Chemistry Reference
In-Depth Information
development. Panacos has named the compound Bevirimat and lists it as the lead
antiviral product of the company.
During 2004, two Phase I studies and a Phase I/II study of
M3
were completed.
In the Phase I studies, the drug was well tolerated and showed good anti-HIV
levels in the body. In the Phase I/II study,
M3
showed activity in HIV-infected
patients and significantly reduced viral blood levels (known as viral load) (122,
123). Another 2004 milestone was that the U.S. Food and Drug Administration
(FDA) granted Fast Track Status for
M3
.
The Phase IIa study demonstrated the antiviral potency of
M3
, following once-
daily oral dosing for 10 days in HIV-infected subjects not on other antiretroviral
therapy. Viral load was reduced significantly compared with placebo. On day 11,
following complete dosing, the median reduction at the 200-mg dose was a 91%
decrease. In the Phase IIa trial,
M3
was well tolerated, all adverse experiences
were mild or moderate, and no dose-limiting toxicity was identified (122, 123).
Subsequently, studies have shown that
M3
can be administered successfully
in a tablet form rather than by an oral solution. Also, two drug interaction
clinical trials of
M3
, in combination with the approved HIV drugs ritonavir
and atazanavir, have been completed and showed little likelihood of significant
adverse drug-drug interactions when used in combination therapy (124).
In summary,
M3
shows potent viral load reduction, a strong safety profile (with
no evidence of organ toxicity or clinical intolerance), no evidence of clinically
significant drug interactions, and, quite importantly, no evidence of rapid resis-
tance development, which is a primary cause for antiretroviral treatment failure
(125-127)
Phase IIb clinical trials began in 2006 and still are ongoing. One of the trial
goals will be to determine an optimal dose of
M3
. These trials will involve HIV-
infected patients who are failing current therapy and will be randomized, blinded,
and placebo-controlled (124).
In Phase III clinical trials targeted for 2007/2008, combination therapy studies
will be performed in a total of 300 to 500 patients at a commercial dose. The
target for New Drug Application (NDA) is 2008/2009 (124). The efficient clinical
trials progress of
M3
continues to mark it as a leading new treatment for AIDS.
14.3 ACTIVE COMPOUNDS ISOLATED FROM WELL-KNOWN
FOLKLORIC MEDICINE
In addition to anticancer and anti-HIV agents, various types of active compounds
that are active against other diseases and disorders (e.g., malaria, inflammation,
and so forth.) also have been isolated from natural sources, especially well-known
folkloric medicine. These compounds and their plant sources are described below.
14.3.1 Artemisia annua (qinghao, artemisinin derivatives)
Qinghao (Sweet Wormwood) is the dried aerial parts of the herb
Artemisia annua
L. (Asteraceae family), which has been used in China for centuries to treat fever
