new nrti apricitabine demonstrates good safety

This is a writup from the latest Aids conf. in Mexico City
last month.
A good thumbnail on progress for reference purposes.

http://www.hivandhepatitis.com/2008icr/AIDS2008/docs/082208_c.html

New NRTI Apricitabine Demonstrates Good Safety in Early Clinical Trial

By Liz Highleyman

While new classes of antiretroviral drugs generate the most excitement, it is also important to develop new agents within the nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) class, which makes up the "backbone" of most regimens.

The novel cytidine analog apricitabine, developed by Avexa Ltd., is currently undergoing clinical trials. The existing cytidine analogs lamivudine (3TC; Epivir) and emtricitabine (Emtriva) are among the least toxic and best tolerated drugs in the NRTI class.

As previously reported, preclinical and prior clinical studies showed that apricitabine was active against HIV with the M184V mutation, which confers resistance to lamivudine and emtricitabine, and had a low propensity for mitochondrial, liver, or bone marrow toxicity.

As reported at the XVII International AIDS Conference this month in Mexico City, Avexa researchers conducted a 24-week study of apricitabine in 51 treatment-experienced HIV positive patients. A majority of participants (about 70% of the apricitabine recipients and 60% of the lamivudine recipients) were men and the mean age was about 40 years.

Participants received apricitabine (600 or 800 mg twice daily) or lamivudine (150 mg twice daily) in combination with other antiretroviral agents. The most common drugs used with apricitabine were abacavir (Ziagen), didanosine (ddI; Videx), tenofovir (Viread), atazanavir (Reyataz), lopinavir/ritonavir (Kaletra), and ritonavir (Norvir).

Results

• There were no deaths, no serious adverse events (AEs), and no discontinuations due to AEs among patients receiving apricitabine.

• 11.8% of patients in the apricitabine 600 mg arm, 16.7% in the apricitabine 800 mg arm, and 18.8% in the lamivudine arm reported any treatment-related AEs.

• The most common AEs were nausea, diarrhea, nasopharyngitis, hypertriglyceridemia, and upper respiratory tract infections, which occurred at similar rates in patients receiving apricitabine and lamivudine.

• Nasopharyngitis: 17.6% in apricitabine 600 mg arm, 11.1% in apricitabine 800 mg arm, 12.5% in lamivudine arm.

• Upper respiratory infection: 0.0%, 16.7%, and 12.5%, respectively.

• Hypertriglyceridemia: 11.8%, 5.6%, and 18.8%, respectively.

• AEs considered treatment-related were mild to moderate and were gastrointestinal (GI)-related:

• Nausea: 11.8% in apricitabine 600 mg arm, 22.2% in apricitabine 800 mg arm, 18.8% in lamivudine arm.

• Diarrhea: 23.5%, 33.3%, and 25.0%, respectively.

• Apricitabine had no significant effect on serum lipid or creatinine levels.

• No cases of rash, pancreatitis, hypersensitivity reaction, hyperlactaemia (elevated lactic acid), hyperlipasaemia (elevated lipase), or abnormal liver function tests were associated with use of apricitabine.

Based on these findings, the investigators stated that "apricitabine is safe and very well tolerated over 24 weeks in combination with other antiretroviral therapy."

There was no evidence of peripheral neuropathy, bone marrow toxicity, liver toxicity, hypersensitivity, elevated lipids, elevated lipase, or kidney toxicity, they added.

They concluded, "As a second-line drug for treatment-experienced patients, apricitabine provides antiviral activity accompanied by an excellent safety and tolerability profile."

Avexa Ltd, Melbourne, Australia and San Francisco, CA.

8/22/08

Reference
S Cox, S Moore, J Southby, and others. Safety profile of apricitabine, a novel NRTI, during 24-week dosing in experienced HIV-1 infected patients. XVII International AIDS Conference (AIDS 2008). Mexico City. August 3-8, 2008. Abstract TUAB0106.