Chimerix, Inc., a biotechnology company developing orally-available antiviral therapeutics, announced the commencement of a first-in-human study of CMX157, a novel lipid conjugate of the nucleotide tenofovir with in vitro activity against both tenofovir-sensitive and tenofovir-resistant human immunodeficiency virus (HIV). CMX157 has the potential to increase efficacy and decrease toxicity as compared to tenofovir, and may enable the creation of new 'one pill, once-a-day', fixed-dose combination regimens for the treatment of HIV infection.
The Phase 1 dose-escalating clinical study is designed to evaluate the safety, tolerability and pharmacokinetics (PK) of CMX157. Healthy volunteers will receive a single-dose of CMX157 (25 mg, 50 mg or 100 mg), a standard dose of tenofovir (as Viread®) or placebo. In addition to monitoring safety and standard PK parameters in plasma, levels of the active antiviral (tenofovir diphosphate) will be determined in peripheral blood mononuclear cells (PBMCs). These data will provide insight into the potential efficacy of CMX157, as the levels of tenofovir diphosphate in PBMCs associated with the antiviral efficacy of Viread have been documented.
"We are pleased to advance CMX157 into human clinical studies. While advances in HIV treatment have resulted in longer life spans, HIV is known to develop resistance to currently approved agents and significant drug side effects remain an issue for many patients," said Wendy Painter, M.D., MPH, Chimerix's Chief Medical Officer. "We are extremely encouraged by preclinical data that show CMX157 to be highly potent and less toxic than current HIV drugs and believe it has the potential to become an important new antiviral therapy."
CMX157 is a new chemical entity created by applying Chimerix's PIM (Phospholipid Intramembrane Microfluidization) Conjugate Technology to chemically modify tenofovir, the molecule underlying the prodrug Viread®, an antiviral agent approved for the treatment of HIV and chronic hepatitis B. Chimerix's PIM Conjugate Technology improves the absorption and distribution profile of drugs, achieving higher intracellular levels of the active antiviral agent. In vivo toxicology studies show that high plasma levels of CMX157 can be achieved with minimal toxicities.
CMX157 represents Chimerix's second antiviral compound to enter the clinic. Chimerix's lead compound, CMX001, a broad-spectrum antiviral agent with demonstrated in vitro activity against double-stranded DNA viruses, is in a multi-center Phase 2 clinical trial in stem cell transplant recipients who are seropositive for cytomegalovirus (CMV) and is also in clinical development for the treatment of BK virus in renal transplant and stem cell transplant recipients.