Tibotec to seek once-a-day Prezista regimen for experienced patients
This article was originally published in Scrip
Tibotec (Johnson & Johnson) has shown that a once-daily regimen of its HIV protease inhibitor Prezista (darunavir) is non-inferior to a twice-daily dose in suppressing viral load in treatment-experienced HIV-1 infected patients in a Phase III study.
The data were presented last week at the Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco.
Tibotec plans to file the data on the study, which is known as ODIN, in the EU and US with the aim of getting the once-daily regimen approved for treatment-experienced patients. A twice-daily, ritonavir (Abbott's Norvir)-boosted regimen is already approved for these patients, whereas a once-daily regimen is approved for patients who are treatment-naïve.
The company says the main advantage with the once-daily dosing is improved convenience as well as a reduction in adverse events.
"Once-daily dosing is now the treatment paradigm for HIV, even treatment-experienced patients would like once-daily dosing," said Dr Perry Mohammed, medical lead for virology at Tibotec.
The current recommended dose of Prezista plus ritonavir for treatment-experienced patients is 600/100mg twice daily. For treatment-naïve patients, the recommended regimen is already 800/100mg once-daily. The company hopes to be allowed to market the same once-daily dose in both patient populations.
The doses of darunavir and ritonavir are not available in a combined pill formulation, but are instead taken separately.
"We would like to combine them in the future," added Dr Mohammed.
The non-inferiority ODIN study randomised 590 treatment-experienced patients with no darunavir-associated mutations to receive either Prezista/ritonavir 800/100mg once daily or Prezista/ritonavir 600/100mg twice daily. Patients had HIV RNA levels of >1,000copies/ml and CD4 counts of >50cells/mm3 and also received an optimised background regimen of at least two nucleoside reverse transcriptase inhibitors. According to Dr Mohammed, some patients were taking another drug in addition to the conventional three-drug anti-retroviral regimen because efficacy of this regimen declines with time.
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Tibotec is now investigating the effect of a once-daily regimen on the emergence of viral strains that are resistant to Prezista. However, Dr Mohammed doubts that once-daily dosing will increase resistance. "If it is suppressing the HIV viral load, it is also suppressing resistance-mediated mutations," he commented.
The incidence of adverse events was lower in the once-daily arm than the twice-daily arm (5.4% versus 9.1%). There was no significant difference in incidence of grade 2 to 4 (moderate to severe) adverse events between the two groups.
The incidence of lipid and liver abnormalities with once-daily treatment compared with twice-daily treatment was 5.2% versus 11.0% for triglycerides, 10.1% versus 20.6% for total cholesterol, 9.8% versus 16.7% for cholesterol and 1.7%/2.1% versus 3.5%/3.5% for alanine aminotransferase/aspartate aminotransferase (ALT/AST) levels.