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.
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