Merck & Co announced today that it has halted a phase III study comparing once-daily dosing of the company’s HIV integrase inhibitor raltegravir to the standard twice-daily dose, on the recommendation of the trial's independent Data Safety Monitoring committee.
Although once-daily raltegravir (Isentress) did not prove statistically inferior to twice-daily raltegravir, fewer patients in the once-daily arm had a viral load suppressed below 50 copies/ml after 48 weeks of treatment.
This difference was chiefly driven by poorer viral suppression among people with high baseline viral loads (above 100,000 copies/ml), the company said in a press release.
The study randomised participants new to HIV treatment to receive 800mg of raltegravir once daily or 400mg of raltegravir twice daily, in combination with Truvada (tenofovir/FTC).
Among all participants (n=770), 83.2% of the once-daily group had viral load below 50 copies/ml at week 48, compared to 88.9% of the once-daily group. This difference (-5.7%) was within the pre-defined 95% confidence intervals (-10.7% - -0.83%).
However, among participants with baseline viral load above 100,000 copies/ml (n=304), the difference was greater. While 84.2% of the twice-daily raltegravir group had a viral load below 50 copies/ml within this viral load stratum by week 48, the proportion with fully suppressed viral load in the once-daily group was 74.3%.
Following an initial analysis of the data the trial’s Independent Data Monitoring Committee recommended that all patients in the once-daily arm should be switched to twice-daily raltegravir, and Merck & Co decided to halt the study.
Raltegravir is the first of a new class of antiretroviral drug, called integrase inhibitors, which block the integration of HIV’s genetic material into immune system cells. Raltegravir is currently licensed for twice-daily dosing in the United States and European Union, and is one of the recommended options for first-line antiretroviral therapy in US treatment guidelines.
A number of other companies are developing once-daily integrase inhibitors.
Gilead is currently testing elvitegravir, a once-daily integrase inhibitor that will be boosted with ritonavir or with Gilead’s own proprietary boosting agent, cobicistat. A phase III clinical trial of a pill combining elvitegravir, cobicistat, tenofovir and FTC is currently underway.
Another once-daily integrase inhibitor is being developed by Viiv Healthcare and Shionogi Pharmaceuticals, and has just entered phase III trials.