ICAAC 2012: Novel NNRTI MK-1439 shows potent activity, distinct resistance profile
MK-1439 warrants further development. Preclinical data support low once-daily dosing.
The novel non-nucleoside reverse transcriptase inhibitor (NNRTI) MK-1439 exhibited good activity against a variety of HIV subtypes and maintained its potency against most common NNRTI-resistant viruses, researchers reported at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2012) this month in San Francisco.
NNRTIs are generally well-tolerated antiretroviral drugs, but emergence of resistance and cross-resistance can limit their effectiveness. In addition to a favorable resistance profile, researchers are looking for NNRTI candidates that have few drug-drug interactions, are well-tolerated, can be taken once-daily without food requirements, and can be combined into coformulations.
Ming-Tain Lai and colleagues from Merckcharacterized the antiviral activity and resistance profile of the next-generation NNRTI MK-1439 in laboratory studies.
Based on these studies, the researchers concluded that MK-1439 warrants further development and that preclinical data support low once-daily dosing.
Lai said that a Phase 2a study has been done (though he did not reveal the findings) and investigators are ready to launch a Phase 2b trial comparing MK-1439 versus efavirenz, both combined with tenofovir/emtricitabine (the drugs in Truvada), in treatment-naive individuals.
By Liz Highleyman
M Lai, M Feng, M Lu, D Hazuda, et al. Antiviral Activity andin vitro Mutation Development Pathways of MK-1439: A Novel Non-Nucleoside Reverse Transcriptase Inhibitor. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2012). San Francisco. September 9-12, 2012. Abstract H-551.