Merck is uniquely positioned in the evolving HIV treatment field with the first to market novel islatravir and FDA approval of Idovinso, a combination therapy that is the cornerstone of the company’s lucrative HIV franchise.
Idovinso is a once-daily oral combination drug of Merck & Co.’s doravirine and islatravir. Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that has been commercialized since 2018 as part of Merck’s Pifertro and Delstrigo, while islatravir is a new nucleoside reverse transcriptase translocation inhibitor (NRTTI) that represents the “anchor drug” in many of the company’s other HIV combos.
Merck said in an April 21 press release that the debut of the combination of doravirine and islatravir is specifically targeted at patients switching from other HIV treatments and will be available in pharmacies starting May 11.
The FDA on Monday approved the drug for approval as an HIV treatment to replace a patient’s current antiretroviral therapy in adults who are virologically suppressed and have no history of treatment replacement due to virologic treatment failure or doravirine resistance. Viral suppression is the goal of antiretroviral HIV therapy, meaning that a patient’s HIV viral load is low enough that it is undetectable by standard tests or cannot be transmitted to sexual partners.
Two Phase 3 trials tested the drug in patients on baseline antiretroviral therapy and those whose HIV was being managed with Gilead’s lead Biktarvy. Merck said the study showed Idovinso was non-inferior to both comparators and offered a “nearly equivalent” safety profile. The trial is part of a new drug application that Merck filed in July, and the new approval comes one week earlier than the FDA’s previously set April 28 decision date.
In one study, people who switched from Biktarvy to Idvynso saw “minimal changes” in weight and body composition, Merck reported in October. These are two common concerns that are often central to people living with HIV, Chloe Orkin, MD, of Queen Mary University of London, commented at the time.
“As the only two-drug, non-INSTI, tenofovir-free regimen, Idovinso expands treatment versatility beyond currently available oral treatment options,” Eliav Barr, MD, chief medical officer at Merck Research Laboratories, explained in an approval press release. “As the health needs of adults living with HIV change over time, Idovinso offers clinicians a new option for treating HIV. This approval marks an important new chapter in Merck’s long-standing commitment to research and discovery for people living with HIV.”
Idvynso enters the HIV treatment market dominated by integrase strand transfer inhibitors (INSTIs). INSTIs are a popular antiretroviral drug class that includes molecules used by Gilead’s Biktarvy and GSK’s Dovato, among others. However, INSTIs are associated with resistance mechanisms that may place users at risk of uncontrolled HIV infection.
At an investor event last year, Merck executives said they believed the company’s Idovinso had the potential to become the go-to option for the 1 in 5 patients who switch HIV treatments each year, given its benefits of convenience and tolerability, as well as the low risk of drug-drug interactions. However, Merck notes in a release that Idovinso is contraindicated when used with certain drugs, including certain enzyme inducers.
Still, Merck has been testing islatravir in multiple patient populations for years, so there’s likely more to come for new entrants to the HIV market.
Last fall, the company reported that its combination of doravirine and islatravir met criteria in a Phase 3 trial evaluating efficacy in previously untreated patients, demonstrating non-inferiority to once-daily oral Biktarvy.
Like other Merck investigational HIV treatments, islatravir is being studied in combination with Gilead’s lenacapavir as a potential once-weekly combination therapy. This cocktail has already been shown to be able to sustain viral suppression in patients who have switched from another treatment.
Merck has been at the forefront of HIV scientific research since 1985, according to the company. As the patent cliff for its best-selling cancer drug Keytruda looms closer, Merck is relying on future HIV sales as a key spoke in its infectious disease drug portfolio, which could represent a $15 billion opportunity by the mid-2030s, the company said in a recent presentation. Merck expects a small number of new growth drivers across therapeutic areas to deliver potential annual revenues of more than $70 billion per year by then.
