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Sifuvirtide [pronounced si-fu-ver-taid], is the
leading drug candidate in FusoGen's pipeline, an HIV
fusion inhibitor. Sifuvirtide has 20-fold higher
potency in vitro against HIV compared to the
marketed HIV fusion inhibitor.
Drug Design
It targets the clinically validated drug target, HIV
gp41 protein, which plays a key role in membrane
fusion through the interaction between its C-peptide
and N-peptide. The compound disrupts the interaction
by mimicking the C-peptide and binding to the
N-peptide.
Structure-based Drug Design of Sifuvirtide
Patent
The primary patent for Sifuvirtide has been issued
in China, USA, and Russia, while pending in Europe,
Japan, and other countries. Additional patent
applications have also been filed.
Potency
Sifuvirtide is the best-in-class.
Compared with the marketed HIV fusion inhibitor, which was identified
through random screening, Sifuvirtide was developed
by rational structure-based design. As shown in the
figure above, Sifuvirtide mimics the C-peptide
better than the marketed HIV fusion inhibitor, and therefore has higher
binding affinity for the gp41 N-peptide. In
addition, amino acid substitutions are introduced
into its sequence to further improve its stability
and interaction with gp41. The improved structural
design was validated by both in vitro and
in vivo studies. Compared to the marketed HIV fusion inhibitor,
Sifuvirtide has 20-fold higher inhibitory potency
(IC50
= 1.2＼0.2
nM), and much longer serum half-life in
vivo, which enables its once daily injection
regimen (compared with twice daily injections for
the marketed HIV fusion inhibitor).
Efficacy
The FS0101/02/03 trials have been completed in
China. Sifuvirtide has an excellent safety profile,
with minimal injection site reactions compared to
the marketed HIV fusion inhibitor. Its half-life is 39 hours in HIV
infected adults. After once daily subcutaneous
injection of 20 mg for two weeks, Sifuvirtide
increases patient CD4 counts, and reduces viral
loads by up to 1.2 log.
In summary, Sifuvirtide is the best-in-class, with
higher potency, less injection site reaction, more
convenient dosing schedule, and much lower cost.
These improvements can solve the major limitations
for the marketed HIV fusion inhibitor.
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