Doravirine/Islatravir

Dive Brief:Merck & Co. and partner Gilead Sciences on Monday reported a setback in one late-stage study in lung cancer, but success in two other Phase 3 trials testing an HIV treatment theyre working on.In one announcement, the companies said theyre halting a trial testing Gileads Trodelvy with Mercks Keytruda in frontline, non-small cell lung cancer. Study monitors found a numerical improvement in tumor progression that didnt reach significance, and determined a survival benefit was unlikely.In the other release, the partners revealed an HIV tablet combining Mercks islatravir and Gileads lenacapavir benefited people who switched off of other treatments in two Phase 3 studies. They intend to seek approval of the combination, which could be the first oral, once-weekly treatment for HIV.They didnt specify when an application might be completed, however.Dive Insight:The trio of study results appeared to impact both companies more negatively, given the high-profile nature of the setback in lung cancer.The EVOKE-03 study was another chance for Gilead to validate the hefty $21 billion purchase price it paid for Trodelvys developer Immunomedics. That treatment hasnt been as big a seller as Gilead once envisioned, and has stumbled in multiple other studies. But success in a study in frontline lung cancer, one of the most common tumor types, wouldve helped.The study was also a chance for Merck to extend its dominance in lung cancer, for which Keytruda is a pillar of care. The trial tested Trodelvy, an antibody-drug conjugate aimed at the protein TROP2, alongside Keytruda in the first-line setting. But some analysts were skeptical of the studys chances, given the way it was designed the companies didnt only focus on TROP2-expressing tumors and Trodelvys other struggles.The readout additionally carries implications for another ADC Merck is investing heavily in. Called sacituzumab tirumotecan, or sac-TMT, Merck licensed it from Kelun Biotech and has place it in a sprawling Phase 3 programthat includes 17 studies targeting a range of tumor types. Merck believes the ADC could become a cornerstone drug, and recently spotlighted results from a Phase 3 study in Chinaat the American Society of Clinical Oncology conference.Analysts and investors have been debating whether those findings might carry over to a global study in first-line lung cancer thats now underway. Merck has expressed optimism, citing certain technical differences with sac-TMT. But he EVOKE-03 results could put greater investor scrutiny on sac-TMT data coming from China until the global translation is proven, wrote Leerink Partners Daina Graybosch.Graybosch expected the stocks for both companies to trade lower given outsized investor attention on the more negative of the two announcements. Shares of Gilead dipped 3%, while Mercks stock was only slightly down.Yet the HIV findings could ultimately offset those negatives. Despite a concerted push into oncology, Gileads core business remains its HIV drugs. Its already added to that portfolio with last years approval of a preventive shot called Yeztugo. Another drug for the switch market could boost that business, as some 20% of patients change treatment regimens each year, Graybosch wrote.The positive results also amount to another win for Mercks HIV franchise this year, following the April approval of Idvynso,RBC Capital Markets analyst Trung Huynh wrote in a separate note. '

Gilead Sciences and Merck & Co. began the week with a mixed clinical scorecard.In back-to-back announcements Monday, the partners revealed they are discontinuing a Phase III study testing Gilead's TROP2-directed antibody-drug conjugate (ADC) Trodelvy (sacituzumab govitecan-hziy) in combination with Merck's Keytruda (pembrolizumab) in lung cancer, while at the same time touting the success of their experimental once-weekly HIV pill in two other late-stage trials.The oncology setback throws a wrench into Gilead's expansion plans for Trodelvy, which is currently approved for two forms of breast cancer and for urothelial cancer. Lung cancer is a key target, but success so far has been uneven; the Phase III EVOKE-01 trial testing the TROP2 ADC as monotherapy against docetaxel in second-line non–small-cell lung cancer (NSCLC) failed in 2024.'Numerical improvement'Meanwhile, the earlier mid-stage EVOKE-02 trial suggested that combining the drug with Keytruda could be promising in newly diagnosed patients, but that momentum doesn't appear to have carried into Phase III. As a result, the companies have decided to halt the EVOKE-03 trial (also known as KEYNOTE-D46).The study, which was testing the combo against Keytruda monotherapy, enrolled previously untreated metastatic NSCLC patients whose tumours expressed high levels of PD-L1. The decision followed a review by an external data monitoring committee, which found that although the Trodelvy-Keytruda combination produced a "numerical improvement" in progression-free survival, it failed to achieve statistical significance. The committee also concluded that the probability of achieving a significant overall survival benefit at the final analysis was "unlikely." No new safety signals were identified.The companies said there are no changes to other ongoing Trodelvy or Merck studies. The Trodelvy-Keytruda pairing was tested in the triple-negative breast cancer ASCENT-04 and ASCENT-05 studies in the first-line metastatic and high-risk adjuvant settings, respectively.Non-inferiority to Biktarvy, ARTWhile the oncology programme stumbled, Gilead and Merck delivered more encouraging news involving their ongoing HIV partnership.The investigational once-weekly single-tablet regimen combining Gilead's capsid inhibitor lenacapavir with Merck's islatravir, a nucleoside reverse transcriptase translocation inhibitor, met the primary endpoint in both Phase III ISLEND-1 and ISLEND-2 studies of virologically suppressed patients at week 48.In ISLEND-1, the regimen was found to be statistically non-inferior to Gilead's Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide), while ISLEND-2 showed non-inferiority against a range of standard-of-care daily oral antiretroviral therapy (ART) regimens. Safety findings were generally similar to the comparator treatments.The companies said they intend to file the data with regulators around the world for what could become the first once-weekly oral treatment option for people with HIV.Lenacapavir is already on the market as Sunlenca for multi-drug-resistant HIV and Yeztugo as a twice-yearly preventive shot. In April, the FDA approved a once-daily single-tablet regimen combining islatravir with doravirine under the name Idvynso for adults with virologically suppressed HIV-1.