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1 shot TT-034 multi-drug hep C cure USA trial NC

I am trying to understand how this new one shot treatment for HCV works. Phase I/IIa clinical trial for TT-034 expected to start in March, 2014 at Duke Clinical Research Unit in North Carolina.  Maybe we will see someone posting here in the next month or so that's in this trial.

If it's successful I wonder how much will it be? What effect will it have on the new meds and stock prices of the other companies like Gilead.  

University of Westminster develops groundbreaking method to test hepatitis C cure

Researchers at the University of Westminster have developed a groundbreaking method which can be used to test a new innovative cure for hepatitis C, a liver disease caused by the hepatitis C virus (HCV).

Biomedical Sciences 17 February 2014
The cure is the first of its kind ever to be tested in humans and comes in the form of a drug based on gene therapy which is under development by the Australian company Benitec Biopharma.

Although treatments are already available for hepatitis C, these are lengthy, have low chances of success, cause significant side-effects, or the virus is already becoming resistant. The new drug, TT-034, developed by Benitec Biopharma, is based on the biological mechanism for which the Nobel Prize in Physiology or Medicine was awarded in 2006. Unlike anything else currently available to patients, this treatment works with a single injection to directly destroy the hepatitis C virus and remove the infection. The drug is currently undergoing clinical trials in the US with results expected in the coming months.

Deep Sequencing Insights in Therapeutic shRNA Processing and siRNA Target Cleavage Precision



Benitec Biopharma (ASX:BLT) has responded to a speeding ticket from the ASX, saying that it is not aware of any undisclosed information that could explain the recent surge in its share price.
The company received an ASX price query yesterday, when its share price rose to end the day at $1.26 a share from Wednesday's close of $0.99. It's share price has gone up over 72% in the last one month.

Benitec had earlier this week said that patient screening for the Phase I/IIa clinical trial for TT-034 Hepatitis C drug was on track at the Duke Clinical Research Unit in North Carolina with the first dosing expected to occur in early to mid March 2014.

Preclinical studies have shown that the vector used to deliver the TT-034 specifically targets liver cells where it transfects almost every cell without causing toxic effects. The drug is designed to prevent development of viral resistance, which is a major problem
7 Responses
446474 tn?1446347682
How it works?

It is an attempt to use the natural immune system response of RNA interference (RNAi) to block the replication of HCV in the liver by regulating certain genes. Here is a video explaining RNAi for the laymen...

This is my best explanation of how this would work with hepatitis C...
When the HCV virus invades a liver cell it begins to make copies itself (that is the main function of all viruses) as quickly as it only lives for hours. For the virus to make copies of itself it uses RNA to copy and distribute itself. When the virus is in this part of its viral life-cycle its RNA is double-stranded and long. What this treatment will attempt to do is have an enzyme that is called a 'Dicer' chop up (gene-splicing) any double-stranded RNA it finds into small bits that a group of proteins then can then unwind, leaving only one strand which the proteins can then carry away. The proteins than will look for any other RNA that has the same code as the one it is carrying and then bind to it. The binding process then leads to partial or full blockage of the virus RNA protein production. This stops the virus from replicating and spreading to more liver cells. Without replication the virus will quickly die off preventing the liver damage that occurs each time the virus replicates. Undetectable viral load and no further liver damage.

This would be an additional approach to the current DAA approach of stopping viral replication by interfering with the nonstructural region codes for the polypeptides NS2, NS3, NS4A, NS4B, NS5A, and NS5B. For example Sovaldi is a NS5B polymerase inhibitor.


Avatar universal
First received: July 8, 2013 Last updated: January 20, 2014 recruiting has started
Official Title: A Phase I,II Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of Single Doses of TT-034 for Subjects With Chronic Hepatitis C (CHC) Infection
Subjects must a history of chronic HCV infection defined as documented HCV genotype 1 infection for at least 6 months.
among other requirements
Baseline HCV RNA level of > 100,000 IU/mL and:No evidence of cirrhosis at  Screening At least 3 months since prior therapy for HCV A willingness to enroll in a 5 year follow-up safety study
Many exclusions to limit HCV patients to those in the best overall heath.

Duke Clinical Research Institute Durham, NC Recruiting
UCSD Antiviral Research Center an Diego Ca Not yet recruiting
contact info at the above link.

Phase 1 can be risky but someone has to go first. Phase 2a risk is a little lower. If you are considering please become well informed about the risks, If offered the trial after consulting with your hepatitis doctor make your own decision.

So it will be some time before we will see results. If successful then more phase 2b and/or 3 studies with HCV patients with less ideal and more advanced Hep C and other conditions. Then other genotypes etc. It could be a couple of years or longer before possible FDA approval if it works.
Avatar universal
Thank you for your explanation.

My guess is that anyone with moderate or severe fibrous, cirrhosis or elevated chance of progression from F0/F1 shouldn't consider waiting for a couple of years to see if this tx gets approved.   They should try to get tx with these new now approved and/or recommended off label drugs depending on their doctor's advice.

If TT-034 or similar one shot(or pills) tx is successful with few serious side effects it may be the way to go in a couple of years.   Even if it was priced at $10,000 a shot or ? tx it's much lower than Sovaldi   Opinion Gilead is trying to get as much as it can for Sovaldi now because of future competition that will dramatically lower the price in the next year or two.  Even now I bet their average price is much lower than $1,000 pp if you include discounts to major health organizations, copay assistance and free drug no ins low income.  .
142526 tn?1397090672
How it works:  

This is a first-time use of a method of therapy designed to transfer anti-HCV genetic sequences into the hepatocytes of subjects infected with HCV. The anti-HCV sequences will be comprised of three different short hairpin RNAs (shRNA) that have the ability to directly cleave the RNA genome of HCV by a process known as RNA interference. The transfer of the anti-HCV sequences will be accomplished using a "vector" that was made from an adenovirus-associated virus (AAV) by removing the viral genes and replacing them with a non-replicating genetic sequence that produces three different shRNA that target three different regions within the HCV genes.

Works differently from any other tx's.
Avatar universal
However, the shra  "medicine" continues to be produced in the cytoplasm of liver cells by the cells own "machinery". It is one shot with long lasting viral fighting effects.
1689583 tn?1387752394
You are all so smart.... I don't have a clue what anyone of you have said.
Avatar universal
Simply it's using Immunotherapy to kill the virus. Basically it's creating an environment in which your own immune system destroys the enemy (virus)

They are using it also in the treatment of cancer with promising results. No doubt within the next 5 years many diseases will be treated without drugs that kill both healthy cells and toxic cells such as chemotherapy.  Immunotherapy boosts our own immune system to attack damaged cells only.

It's extremely exciting days ahead for the medical community, and those of us that have chronic diseases.
We will soon see the face of medicine change in a big way!
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