III trials that enrolled more than 1000 patients across switch settings.In the MK-8591A-052 study, 1% of patients switched to Idvynso had viral loads ≥50 copies/mL at week 48, compared with 1% of those who remained on Gilead Sciences' once-daily, single-tablet Biktarvy, which combines three drugs: bictegravir, emtricitabine and tenofovir alafenamide. Viral suppression rates, a secondary endpoint of the study, were 92% and 94%, respectively.The second study, known as MK-8591A-051, involved patients switching from a range of ARV regimens, and showed that 1% of those on Idvynso had a viral load of ≥50 copies/mL at week 48 versus 5% on baseline therapy, while 96% maintained suppression versus 92% in the control group.Last year, Merck reported results from a third Phase III trial dubbed MK-8591A-053 showing that its tablet was non-inferior to Biktarvy in treatment-naïve adults with HIV.