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4.2.0 Other Therapies

4.2.0 Other Therapies

4.2.1 Taribavirin (Viramidine)

Viramidine (VRD) is a pro-drug of ribavirin produced by Valeant Pharmaceuticals. A prodrug is a drug that is concentrated in a certain organ such as the liver rather than distributed throughout the entire blood system. The body has to change it to an active form before the full effect can be seen. Studies seem to indicate that viramidine is safer, but less effective than ribavirin.

Since Viramidine directly targets the liver, it is supposed that it won’t cause anemia so easily. Valeant reported results from its Phase III study called VISER2, comparing Viramidine (600 mg twice a day) to ribavirin (weight-based 1000/1200 mg twice a day) combined with peg-IFN alpha 2a. The study, enrolling 962 HCV+ naïve patients, lasted 24 weeks for genotype 2 or 3, and 48 weeks for non-genotype 2, 3 patients. Information about results according to genotype, weight and viral load has not yet been released. Treatment with Viramidine resulted in lower anemia than in the patients treated in the ribavirin group (6% compared to 22). SVR rates were 40% for the Viramidine arm compared to 55% for the ribavirin arm, but it was found that higher amounts of Viramidine in the blood resulted in a higher SVR, without higher rates of anemia.
(www.hcvadvocate.org September 12, 2006)

The Phase III ViSER study enrolled 972 treatment-naïve patients, who were treated with peg-IFN alpha-2b and either a fixed-dose VRD (600 mg BID) or weight-based RBV (1000 or 1200 mg/day). SVR rates were 37.7% with VRD and 52.3% with RBV. The study failed to prove it was equally effective as RBV, but incidence of anemia was about four times lower with VRD than with RBV. These results suggest fixed-dose VRD given 600 mg BID is not a large enough dose to treat patients with chronic hepatitis C, so a weight-based trial is currently under way.
(www.ncbi.nlm.nih.gov/pubmed/19585653 2009)

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4.2.2 Zadaxin (Thymosin)

Researchers believe that Zadaxin, SciClone’s thymosin alpha-1, a synthetic polypeptide, works by boosting
the ability of the body's immune system to produce T cells.

In November 1996, results from a Phase III study in chronic hepatitis C patients receiving a combination therapy of thymosin alpha 1 and interferon alpha-2B showed almost 50% of the 65 patients had complete normalization of ALT in the thymosin combination treated group and in less than 20% of the interferon-only treated group. Also observed were significant early virologic responses in patients treated with combination therapy when compared to the interferon-alone arm.

In a U.S. hepatitis C trial, 41.9% of those treated with Zadaxin combined with interferon responded while only 16.6% patients responded when treated with interferon alone, according to the SciClone website.

When used in combination with IFN, fever, fatigue, muscle aches, nausea, vomiting, and neutropenia were reported at a significantly higher rate than with IFN alpha 2b alone or with placebo Hepatology 1998; 27:1128-35).

Zadaxin is not yet approved in Canada, although it is now available in the US and Europe and many other countries, including Mexico.

Results from a Phase III trial for non-responders, who completed 48 weeks of triple therapy combining Pegasys with Zadaxin, showed an SVR in 6 out of the 30 patients (20%) at week 72. 26 of the patients were infected with genotype 1, and their SVR rate was 23% (6 out of 26 patients).

SciClone and its European partner Sigma-Tau completed enrolment for a Phase III clinical trial evaluating Zadaxin combined with peg-IFN alpha and ribavirin in 553 HCV+ patients in Europe. "We believe that ZADAXIN could increase the therapeutic efficacy of standard HCV treatment without additional side effects, particularly for non-responder HCV patients infected with a high viral load of the genotype 1 strain of the virus," Data are expected to be announced by the end of 2008.
(www.hcvadvocate.org/hepatitis/hepC/HCVDrugs2007.pdf December 28, 2006)

In June 2007, SciClone initiated a Phase II clinical trial using its compound SCV-07, an immune stimulator, as monotherapy to treat patients infected with HCV. SciClone plans to report data in the first quarter of 2008.

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4.2.3 Amantadine

Younossi ZM, et al. (Dig Dis Sci. 2005 May;50(5):970-5) say “The addition of amantadine to pegylated interferon alpha-2b and ribavirin does not seem to increase the efficicacy of this regimen.”In this study, 400 naïve patients were treated with IFN + ribavirin, and with amantadine or a placebo. “SVR was observed in 52% of the amantadine group and in 43.5% of the control group (P = .11). Among patients with HCV genotype 1 infection, the corresponding SVR rates were 39% and 31%, respectively.”(T Berg et al. Triple therapy with amantadine in treatment-naïve patients with chronic hepatitis C:Hepatology 37 (6):1359-1367. June 2003).

If amantadine works it probably involves immune mediation, inducing the production of interleukins and may be best used combined with interferon and ribavirin to produce a synergistic effect. More research is needed. (J. K. Lim, et al, J Viral Hepatitis Sept 2005)

Egyptian researchers, looking for an effective and inexpensive treatment for HCV patients, enrolled 170 naïve patients with elevated ALT in a study.

Group I were given a daily combination of ribavirin (600-800 mg) plus amantadine (200 mg) and ursodeoxycholic acid (UDCA) (500 mg) for 24 weeks.

Group II were given milk thistle 450 mg/day for 24 weeks.

Results based on the remaining patients after 16 dropped out: ALT was normal in 58.5% and 15.3%, respectively, and end of treatment virological response (ETVR) was achieved in 2.4% and 0% of Groups I and II, respectively.

Twenty-four weeks after the end of therapy, sustained biochemical response (SBR) was retained in 28% and 2.8%, and SVR was maintained in 2.4% and 0%. Biopsies showed improvement in group I patients (PMID: 15998425). It looks like ALT levels might decline, but viral loads probably do not.
(www.journals.uchicago.edu/cgi-bin/resolve?id=doi:10.1086/319220&erFrom=5516982323875455201Guest and
www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1492374 June 2004 )

Two studies published in 2006 produced conflicting results: In the February 2006 Journal of Hepatology, results of a trial in 200 treatment-naive chronic genotype 1 patients taking standard treatment plus amantadine showed no improvement in viral load reduction or in quality of life over standard treatment alone. However, in another 200-person study by Marianne Maynard, et al, published on the Journal of Hepatology website, non-responders who received standard treatment plus amantadine were more likely to achieve SVR than those taking standard treatment alone. The response rates were 24% and 16%, respectively. (www.hcvadvocate.org/news/newsRev/2006/HJR-3.3.html#3)

Clinical trials of amantadine for hepatitis C infection have been cancelled.
(http://hcvadvocate.org/hepatitis/hepC/HCVDrugs.html#Cancelled Nov 2007)

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4.2.4 Alinia (Annita, Nitazoxanide)

Romark’s nitazoxanide, called Alinia, is a thiazolide. It inhibits synthesis of structural proteins of the virus. Alinia is already under development in the US for treating some gastrointestinal problems (parasites, Crohn’s, etc.) (/PRNewswire/ Jan 10, 2006, Romark to Develop Alinia(R) (nitazoxanide) as New Treatment for Chronic Hepatitis C) Studies have shown it to be an effective inhibitor of HCV and it doesn’t cause resistant mutations. It works synergistically with IFN and DDA’s (Direct-Acting Antivirals) without adding toxicity. It may be able to replace ribavirin in GT4 patients. It is being studied in HCV/HIV co-infected patients.

On April 15, 2010, Romark announced results from its STEALTH C-3 Phase II clinical trial, a clinical study of Alinia (nitazoxanide) in treatment-naive GT1 patients. The results were presented at 2010 EASL Conference in Vienna. 35% of the patients had fibrosis stage 3 or 4. 44% of patients treated with Alinia/Pegasys/Copegus achieved SVR12 (SVR 12 weeks after the end of treatment) vs. 32% of those taking only Pegasys/Copegus. Strangely, the higher the baseline viral load, the higher the SVR12 rates.

Final results were due in May 2010. This was the first trial of Alinia in treatment-naïve genotype 1 patients. Phase III trials were to begin later in 2010, using 675 mg controlled-release tablets with pegIFN with or without RBV. Other trials are already using the controlled-release tablets in GT1 and 4 patients. Some of the arms were to last only 24 weeks, and some don’t include RBV. Important recent studies have included one arm that combined Alinia with pegIFN/RBV in GT1 non-responders. Data for this trial was released on April 17, 2011.

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4.2.5 Celgosivir (MX-3253)

MX-3253 (celgosivir), an oral alpha-glucosidase I inhibitor by Micrologix is a derivative of the Australian Black Bean chestnut tree. It inhibits an enzyme that affects the processing of glyoproteins which HCV requires to live. The product has an advantage of inhibiting an enzyme rather than a virus, thus avoiding resistant mutations.

The Phase II trial, conducted in Vancouver, BC, and in San Diego, studied 57 genotype 1 non-responders, divided into 3 arms 1) celgosivir, peg-IFN alpha-2b, and ribavirin [“triple”]; 2) celgosivir plus peg-IFN [“double”]; or 3) placebo, peg-IFN plus ribavirin [“control”]. The treatment took place over 12 weeks. The therapy was well tolerated, and there were no adverse effects. Only 7 patients dropped out. The results showed 42% EVR (Early Viral Response) with the celgosivir triple combination arm, and 10% EVR in the control treatment arm. This triple combination gave a 90% viral load reduction in 66% of the patients at the end of the 12 week trial. These new results complete the retesting required by Migenix’s partner Merck last February of half of the original viral load samples.

The drug has demonstrated synergy with other HCV treatments and other drugs in development for the treatment of HCV (e.g., polymerase inhibitors), but Schering/Merck decided it wouldn’t renew its agreement of exclusivity with Migenix for celgosivir, but might help with study design and drug supplies. That leaves Migenix free to discuss partnerships with other interested parties.
(www.hcvadvocate.org/news/reports/EASL2007/EASL07-1.htm#NewClinicalStudy and
http://tsedb.globeinvestor.com/servlet/WireFeedRedirect?cf=GlobeInvestor/tsx/config&date=20070627&arc hive=prnews&slug=TO434 June 27, 2007)

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4.2.6 HCV Monoclonal Antibodies (mAb’s)

Civacir - Human antibodies to HCV, produced using XTL’s Trimera mouse system (a mouse genetically altered to carry human tissues for in vivo [in a living organism] experiments) have now been used to develop a product called Civacir. Nabi’s Civacir is a polyclonal antibody to hepatitis C, developed from antibodies taken from screened HCV+ donors and purified. These antibodies neutralize the hepatitis C virus. The product is being developed to prevent re-infection in transplant patients. Civacir was granted fast track status by the US FDA in 2006. Nabi has partnered with Kedrion, a biopharmaceutical company in Italy, to sell Civacir in Europe as well as in the US.

In January 2007, a randomized Phase II clinical trial began, treating 20 patients with Civacir vs. 10 patients treated with standard treatment. The data collected will be fibrosis scores, HCV levels, liver enzyme levels, safety and tolerance. Results are expected in the second half of 2008.
(www.nabi.com/pipeline/pipeline.php?id=4 )

Nabi Biopharmaceuticals initiated another Phase II clinical trial for Civacir—a proof-of-concept trial. The developers plan to use it to prevent the recurrence of HCV in liver transplants, or to prevent infection in transplant patients who received a liver infected with HCV. The product is being developed with Kedrion,. It is hoped that post-transplant patients can be treated with Civacir sooner after transplant surgery than with other drugs.
(www.prnewswire.com/news-releases/nabi-biopharmaceuticals-announces-initiation-of-civacirr-phase-ii-proof-of--concept-clinical-trial-53513912.html Jan. 16, 2011)

Bavituximab (formerly Tarvacin) produced by Peregrine is the first of anti-phosphotidylserine (anti-PS) monoclonal antibodies that bind to normal parts of a cell that become exposed when infected with a virus, and to the surface of enveloped viruses. These antibodies may stimulate the immune system to destroy both the virus particles and the infected cells.
(http://money.cnn.com/news/newsfeeds/articles/prnewswire/LATU12707082007-1.htm August 07, 2007)

Data from a Phase Ib study was presented at the 2007 AASLD Meeting. Twenty-four patients enrolled in the study were divided into 6 dosing groups. Eleven were non-responders, 8 were relapsers and 5 were treatment-naïve. 15 were genotype 1, 8 were genotype 3 and 1 was genotype 2. They were given 90 minutes of the drug IV twice a week for 2 weeks, at different doses, then followed for 12 weeks. Infusions up to 6 mg/kg were safe and well-tolerated. No serious adverse events or early discontinuations were reported. Two weeks of dosing shows antiviral effect in some patients. (Jules Levin www.natap.org )

Peregrine has finished enrolling 66 genotype 1 treatment-naïve patients for its second Phase II trial of Bavituximab. Participants will be treated for 12 weeks with Bavituximab or interferon plus ribavirin. Early Virologic Response (EVR= > 2 log reduction at 12 weeks) results are expected by the end of 2011 or early in 2012. The drug has been shown to be safe in 3 previous Phase I HCV studies. The drug is also being tested in patients with pancreatic and lung cancer.

CT-1011 - CureTech and Teva will collaborate on a Phase I/II trial of the monoclonal antibody CT-1011 around the end of 2009. The trial will enrol 20 patients. CureTech is also studying the drug in a Phase II trial for liver and bowel cancer.
(www.israel21c.org/index.php?option=comcontent&view=article&id=7123:curetech-to-begin-hepatitis-vaccine-trial&catid=62:briefs&Itemid=141 August 18, 2009)

MBL-HCV1 - Researchers at MassBiologics, part of the University of Massachusetts Medical School, began a Phase I clinical trial on July 28, 2009, testing their hepatitis C neutralizing vaccine, MBL-HCV1, a human monoclonal antibody that neutralizes HCV. The trial administers MBL-HCV1 to 30 healthy subjects and should be finished by the end of the year. It is hoped that the drug will be used as a therapy before and during transplant surgery, to remove any remaining virus and prevent infection of the new liver. Few side effects are anticipated. It may be used combined with other new drugs to treat newly-diagnosed Hep C patients, as well.
(www.huliq.com/11/84595/new-antibody-targets-hepatitis-c-virus )

The company began enrolling patients in a Phase II trial of MBL-HCV1 in December 2010. Their intention is to prevent re-infection in liver transplant patients. They hope to enrol 16 patients in the first part of the study. The disease progresses more rapidly in the new liver, developing cirrhosis in 5 years in 20% of the recipients. Current treatment is not well-tolerated in transplant patients. In this Phase II study, patients will receive the drug or a placebo 1 to 4 hours before surgery, right before the new liver is transplanted, after surgery, once daily for the first week after the transplant surgery, and once more 14 days after surgery. This is an effort to remove the virus from the patient’s bloodstream so it can’t infect the new liver.
(www.eatg.org/eatg/Global-HIV-News/Hepatitis/MBL-HCV1-Phase-2-trial-begins-to-prevent-hepatitis-C-virus-infection-in-liver-transplant-patients 19/01/2011)

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4.2.7 Toll-like Receptor Agonists IMO-2125, ANA773, and SD-101

Idera has begun a Phase I trial with IMO-2125, a Toll-like Receptor (TLR) 9 agonist designed to make the body produce its own interferon and other immune responses against HCV. When tested in primates, IMO-2125 proved effective at producing cytokines that inhibit replication of HCV. This trial is planned for 40 non-responders, in 4 arms of different doses. Eight of them will receive a placebo. The trial consists of one injection weekly for 4 weeks.
(www.iderapharma.com/file/News%2020070917.pdf Oct 4, 2007)

Anadys’ ANA773 is an oral drug that induces interferons and acts through the toll-like receptor 7 (TLR7) pathway. On August 11, 2009, the company announced data for the final group of patients that took part in the Phase I clinical trial, a 10-day study of the drug as monotherapy, conducted in the Netherlands.

Subjects who took 2000 mg of ANA773 every 2 days for 10 days had an average of 1.3 log drop in viral load, while those receiving placebo had an average decline of 0.3 log drop. The drug was well tolerated, with no reports of serious side effects. The company planned to investigate the combination of the drug with ribavirin and investigate other dosing schedules. Complete results were to be released at the AASLD conference Oct. 30-Nov. 3 in Boston in 2010 (Anadys Pharmaceuticals, Inc via NATAP)

More recently the company presented data from a Phase I cancer study of ANA773 at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on June 4, 2011. In that study, the product was shown to be safe at a dose that produced the desired effects on the immune system, with a partial response in a cancer patient. Anadys is preparing for a European Phase IIa study combining ANA773 with ribavirin in HCV patients and hopes to have 28-day data from the Phase IIa HCV study near the end of 2011.
(http://hepatitiscnewdrugs.blogspot.com/2011/05/anadys-highlights-ana773-data-to-be.html May 25, 2011)

Anadys Pharmaceuticals has just been acquired by Roche.
(www.roche.com/media/mediareleases/med-cor-2011-10-17.htm Oct 17, 2011)

Dynavax Technologies has developed SD-101, an oligonucleotide called a TLR-9 agonist, which is made to boost the body’s immune response to HCV by affecting the T-cell and natural killer cells by way of the toll-like receptor 9 (TLR-9) and encouraging our bodies to make more interferon-alpha.

In this Phase 1b trial, 34 treatment-naïve genotype 1 (GT1) patients were injected once a week for 4 weeks, with doses of SD-101 ranging from 0.1 mg to 5.0 mg or placebo to see how safe and effective the drug is. There were few side effects, usually mild flu-like symptoms and irritated injection sites. SD-101 produced a drop in viral load after only one dose of SD-101 given as mono-therapy. The fast drop of HCV RNA indicate that more trials should be done.

In this Phase 1b trial, 34 treatment-naïve genotype 1 patients were injected once a week with doses of SD-101 ranging from 0.1 mg. to 5.0 mg. or placebo to see how safe and effective the drug is. There were few side effects, usually mild flu-like symptoms and irritated injection sites. SD-101 produced a drop in viral load after only one dose of SD-101 given as mono-therapy. The fast drop of HCV RNA indicate that more trials should be done.

Antipodean Pharmaceuticals’ MitoQ is a super antioxidant that binds with coenzyme Q10, causing it to accumulate 700 times more intensely than co-Q10 alone inside the mitochondria. The mitochondria produces energy within the cell, and MitoQ protects the cell from oxidation damage and appears to be more powerful than common antioxidants. Oxidation in liver cells can be very dangerous to those with liver disease so some clinical trials have been done. Researchers in Alabama studied the effect of MitoQ on fatty liver in animals, whose livers were damaged with alcohol for the study. MitoQ was able to neutralize free radicals before they could hurt the mitochondria, preventing the effects that cause fatty liver.
(www.hepatitis-central.com/mt/archives/2011/11/ and
http://onlinelibrary.wiley.com/doi/10.1002/hep.24377/abstract 24 Jun 2011)

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4.2.8 Interferon Alpha Gene Therapy

Interferon Alpha Gene Therapy is a treatment for hepatitis C that delivers genes for IFN alpha-2b specifically
to liver cells, hopefully making the treatment more effective.
In a laboratory trial HCV completely disappeared, suggesting that IFN-alpha produced by gene transfer effectively inhibits HCV replication in liver cells. This study supports the development of IFN-alpha gene therapy for HCV-associated liver diseases (Biochem Biophys Res Commun. 2003 Aug 8;307(4):814-9).
In an Egyptian study in rats, IFN-alpha gene transfer was studied to see if it would protect them from damage from known toxins, and was found to be effective in preventing liver fibrosis and cancer. “IFN-alpha gene therapy may be justified in clinical trials for high-risk candidates with hepatic carcinogenesis.”

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4.2.9 Oglufanide

Physicians at Southern Health have started a Phase IIa clinical trial with Implicit Bioscience's drug, oglufanide disodium, a regulator of the body's immune response, is being given to patients with chronic Hep C. It was originally used to treat severe infectious disease in Russia, and was studied in cancer clinical trials in the US. It was acquired by Implicit Bioscience in 2005. The Phase IIa trial of intranasal oglufanide disodium will complement the ongoing Phase Ib study of subcutaneously administered drug in Brisbane’s Princess Alexandra Hospital.
(www.medicalnewstoday.com/articles/80603.php Aug 25, 2007)
2008, and it is hoped that Phase II studies will follow.
(www.medicalnewstoday.com/articles/72827.php 31 May 2007 and

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4.2.10 NOV-205

A Phase Ib of Novelo’s NOV-205 monotherapy in 30 Genotype 1 non-responders to test the drug compared to a placebo, looking for early viral response of more than a 0.5 log10 drop in viral loads and improvement in ALT and AST. Patients will be observed after single and multiple applications of the drug. NOV-205 is already approved and used for liver disease in Russia, where clinical trials showed improved blood tests for hepatitis C and for liver damage.
(www.clinicaltrials.gov/ct/show/NCT00372983?order=3 August 2006)

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4.2.11 JKB-122

Jenken Biosciences’ JKB-122, an antifibrotic, was cleared by the US FDA for Phase II clinical trials to see if it can restore liver function in around 150 HCV+ non-responders, over a period of 3 months, either alone or combined with standard treatment. The trial was scheduled to start at the beginning of 2007, and should take 1 to 2 years to complete. The drug has been in previous trials with alcoholic patients, where it reduced inflammation and normalized liver enzymes.

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4.2.12 CB5300

Canopus BioPharma’s CB5300, one of the company’s flavivirus inhibitors, will be tested in a clinical trial since its in-vitro trial proved successful in bovine viral diarrhea, also a flavivirus, like HCV. The CB5300 have already been FDA-approved and found to be generally safe, and patents for this and other antivirals are pending. This Phase II trial in humans will take place in the US and Australia.
(http://markets.chron.com/chron?GUID=3653679&Page=MediaViewer&Ticker=CBIA Oct 31, 2007)

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4.2.13 MitoQ

Antipodean Pharmaceuticals’ MitoQ(R) is an antioxidant that selectively blocks mitochondrial damage and prevents aptosis (programmed cell death). Antioxidants can reduce liver damage by HCV which can cause fatty liver, progressing to fibrosis or cirrhosis. In a Phase II trial with 30 HCV+ patients, ALTs were measured before treatment with MitoQ. Treatment lasted 28 days. Patients received either MtioQ 40 mg/day, MitoQ 80 mg/day, or a placebo. There was a 26.4% decrease in ALTs in group 1, 28% in group 2, suggesting that MitoQ may stop progression of liver disease. The drug showed no safety problems.

MitoQ binds with coenzyme Q10, causing it to accumulate 700 times more intensely than co-Q10 alone, inside the mitochondria. The mitochondria produces energy within the cell, and MitoQ, which has a special tendency to gather in the mitochondria, protects the cell from oxidation damage and appears to be more powerful than common antioxidants. Researchers in Alabama studied the effect of MitoQ on fatty liver in animals, whose livers were damaged with alcohol. MitoQ was able to neutralize free radicals before they could hurt the mitochondria, preventing the effects that cause fatty liver.
(www.hepatitis-central.com/mt/archives/2011/11/ and the April 2011 edition of the journal Hepatology

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4.2.14 CTS-1027

Conatus Pharmaceuticals’ CTS-1027, an oral, small molecule, matrix metalloproteinase (MMP) inhibitor, reduced liver damage, reduced ALTs and improved survival and liver histology in a recent Phase I trial. Too much MMP activity can cause the architecture of the liver to become deformed and cause inflammation.
(www.medicalnewstoday.com/articles/87771.php 06 Nov 2007 and
http://clinicaltrials.gov/ct2/show/NCT00570336?spons=%22FGK+Clinical+Research+GmbH%22&sponsex= Y&rank=3)

CTS-1027 is thought to assist the immune system’s clearance of the cells infected with the virus. CTS-1027 was given to 67 G1 null-responders (no response at all to previous therapy), the most difficult of all to treat. These patients were tested for the CT and TT allelic variants of the IL28B gene, which predict non-response, and 95% possessed them. Even so, interim results from week 24 showed 34% undetectable at week 24. (EASL 2011)

The Phase II trial of CTS-1027 has been terminated due to worrisome side effects and abnormal lab results in some patients. The data is under review.

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4.2.15 Interleukins

Early laboratory trials showed that some interleukins might be able to suppress the hepatitis C virus, although more recent studies have shown they are not very effective. Even so, scientists continue trying to develop interleukin compounds against hepatitis C.

A study of 5 microg/kg of rhIL-11(Neumega) injected daily for 12 weeks showed improved biopsy results in 11 of the 20 subjects enrolled. The treatment seemed to cause a decrease in ALT levels from an average of 113 IU/L to 65 IU/L at week 12; however, viral load was not affected. Platelets increased, too. The study results suggest that rhIL-11 may be good for patients with liver inflammation and advanced liver disease from chronic HCV. (Am J Gastroenterol. 2004 Dec;99 (12):2359-64.)

Cytheris will start a Phase I clinical trial of its CYT107 recombinant interleukin, injected once a week, four times, along with standard treatment, in non-responders to previous therapy. It is hoped that the drug will restore T cell function.

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4.2.16 UDCA (ursodeoxycholic acid)

There is no proven therapy for fatty liver. This trial gave 30 mg per kg of weight each day of UDCA (ursodeoxycholic acid) or placebo to 126 patients with non-alcoholic steatosis, (NASH or fatty liver) and ALT levels over 50 IU/L to see if it was safe. The treatment lasted 12 months. The goal was a lower ALT, indicating less inflammation. ALT decreased an average of 55% with UDCA, and 35% with placebo. Average AST and GST decreased 59% with UDCA, and increased with placebo.

The UDCA group reported more diarrhea, pain in the abdomen, and gastrointestinal problems than the non-UDCA group, but also reported improvement in strength and less right upper quadrant pain. (EASL Conference 2009)

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4.2.17 Rosiglitazone

Previous short trials of glitazones had controversial biopsy results. Researchers hoped for better results with longer treatment, and re-enrolled 53 patients who had completed the FLIRT trial, which was 1 year of Rosiglitazone (RSG) or placebo. They were enrolled in two more years of treatment, all with RSG.

40 finished and were biopsied for a 3rd time. In the placebo/RSG group, steatosis (fatty liver) decreased by an average of 15% and in the RSG/RSG group, there was a 20% reduction of steatosis only in the first year. Fibrosis did not change. Researchers concluded that RSG has a good effect on steatosis during the first year, but no benefit after that, other than maintaining a good effect on insulin and liver enzyme levels. (EASL 2009)

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4.2.18 CF102

A Phase I clinical trial of Can-Fite’s CF102 found the drug to be safe in 25 healthy adults. The Phase I/II trial began in July 2009, and plans to enroll 32 genotype 1 subjects, treating them with oral CF102 twice a day for 2 weeks. The trial is expected to be completed in June 2010. A separate study is taking place for the product as a liver cancer treatment. This drug binds to the adenosine 3 receptor (A3R), which is found on cancer and inflammatory cells, promoting apoptosis (programmed cell death).

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4.2.19 SCY-635

Scynexis’ SCY-635 is the first candidate in a new class of non-immunosuppressive cyclophilin inhibitors. Probably the most famous of the cyclophilin inhibitors is Cyclosporine A, used for decades for anti-rejection of transplanted organs. SCY-635 lets the immune system detect the virus. It reactivates the body’s natural defences so that it can stop the HCV from replicating, raising hopes that it may be a good replacement for the interferons used in SOC (pegIFN/RBV), with fewer side effects.

Results from the Phase Ib monotherapy trial in 56 genotype 1 patients were presented at the EASL 2009 Conference. The study lasted 15 days, and the drug (given orally) was well tolerated. The highest dose (900 mg/day) showed important antiviral activity, with an average viral load drop of 2.2 log on the last day of treatment. The maximum drop occurred on the 15th day, suggesting that longer treatment may be more effective. A Phase II study was planned for the second half of 2009.
(www.scynexis.com, http://au.sys-con.com, http://www.hcvadvocate.org May 5, 2009)

Scynexis presented data at the AASLD 2011 in San Francisco. SCY-635 is currently in Phase II studies. In earlier studies the drug was well-tolerated and showed antiviral activity. It interacted well with other approved drugs in vitro, and may be an important addition to any new SOC.

It may be less likely to produce resistant strains than the DAAs (direct-acting antivirals). SCY-635 monotherapy showed increased concentrations of interferons like IFN alpha and lambda-1 in GT1a patients.

Two other studies were also presented. One showed a correlation of SCY-635 levels and the presence of type 1 and type 3 interferons in vitro, and that SCY-635 is as effective as IFNα-2b in clearing the virus and preventing rebound in vitro.

The other studied drug interactions between SCY-635 and telaprevir and showed that SCY-635 was less likely to produce adverse drug interactions compared in vitro to other cyclophilin inhibitors.
(www.scynexis.com/scy-635-restores-the-bodys-innate-immune-response-to-hcv/ Nov 7, 2011)

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4.2.20 Fluvastatin

Fluvastin is a drug that is already approved for lowering cholesterol by inhibiting a liver enzyme, HMG Co-A reductase. The drug is expected to prevent serious fibrosis.

This study treated 209 treatment-naïve G1b patients with fluvastatin or placebo plus SOC for 48 weeks. Fluvastatin was given for a total of 72 weeks, no matter the patient’s lipid levels.

The results showed that SVR was 74.39% in the fluvastatin combo, vs. 58.44% from SOC. And fluvastatin is affordable! (EASL 2011)

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4.1.5g IDX184 + IDX375

Hepatitis C FAQ

4.3.0 Vaccines