Transcript Protease inhibitor Phase 3 Intercell Novartis IC41 Therapeutic

• Only infects humans and chimpanzees
• This is a virus that mainly affects the Liver
– Asymptomatic
• Only lives for about 16 hours outside the
human body.
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Ribonucleic acid (RNA)
10,000 units called nucleotides
family Flaviviridae and genus hepacivirus
40 to 60 nanometers in diameter
six major genetic types (genotypes) and many
more subtypes
– genotype 1 (1a and 1b), which accounts for 80% of
hepatitis C virus cases in the U.S.
– patients infected with genotypes 2 or 3 are much
more likely to respond to interferon therapy. In
contrast, patients infected with genotype 1
(particularly 1b) or genotype 4 do not respond very
well to interferon therapy
• More than 4 million Americans (1.3% of the
U.S. population) and 170 million individuals in
the world (3% worldwide)
•Drug use
•Through injection
•Sharing needles, spoons, cotton, water,
etc.
•Also nasal inhalation
•Cocaine and Crystal Methamphetamine
•Blood products
•Organ transplants
•Blood transfusion
•prior to implementation of HCV
screening
•In the U.S., this would refer to
procedures prior to 1992
•Sexual activity
•Rarely transmitted in this fashion
•Spouses are encourage to use a condom
•Food
•Rarely transmitted in this fashion
•Even during kissing it is hard to obtain the
virus. (unless and open sore is present)
•Hygiene
•It is also not recommended that you share
toothbrushes.
•Early signs:
•fatigue, weight, retention of urine, muscular
aches, poor appetite,
•Hepatitis C is most readily diagnosed when
serum aminotransferases are elevated and antiHCV is present in serum. The diagnosis is
confirmed by the finding of HCV RNA in serum
• apolipoprotein complexes
• low-density lipoprotein receptor
(LDL-R)
• glycosaminoglycans (GAGs)
• On Cell Surface
• CD81
• scavenger receptor class B type 1 (SRB1) development
• CLDN1
• The HCV accumulates in the liver.
– Caused by human immune systems response to
the HCV
• includes cytotoxic (injurious to cells)
• lymphocytes
• specific inflammatory messengers (cytokines).
• HCV causes the following changes in liver
tissue:
• Necrosis and inflammation at the edge of the
portal areas, so-called “piecemeal necrosis” or
“interface hepatitis”
• Necrosis of hepatocytes and focal
inflammation in the liver parenchyma
• Inflammatory cells in the portal areas (“portal
inflammation”)
• CYP2E1, an enzyme involved in the
breakdown of alcohol in the live
• breaks down potentially toxic
foreign substances (i.e.,
xenobiotics), including alcohol.
• Enhanced activity results in the
increased generation of
acetaldehyde from alcohol, free
radicals (e.g., superoxide [O2.] and
hydroxyl [OH.]) that can cause liver
injury by promoting excessive
breakdown of fat molecules (i.e.,
lipid peroxidation).
• free radicals most likely potentiate
the HCV-associated oxidative
stress and the resulting liver
damage
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By itself, ribavirin has little effect on HCV
Used in como with interferon
Rabavirin tab 200mg
2 times a day 2 pills each time
Side effects
– anemia, fatigue, insommia depression, hair
loss. nausesa & loss of appetite
• improvements in serum ALT levels &
detectable HCV RNA in up to 70 percent of
patients
• 48-week course
• Only 55% remain HCV Free
• protein NS5B is cleaved from the HCV polyprotein by the NS3
serine protease, and functions as a RNA-dependent RNA
polymerase
– nucleoside polymerase inhibitors
• inhibit the active site causing chain termination (for example,
valopicitabine (NM-283), MK-0608, R1626, PSI-6130 and its
prodrug R7128),
– non-nucleoside polymerase inhibitors
• allosteric inhibition resulting in a conformational change of the
protein (for example, BILB 1941 and HCV-796)
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Company
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Vertex
Vertex
Vertex
Schering
Intercell Novartis
Chiron / CSL
Roche
Intermune / Roche
Roche / Pharmasset
Roche / Medivir
Medivir / Tibotec
Medivir / Tibotec
Pfizer
Benitec / Tacere Bio / Pfizer
ViroChem Pharma
ViroChem Pharma
ViroChem Pharma
Globeimmune
Drug
Development Phase
Telaprevir (VX-950) Protease Inhibitor
VX-500 protease inhibitor
VX-813 2nd gen protease inhibitor
Boceprevir (SCH503034) Protease inhibitor
IC41 Therapeutic Vacccine
Therapeutic Vaccine CSL123
R1626 Polymerase inhibitor
Protease inhibitor ITMN-191 R7227
R7128 nucleoside polymerase inhibitor
HCV polymerase inhibitor
TMC435 Protease inhibitor
polymerase inhibitor
PF-868554 Non-Nuc Polymerase inhibitor
RNA interference TT033
VCH-759 Non nuc Polymerase inhib
Polymerase inhib
Polymerase inhib
GI 5005 Therapeutic Vaccine
Phase 3
Phase 1
Pre Clinical
Phase 3
Phase 2
Phase 2
Phase 2
Phase 1
Phase 1
R&D
Phase 2
R&D
Phase 2
Pre Clinical
Phase 2
Pre Clinical
R&D
Phase 2
• Telaprevir, also known as VX-950 is an oral
Protease Inhibitor (NS3-4A). It is being
developed by Vertex Pharmaceuticals for the
treatment of hepatitis C virus.
• Patients with Genotype 1 Hepatitis C support
potential to shorten treatment duration in
treatment-naïve, genotype 1 HCV patients.
• IC41 is a therapeutic peptide vaccine. It is
being developed by Intercell AG for the
treatment of hepatitis C.
The vaccine consists of five synthetic peptides
(IPEP83, 84, 87, 89,1426) harboring HCV CD4
and CD8 T-cell epitopes and the synthetic
adjuvant poly-L-arginine.
• Milk Thistle
– Flowering plant from Europe
– Said to repair and prevent liver damage.
• Alpha Lipoic
– antioxidant
– Used in body to create energy
• Millions of people are infected.
• Causes damage to the liver.
• Several different genotypes (1 most common
in U.S.)
• Several treatment options
• Hard to transfer the virus
• A vaccine is in Phase 2 trails
1. http://www.viziereurope.org/IMG/pdf/RDeFrancesco_VIZIER_2007.pdf
2. http://digestive.niddk.nih.gov/ddiseases/pubs/chronichep
c/
3. http://www.nature.com/nrd/journal/v6/n12/full/nrd2411
.html
4. http://www.hcvdrugs.com/forum/list.php?17
5. http://journals.elsevierhealth.com/periodicals/ygast/articl
e/S0016-5085(08)02048-9/abstract
6. http://en.wikipedia.org/wiki/Hepatitis_C
7. www.abbottmolecular.com/HepatitisCDemographic...
8. http://en.wikipedia.org/wiki/Milk_thistle