Avexa
Reports Positive Phase IIb Result:
Apricitabine Shows Superior Activity
March
20, 2007 VICTORIA, Australia -- Business Wire -- Australian biotechnology company
Avexa (ASX:AVX) today announced highly successful results from its Phase IIb trial
for apricitabine (ATC). ATC is Avexa's novel nucleoside reverse transcriptase
inhibitor (NRTI) being developed for the treatment of HIV infection in patients
with drug-resistant HIV.
The
Phase IIb trial compared the effectiveness of ATC in reducing the viral load of
patients with drug-resistant HIV with the effectiveness of lamivudine (3TC), a
leading NRTI in widespread use. A total of 47 patients completed 21 day dosing.
Of these, 17 patients received 600 mg doses of ATC, 16 received 800 mg doses of
ATC, and the control group of 14 patients were treated with 3TC.
The
results for patients in both ATC cohorts exceeded the Phase IIb trial primary
endpoint by a substantial margin. Patients who received ATC achieved on average
a reduction of greater than 0.8 log10 (85%) in the level of HIV in the blood after
21 days treatment compared to a reduction of less than 0.03 log10 in patients
treated with 3TC. Nine patients achieved a greater than 1.5 log10 (97%) reduction
after 21 days, with 3 patients achieving a reduction of over 2.0 log10 (99%).
Remarkably, one patient achieved a decrease in the amount of virus of more than
2.5 log10 (99.7%) after 21 days on ATC. Patients with the highest degree of drug
resistance still achieved a significant benefit from treatment with ATC. The demonstration
of superior activity in this study indicates that ATC will be an effective antiviral
drug for the treatment of many drug-resistant patients, including even those most
highly resistant.
This
is a fantastic result for Avexa," stated CEO Dr. Julian Chick. "The
positive result allows us to continue to progress ATC into Phase III trials and
towards commercialization. The team at Avexa has done a great job and these excellent
results show that their hard work has paid off."
There
were no serious adverse events (SAEs) related to the study drug, and no patients
withdrew from the study because of side effects of study drug treatment. ATC continues
to be very well tolerated, with some patients having received more than 12 months
treatment to date. Currently, there are 14 patients in the open-label section
of the Phase IIb trial and 6 patients have elected to enter into an extension
study (where they continue to be treated with ATC), having completed the full
48 weeks of the study.
"These
outstanding results clearly position ATC to become the most effective and well
tolerated NRTI for treatment of drug-resistant HIV," stated Dr. Jonathan
Coates, Avexa's CSO, and co-inventor of 3TC, a NRTI marketed by GSK.
The
emergence of resistance to antiviral drugs is one of the most important reasons
for treatment failure. No evidence of mutation in the virus resulting in resistance
to ATC was detected over the course of the treatment. This indicates that antiviral
resistance to ATC does not occur quickly and gives ATC a significant competitive
advantage over several other drugs which can rapidly select for resistance.
"Overall
the results of Avexa's Phase IIb clinical trial demonstrate that ATC is a clinically
effective antiviral drug that can significantly reduce the replication of the
virus in patients infected with drug-resistant HIV," said Chick. "Moreover,
these results demonstrate that ATC is a safe drug not associated with undesirable
side effects. There was no evidence of ATC resistant virus emerging over the trial
period. These results indicate that ATC has the properties required to position
it as the NRTI of choice for the treatment of patients failing their first line
or subsequent anti-HIV drug regimens."
Trial Design
AVX-201
is a randomized, double blind study of two doses of ATC compared to lamivudine
(3TC) in treatment-experienced HIV-1-infected patients with the M184V mutation.
Patients were randomized to receive 600mg or 800mg ATC twice daily, or 3TC twice
daily, for 21 days, in a blinded fashion. The primary endpoint of the study is
the change in the amount of virus in the blood (viral load) after 21 days treatment.
After day 21, patients continue to receive either ATC or 3TC up to week
24, but can also change their other background HIV medicines. After week 24, all
patients openly receive ATC unblinded to week 48. After week 48, patients may
elect to enter an extension study (AVX-201E) in which they continue to receive
ATC in addition to their other HIV medicines.
47 patients were analyzed
after 21 days of treatment. Approximately one third were female, and approximately
half had the highest levels of drug resistance. The majority of the patients were
recruited in Argentina, with patient ages ranging from 22 to 59.
Safety
Data
No ATC drug-related serious adverse events have been observed
to date. No patients have been withdrawn from the trial because of side effects
related to ATC treatment. In particular there has been no significant incidence
of hyperlipasemia (an indicator of pancreatitis) or elevated liver enzymes (suggestive
of liver toxicity) related to ATC. These are two serious and undesired side effects
associated with some other NRTIs. These data demonstrate the good safety profile
for ATC in the clinical setting.
Avexa,
an Australian biotechnology company, recently announced that its investigational
next-generation nucleoside reverse transcriptase inhibitor apricitabine (also
known as AVX754) demonstrated activity against HIV strains that were resistant
to 
