Bavituximab ;Peregrine Completes Enrollment in Phase Ib HCV/HIV Coinfection Trial

Peregrine Pharmaceuticals IncPPHM 1/31/2011 8:01:27 AMClinical Data From Targeted Antibody Bavituximab Expected in 2Q11

TUSTIN, CA, Jan 31, 2011 (MARKETWIRE via COMTEX News Network) --
Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment of cancer and viral infections, today announced the completion of enrollment in the company's Phase Ib dose escalation safety study of bavituximab in patients coinfected with chronic hepatitis C virus (HCV) and HIV. Previously this month, Peregrine initiated a randomized Phase II HCV trial to evaluate 12 weeks of therapy with bavituximab, a phosphatidylserine (PS)-targeting monoclonal antibody with immune-modulating potential, in combination with the antiviral drug ribavirin versus standard of care, pegylated interferon alpha 2a and ribavirin.

"Completion of enrollment in our third Phase I HCV trial is an important milestone for our bavituximab antiviral program, and sets the stage for reporting clinical data at a medical conference in the second quarter of this year while we begin to evaluate combination treatment with the antiviral agent ribavirin in a recently initiated study," said Steven W. King, president and chief executive officer of Peregrine. "Though standard treatment for chronic HCV may soon evolve with the introduction of new targeted antiviral drug candidates, immune stimulation with interferon remains a critical component of therapy. Preclinical data support the potential combination of bavituximab and ribavirin and we look forward to seeing how this combination initially compares to standard interferon and ribavirin treatment for 12 weeks in our Phase II study for patients infected with HCV."

In prior HCV clinical trials, bavituximab administered as monotherapy in single and multiple doses demonstrated a positive safety profile with no dose-limiting toxicities or serious adverse events. Bavituximab as a monotherapy also showed promising on therapy antiviral activity of up to 1.5 log viral load reduction.

Bavituximab may address a fundamental "immune evasion" mechanism exploited by many infectious pathogens. A growing body of published data from researchers worldwide shows that bavituximab's PS target, exposed on the surface of cells infected by viruses and protozoan parasites, suppresses the immune system's ability to fight disease. PS-targeting antibodies such as bavituximab bind to PS and block the immunosuppressive signals created by the target, thereby allowing the immune system to mount a robust immune response against the pathogen.

About the Phase Ib HCV Trial Peregrine's open-label, dose escalation safety study is designed to assess the safety and of bavituximab in up to 24 patients chronically infected with HCV and HIV. Patient cohorts received ascending dose levels of bavituximab weekly for up to 8 weeks. Primary endpoints include safety and pharmacokinetics, and secondary endpoints will measure HCV and HIV RNA by PCR. For further information about Peregrine's HCV trials, please visit www.peregrinetrials.com or http://www.clinicaltrials.gov/ct2/results?term=bavituximab.

About HCV According to the U.S. Centers for Disease Control and Prevention, an estimated 3.2 million individuals in the United States have chronic hepatitis C virus (HCV) infection. Chronic HCV infection is a serious disease that can result in long-term health problems, including liver damage, liver failure, liver cancer, or death. It is the leading cause of cirrhosis and liver cancer and the most common reason for liver transplant in the United States. Approximately 8,000 to 10,000 people die every year from HCV-related liver disease.

About Bavituximab's Antiviral Approach Bavituximab is the first in a new class of patented antibody therapeutics that target and bind to phosphatidylserine (PS), a specific phospholipid component of cell membranes. Bavituximab helps reactivate and direct the body's immune system to destroy infected cells and virus particles that exhibit this specific phospholipid on their surface. Since their target is host-derived rather than pathogen-derived, PS-targeting antibodies have the potential for broad-spectrum antiviral activity and are also expected to be much less susceptible to the viral mutations that often lead to drug resistance.

Researchers have found that PS is exposed on the outer membrane of cells infected with HCV, HIV, influenza, herpes viruses, hemorrhagic fever viruses, respiratory syncytial virus, measles as well as other viruses. A growing body of scientific publications, including Nature Medicine and The Journal of Experimental Medicine, has highlighted data on the role of PS and Peregrine's PS-targeting therapies in infectious diseases.

About Peregrine Pharmaceuticals Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials for the treatment of cancer and serious viral infections. The company is pursuing multiple clinical programs in cancer and hepatitis C virus infection with its lead product candidate bavituximab and novel brain cancer agent Cotara(R). Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. (www.avidbio.com), which provides development and biomanufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at www.peregrineinc.com.

Safe Harbor Statement: Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceuticals' intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements involve risks and uncertainties including, but not limited to, the risk that results from the Phase Ib or Phase II HCV trials will not be consistent with results experienced in earlier HCV clinical trials and preclinical studies, the risk that investigators may experience delays in patient enrollment, risk that results may not support registration filings with the U.S. Food and Drug Administration, and the risk that Peregrine may not have or raise adequate financial resources to complete the planned clinical programs. Factors that could cause actual results to differ materially or otherwise adversely impact the company's ability to obtain regulatory approval for its product candidates include, but are not limited to, uncertainties associated with completing preclinical and clinical trials for our technologies; the early stage of product development; the significant costs to develop our products as all of our products are currently in development, preclinical studies or clinical trials; obtaining additional financing to support our operations and the development of our products; obtaining regulatory approval for our technologies; anticipated timing of regulatory filings and the potential success in gaining regulatory approval and complying with governmental regulations applicable to our business. Our business could be affected by a number of other factors, including the risk factors listed from time to time in the company's SEC reports including, but not limited to, the annual report on Form 10-K for the year ended April 30, 2010 and the quarterly report on Form 10-Q for the quarter ended October 31, 2010. The company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. Peregrine Pharmaceuticals, Inc. disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release.

Peregrine Contact: Amy Figueroa Peregrine Pharmaceuticals (800) 987-8256 info@peregrineinc.com

SOURCE: Peregrine Pharmaceuticals

mailto:info@peregrineinc.com

Copyright 2011 Marketwire, Inc., All rights reserved.

"Nuclear Sludge" Candies Recalled for High Lead Content

Recall -- Firm Press Release

FDA posts press releases and other notices of recalls and market withdrawals from the firms involved as a service to consumers, the media, and other interested parties. FDA does not endorse either the product or the company.

Candy Dynamics Expands Recall To All Toxic Waste® Brand Nuclear Sludge®
Products All Flavors And All Sizes

Contact:
Laura King
888-400-7606

FOR IMMEDIATE RELEASE - January 27, 2010 - Circle City Marketing and Distributing, doing business as Candy Dynamics, Indianapolis, IN, is issuing a voluntary recall of all Toxic Waste® brand Nuclear Sludge® products, all flavors, 0.3 oz (8 g) size pieces. The product is imported from Pakistan.

On January 13, 2011, the company previously recalled Toxic Waste Brand® Nuclear Sludge®, Net wt. 0.7 oz (20g) size, all flavors. With this recall of the smaller piece size, the company has now recalled all products labeled as "Nuclear Sludge®".

Further testing by the company indicates that while some of the smaller sized products were below the FDA limit, some contain elevated levels of lead (0.101 parts per million to .311 ppm; the U.S. FDA tolerance is 0.1 ppm) that potentially could cause health problems, particularly for infants, small children, and pregnant women.

The company has determined to recall all lots and all flavors of the smaller sized product distributed from the product's inception in May 2009 through January 2011.

The smaller sized products are identified as: Toxic Waste® Nuclear Sludge® Cherry (UPC 0 89894 81901 1), Toxic Waste® Nuclear Sludge® Green Apple (UPC 0 89894 81701 7), and Toxic Waste® Nuclear Sludge® Blue Raspberry (UPC 0 89894 81801 4). Each individual piece has a net wt. of 0.3 oz (8 g) and were sold individually, as part of a 'Party Bag’ or Membership kit, and packed in 30 ct., 80 ct., and 120 ct. bags and a 120 ct. fishbowl.

No other "Toxic Waste®" brand product, besides those labeled "Nuclear Sludge®" is affected by this recall.

No illnesses have been reported to date in connection with this problem.

The recalled Nuclear Sludge® products were distributed nationwide in retail stores and through mail orders. The product was also distributed in Canada and in very limited quantities in Guatemala, Ireland, Jordan, Korea, Mexico and El Salvador.

The company is discontinuing the sale of Nuclear Sludge® products in the U.S.

Candy Dynamics is sending recall notices to its direct customers. Anyone in possession of the recalled product should telephone the company for information on destruction of the product. Please call Eileen O’Neal at 317-228-5012 (Monday - Friday 9am - 5pm EST) for further information.

Duke cancer trials allegedly lacked proper clearances

January 28, 2011

After starting a misconduct investigation, suspending three clinical trials, and triggering an expensive Institute of Medicine (IOM) probe into the use of genomics technology in clinical trials, Duke University does not yet seem to be anyways near to moving on from the legal and ethical quagmire surrounding the work of cancer geneticist Anil Potti.

Today’s issue of The Cancer Letter reports that Duke has had auditors from the Food and Drug Administration (FDA) on its campus, potentially because the university failed to obtain its approval for the trials, which were based on Potti’s research. The trials did not involve testing new drugs on patients. However, Potti’s genomics technology – now known to be flawed -- was used to determine what drug patients would receive and The Cancer Letter reports that officials at the FDA – which regulates medical devices – regard themselves as having jurisdiction. Specifically, a clearance called an "Investigational Device Exemption"(IDE) was needed to cover use of the genomic chips used to test patients for biomarkers believed to indicate the drug sensitivity of their cancers.

Around 110 patients were enrolled in the trials. Duke administrators have been under fire over their response to concerns brought to their attention by external biostatisticans, specifically their decision to withhold a critical report uncovering data flaws from a review panel they had charged with reviewing Potti’s research.

The FDA is co-sponsoring the IOM probe with the National Cancer Institute, where officials had also raised concerns about Potti’s work while the trials were ongoing.
Sensitively for Duke, documents show how Potti’s co-author, Joe Nevins, tried to get an IDE for use of a closely related technology, apparently believing one was needed. Yet in other documents, Duke’s Institutional Review Board put N/A for non-applicable next to checkboxes intended to indicate whether this form of FDA clearance had been obtained.
The Cancer Letter also reports that a Duke center directed by Nevins has been shut down to allow him to concentrate on the investigations surrounding his work with Potti.
Image: West Campus/ Duke Photography

http://blogs.nature.com/news/thegreatbeyond/2011/01/duke_cancer_trials_allegedly_l_1.html

HIV Prophylaxis; CDC Offers Guidance for Use of Emtricitabine plus Tenofovir

The CDC has published interim guidelines for HIV prophylaxis using the combination drug tenofovir plus emtricitabine (marketed as Truvada) in men who have sex with men.
The guidelines, published in MMWR, follow a New England Journal of Medicine study that showed a 44% reduced rate of HIV acquisition in men who took the drug.

While final guidelines on pre-exposure prophylaxis are being developed over the next several months, the agency recommends the following:
Use of Truvada as a prophylactic measure should be limited to men who have sex with men.
Eligible patients should be at "substantial, ongoing, high risk" for HIV infection and should be screened for hepatitis B and other sexually transmitted infections.

Physicians should prescribe one tablet of Truvada daily with no more than a 90-day supply.
Risk-reduction counseling, condoms, and medication adherence counseling should also be provided.
The document also provides advice on patient follow-up while the drug is being taken and how to discontinue the drug.

LINK(S):
MMWR article (Free)
Physician's First Watch coverage of NEJM trial (Free)
Published in
Physician's First Watch
.
January 28, 2011

MRSA: What happens when antibiotics are overused ?

What happens when antibiotics are overused ?
This flash video written deliberately in an elementary format is rather clever, as it explains the overuse of antibiotics in relation to super bugs like MRSA .

.

(Click The Arrow To Navigate the Slide show)

Development of resistant Staphylococcus aureus over time

View more presentations from Tim Plante.

;

January 31, 2011
UK health agency warns over antibiotic resistance

LONDON (Reuters) - British health authorities issued new guidelines on Saturday to try to halt the spread of "superbug" infections that are resistant to even the most powerful antibiotics, known as carbapenems.
Carbapenems are heavy-hitting antibiotics often reserved as the last line treatment for illnesses like hospital-acquired pneumonias, urine infections or blood poisoning caused by strains of Klebsiella and Escherichia coli bacteria that are resistant to other antibiotics.
Several strains of these bugs are now also becoming resistant to carbapenems, something experts say puts modern medicine under threat.

"It is critical ... to understand how much of modern medicine - from gut surgery to transplants - depends on the ability to treat infection," said David Livermore, director of antibiotic resistance monitoring at the Health Protection Agency (HPA).
"If that ability is lost through resistance, then medicine will take a great step backwards."
HPA guidelines for all consultant medical microbiologists and infection control specialists across Britain will advise how hospitals should try to detect carbapenem-resistant bacteria, and stress how practices such as screening and isolating high risk patients can help contain infection spread.
The advice was drawn up after inquiries from specialist doctors about use of antibiotics after a superbug involving New Delhi metallo-beta-lactamase, or NDM-1, was found last year to have spread to Britain from Asia.

"The emergence of carbapenem resistance is a major public health concern and we hope this new guidance will help infection control specialists ... recognize, treat and prevent infections caused by bacteria with these resistances," Livermore said.
First described in 2008, NDM-1 is an enzyme that destroys carbapenems, also known as a carbapenemase. It has been found in a variety of bacterial types, including the Enterobacteriaceae family, Klebsiella and E. coli, all of which are common and can cause a range of infections.

Scientists from the Stockholm-based European Centre for Disease Prevention and Control (ECDC) said last November that around 77 cases of infections involving NDM-1 had been detected in 13 European countries.

A U.S. expert published a paper last month saying that cases of Enterobacteriaceae-containing NDM-1 had been found in the United States, Israel, Turkey, China, India, Australia, France, Japan, Kenya, Singapore, Taiwan and the Nordic countries.
Aside from NDM-1, other carpabenemases have also been detected in Britain and worldwide, the HPA said, including one known as Verona Imipenemase (VIM), another called Klebsiella pneumoniae carbapenemase (KPC) and another called OXA-48.
Experts have been warning for years that poor hospital practices and the overuse of antibiotics will boost the spread dangerous bacteria, but practices are changing only slowly.
The World Health Organization (WHO) now says there is an urgent need for new antibiotics to be developed, but drug firms are often reluctant to invest heavily into developing such drugs, given that they are often reserved for only the sickest patients and are therefore likely to generate only modest sales.

© 2004 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing, linking or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

.

Why You Shouldn't Beg Your Doctor for an Antibiotic

Antibiotic overuse creates superbugs that are resistant to treatment.

Feeling sick?

Your doctor may weigh the evidence and say you don't need an antibiotic. If you insist, chances are, she'll sigh, pull out her script pad, and give you one just to get your annoying self out of her office. Physicians are busy people who don't necessarily feel like giving you a lesson in Antibiotics 101 during your three-minute visit."Patients will, in many cases, insist that they be given an antibiotic," says Frank Myers, the director of clinical epidemiology at Scripps Mercy Hospital, in San Diego. Some even threaten to see another doctor if they don’t get the drugs.However, there are a lot of really good reasons why you should meekly leave the doctor's office empty handed, save for the standard advice to get enough fluids and bed rest.For one, antibiotics also kill off good bacteria in your body, which help to digest your food or maintain a healthy balance in your throat or genital tract. "You're not just killing bad bugs; you're killing good bugs," says Tom Campbell, MD, a family physician in Rochester, N.Y. When good bacteria die, it can cause diarrhea as well as yeast infections of the throat and vagina.

In recent years, there have been outbreaks of a potentially life-threatening intestinal bacterium called C. difficile, which can gain a foothold in people who are treated with antibiotics.In addition, antibiotic overuse creates superbugs that are resistant to treatment. Take methicillin-resistant Staphylococcus aureus (MRSA), which was recently responsible for some highly publicized deaths in teens and children. The staph strain is resistant to antibiotics such as methicillin, oxacillin, penicillin, and amoxicillin. The U.S. Centers for Disease Control and Prevention says that between 1999 and 2005, the number of MRSA-related hospitalizations increased 62%, from 294,570 to 477,927.Another dangerous bacteria is penicillin-resistant Streptococcus pneumoniae, or strep pneumo, a common problem with childhood ear infections. "This is much more difficult to treat because of antibiotic resistance, and it causes a lot of illness," Myers says. "It's a big problem with kids' ear infections and can also result in meningitis in both children and adults."The overuse of antibiotics has become so problematic that state health agencies around the world have created public-education campaigns—including advertisements on television, buses, and billboards—to warn both doctors and patients (and especially parents) about the dangers of antibiotic resistance.

Keep Reading............

.

Liver Heath: Prebiotics, probiotics and synbiotics was associated with significant improvement in minimal hepatic encephalopathy MHE

Synbiotic
A synbiotic is a supplement that contains both a prebiotic and a probiotic that work together to improve the “friendly flora” of the human intestine. As probiotics are mainly active in the small intestine and prebiotics are only effective in the large intestine. The prebiotic probiotic combination gives a synergistic effect called synbiotics.
.
Probiotics: The Facts
Probiotics are living microorganisms which work within your gastrointestinal (GI) tract to have a positive effect on health. Most probiotics are "good" bacteria like Lactobacillus, Acidophilus, Enterococcus, Bifidobacterium or Escherichia. Centuries of folklore suggesting the health benefits of ingesting dairy products which are fermented and contain live and active cultures are now scientifically supported. Probiotics can be founding a variety of dairy products (yogurt, most notably) and as dietary supplements (both powdered form and capsules).

Prebiotics: The Facts
Prebiotics can be manufactured (using enzymes to alter sucrose), isolated from plant sources (like chicory) and found as a naturally occurring substance in many foods. Prebiotics do not get metabolized in the stomach or absorbed in the GI tract. They are fermented by the microflora in the GI tract. Most importantly, prebiotics encourage the growth and increased activity of "good" bacteria within the intestines; thus, enhancing the effects of probiotics. The most well-known prebiotic is inulin, a dietary fiber common in plants like artichokes, asparagus and leeks. Prebiotics are often added to foods like cereal, breads, drinks and yogurt.

How They Work
Probiotics work in the body to balance the effects of potentially harmful bacteria, aid in digestion, decrease infections and even lessen certain allergic reactions. They strengthen the lining of the GI tract and help to stimulate the immune system. Prebiotics are non-digestible food ingredients which work within the intestinal tract to enhance the growth of "good" bacteria and increase your body's resistance to invading harmful bacteria or viruses.
Read more: The Differences Between Probiotic & Prebiotic

Intestinal Microflora
Bacteria and other organisms that live inside the intestines. They help digest food. Vitamins such as biotin and vitamin K are made by intestinal microflora. Also called gut flora, gut microflora, intestinal flora, and microflora.


Synbiotics Support Gut in Cirrhosis

HOUSTON—Cirrhosis patients with minimal hepatic encephalopathy (MHE) can use synbiotics (prebiotic-probiotic combination) to modulate the unbalanced, pathogenic intestinal microflora that commonly manifests in MHE, according to a recent meta-analysis.

Researchers from State University of New York, Buffalo, N.Y., and The University of Texas MD Anderson Cancer Center, Houston, published their review Jan. 20 online ahead of print in Alimentary Pharmacology and Therapeutics.

The scientists searched MEDLINE, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews for published studies in all languages, using a priori criteria, with pooled relative risk and heterogeneity estimated as the measures of association. In the nine studies meeting their inclusion criteria, the use of prebiotics, probiotics and synbiotics significantly reduced the pooled relative risk (RR) of no improvement of MHE (RR 0.40, 95% CI 0.32-0.50; P less then 0.001).

Their subgroup analysis revealed five studies with lactulose showed significant reduction of risk of no improvement of MHE (RR 0.34, 95% CI 0.24-0.47; P less then 0.0001) with no inter-trial heterogeneity.

In two trials, the use of probiotics and synbiotics was associated with significant beneficial effects (RR 0.41, 95% CI 0.26-0.65; P less then 0.0001 and RR of 0.51, 95% CI 0.32-0.80; P=0.004 respectively).

They found no major adverse events associated with any of the interventions, but probiotics and synbiotics were better tolerated than was lactulose.

They concluded the use of prebiotics, probiotics and synbiotics was associated with significant improvement in MHE.

Treating Hepatitis C In 2011; The Bible Of Links

Its time to roll out the "Bible of Links" for all those people who may be getting ready to contemplate treatment. If all goes well the two new HCV drugs, telaprevir and boceprevir should be ready for market by the end of this year. This blog has made an attempt to breakdown the data in order for you to ready yourself for that first treatment consultation.

..

From the moment of diagnosis the HCV experience begins; which can only be compared to "Mr. Toad's Wild Ride". The decisions start to pile up and fear ensues. This entire journey can be made easier if armed with information as you begin the whole process which includes testing, waiting for test results, waiting for more results, and finally moving onto a treatment decision.

Today's entry is a bible of links, easy to understand facts, that may make the ride a little less bumpy.
.
The New Updates May 2011
Monday May 23 the FDA Approved Telaprevir/Incivek For Hepatitis C , for more information see;Telaprevir/Incivek Prescribing Information and the Medication Guide

Friday May 14th the FDA approved VICTRELIS™ ( Boceprevir) for the treatment of Hepatitis C.

The HCV community has waited 20 years for a new drug and this drug will particularly give patients who treated unsuccessfully another shot at eliminating the virus.View the Prescribing Information and Medication Guide . Life is good !.

Patient Assistance Program
INCIVEK/Telaprevir and VICTRELIS (Boceprevir) Patient Assistance Programs

You may want a few fast facts on both drugs, you can view those here;Getting Ready; Telaprevir or Boceprevir ? .,
.May 1st- Also on the website is the New two part video from  Melissa Palmer, M.D. on Telaprevir (Vertex Pharmaceuticals) & Boceprevir (Merck), the new protease inhibitor treatments for hepatitis C (HCV).
,

The first link is a good starting point; it covers pre-testing, justification for treatment, response guided therapy and more; Hepatitis C Treatment; What Do I Need To Know?

The treatment protocol with boceprevir for instance will be complex and merits a look see. This link has been added to numerous posts on the blog, maybe at least twenty times, its an important one folks ; Potential for Misuse Is ‘Huge’

Before treatment begins there may be pre-testing which could include the "IL28B genotype test" if you have no idea what this test is, these links will clearly explain in an easy to understand format, I hope ; Hey, I have a question about this IL28B gene and hepatitis c treatment..... or (IL28B) Genotype Test Likeihood Of Achieving SVR. From HCV Advocate I bring you; The Gene that Predicts by the one and only—Alan Franciscus, Editor-in-Chief of the the HCV Advocate .

Lets not forget a link to the first silly video I made along with my imaginary friends; "He and She Bear". This video offers a bit of information about the ohhh soooo, confusing IL28B genotype test. Hey, reading all this data can be a bit much, watching a silly video is a nice break; Video: IL28B gene and hepatitis c treatment . A new video with the bears can be viewed on the website, the video covers treating with boceprevir, dosing and side effects.

Updated IL28B; May 2011
Telaprevir Ups Response Rates Across IL28B Genotypes in Hepatitis C

.

Quest Diagnostics Launches Hepatitis C Virus Therapy Test Based on IL28B Gene VariantsAccuType® IL28B test now available to physicians and for clinical trials research

.

Back in 2000 when I treated I clearly recall my biggest concern, the side effects. These news drugs will be used along with pegylated-interferon/ribavirin which we all know have side effects; as seen in clinical trials telaprevir and boceprevir have a few side effects of their own; Telaprevir and Boceprevir/Less Side Effects?

Treating this disease can be nothing short of overwhelming, filled with anxitey, damn challenging, it ain't easy folks. One of the first questions we all asked, or will ask... drum roll please... is..."Whats my chance for a cure ?" This link covers the stats for SVR while encompassing the different scenarios seen in HCV; Telaprevir and Boceprevir Understanding The Chance For A Cure

Here's video number two, the bears have become a little egotistical but its easy to watch while managing to clearly communicate the stats for SVR when treating with telaprevir in the triple therapy regimen; VideoTreating Hepatitis C With Telaprevir/SVR Stats 2011

This link is a great reference point for these news drugs; you'll find yourself going back to this information again and again, or not; New Future Hepatitis C Treatments: Interferon-sparing combinations

The newest entry on the blog covers the "proposed treatment guidelines", its a bit of information you won't want to miss. It also gives an idea of the cost of these new drugs.........ouch !

Hepatitis C:Treatment Guidelines"With The GOOD gene", The Cost Of Treatment Telaprevir/Boceprevir

Also Check Out:
HCV Advocate
HIV and Hepatitis
Natap

Medscape

.

This "Bible Of Links" will be listed on the sidebar of the blog, with updates as more information becomes available. Treatment was so much easier to understand ten years ago, as best described by the great Mr. Dylan; the times they are a changin ....

Updated May 23 2011

Hepatitis C:Treatment Guidelines "With The GOOD gene", The Cost Of Treatment Telaprevir/Boceprevir

Hi folks, the information/links provided here today is meant to provide you with a bit of information before you begin treating with one of these new HCV agents.

..

Below is an excerpt from this weeks medscape abstract/study : Hepatitis C: New Direct-acting Antivirals in Development : Treatment Guidelines. Listed is the approximate cost of treating with the new inhibitors, using a proposed system/class scale. The system includes "treatment guidelines" using pre-testing with the IL28B genotype test. I have added a summary of these alleles and response rates for anyone who hasn't yet read up on the whole "allele" phenomenon.

.

The Test

You may have ran across the buzz words "IL28B" and "allele". The new test is called IL28B genotype test, however this "genotype" test is not the same terminology used to describe the different (genotypes or strains) of HCV. The term "CC genotype" is used to describe the variation of IL28B gene. In the future this test may be used before treatment begins.

.

What is the test for ?

The test is exciting, as it may be predictive to treatment response. Currently people who are waiting to treat HCV are curious about the test, with the majority wanting to be tested to find out if they have the good "CC" allele. However, as mentioned below researchers/physicians are still waiting to see how these alleles will be associated with response rates to these new drugs. Although at this time insurance companies are not covering the cost of the test. In the future if the test proves to be beneficial through the ongoing trials that may/should change.

;.

What Are Alleles?..
Alleles are corresponding pairs of genes located at specific positions in the chromosomes. Together, alleles determine the genotype of their host organism. For example, the alleles for eye color are found on chromosomes 15 and 19, and depending on which alleles someone has, he or she may have blue, brown, green, gray, or hazel eyes, and sometimes a mixture of these traits is present.
.
What Are "C" and "T" Alleles ?
As mentioned above a person inherits two copies of each gene; one from each parent to make up each allele. The IL28B rs12979860 SNP has two alleles or variations which are recognized as "C" and "T"
.
Then What Is C/C or "CC" ?
.In Hepatitis C patients who have the C/C pattern simply means that they have two copies of the "C" allele.
.
What Is T/T or "TT" ?.
The same is true in Hepatitis C Patients who have the T/T pattern or two "T" alleles .
.
What Does This Mean To The Hepatitis C Patient?.
Hepatitis C Patients With The C/C pattern or two "C" alleles have the best response to HCV therapy
.
As for the T/T pattern or two "T" alleles they have the least response to therapy. .
.
What If A Person Has The C/T pattern?.
The C/T pattern would mean the person has one copy of each allele. These people would fall somewhere in between
.
The bottom line.........
TT - Poorest response to Hepatitis C treatment.

CC - Best response to Hepatitis C treatment.

CT - Somewhere in between TT and CC alleles.
.,
Also this blogger made a little video which you may find less...boring then this blog entry.

Video: IL28B gene and hepatitis c treatment

.

With good news.... comes bad news, the concern is that if a person has the bad "TT" allele, the insurance companies may refuse to pay for treatment. Another controversy, or should I say speculation could come from Merck.

.,..

What controversy?

The drug company Merck who is behind boceprevir seems to have the intellectual rights to IL28B genotype testing. In clinical trials boceprevir had a four week lead in with standard of care. (patients started with four weeks of pegylated interferon/riba before adding boceprevir). I can't say what this all means to us folks, maybe nothing. However, if IL28B testing becomes standard could physicians be persuade by insurance companies to use boceprevir over telaprevir ?

, .

The analogy goes like this;

1-IL28B testing

2-Test shows the "CC" allele (good allele)

3-Start with standard of care

4-Four week early response (RVR) continue on with Standard of care?

5-No early response....add boceprevir ?

,

This isn't a bad way to go, why add a third drug if its not needed. However, where does that leave telaprevir ?

.

That brings me to this, yesterday on the blog in an entry entitled "New Future Hepatitis C Treatments: Interferon-sparing combinations " it was noted;

.

"The addition of a protease inhibitor to pegylated interferon plus ribavirin is associated with increase in efficacy and shortened duration of therapy in patients with HCV Genotype1 and is likely to become the new standard-of-care. However, triple therapy will not be suitable for patients with non-1 HCV infection. "

.,

At this point it appears that genotype 1s will be treating with the new drugs. We can only wait to see if the other genotypes will also be using the new agents. A prudent assumption could be that this applies to only naive 2 and 3 genotypes; people who are treating for the first time, as discussed in the "Treatment Guidelines" below.

Genotype 3's noted in the post ;

"Moreover, although telaprevir has similar antiviral activity against HCV Genotype 2, this agent has no effect in patients with HCV Genotype 3 infection."

I assume this is the small study they were referring too.

.

Also mentioned in the "New Future Hepatitis C Treatments: Interferon-sparing combinations " data was that "Genotype 1" patients who do not respond to this new triple therapy will have developed resistance to protease inhibitors.

.

Listed below is an excerpt from medscape/entitled: Hepatitis C: New Direct-acting Antivirals in Development : Treatment Guidelines. Listed in the excerpt is the approximate cost of treating with the new inhibitors, using a proposed system/class scale. The system includes pre-testing with the IL28B genotype test. However, as mentioned below researchers/physicians are still waiting to see how these alleles will be associated with response rates to these new drugs. I have added a summary of these alleles and response rates for anyone who hasn't yet read up on the whole allele phenomenon.

.
Updated; As reported On Feb 25 2011

Scripps Health ;IL28B Genetic Testing to Hepatitis C Patients Now Available

. .

..

The abbreviations used in medscapes article are as follows;

.

CC, IL28B allele genotype C/C;

CT, IL28B allele genotype C/T;

IT, interferon tolerant;

TT, IL28B allele genotype T/T.

.

From Medscape..............

.

Hepatitis C: New Direct-acting Antivirals in Development : Treatment Guidelines

.
Owing to the side-effect cost of DAAs and the risk of development of drug-resistant viral strains, it will be necessary to guide treating physicians through a growing maze of confounding factors. These will likely not only include new drugs but also important predictive tests and relevant mutation analysis.

.

One such predictive test is the IL28B genetic polymorphism, which has recently been reported to be associated withSVR by three separate groups [Ge et al. 2009; Suppiah et al. 2009; Tanaka et al. 2009].

.

The IL28B genotype will become a commercially available polymerase chain reaction assay in 2010 and may be helpful for decisions using SOC treatment. It is unknown if the C/C, C/T, and T/T alleles of IL28B will be associated with response rates to DAAs and this information will need to be carefully collected in ongoing trials.

.
In Tables 2 and 3, a simple classification system is proposed that might permit physicians to solidify decisions regarding therapy.

.

Table 2. A proposed classification system for the treatment of hepatitis C virus in the direct-acting antiviral era.

.
Class I: treatment naïve, IT, G2/3, G1 low viral load, and/or CC allele (20–25% of US patients)

.
Class II: treatment naïve, IT, G1 high viral load, or CT/TT allele (40–50% of US patients)

.
Class III: G1/4 and G2/3 relapsers and nonresponders to current standard of care who become RNA undetectable by week 12 of treatment (20% of US patients)

.
Class IV: Class IIIs who do not become undetectable by week 12, interferon-intolerant patients and all treatment failures from treated Classes I–III (30% US patients assuming 5% from Classes I and III, and 10% from Class II)

.
CC, IL28B allele genotype C/C; CT, IL28B allele genotype C/T; IT, interferon tolerant; TT, IL28B allele genotype T/T.

.

.

Table 3

.

*Costs assume US $25,000/year for standard of care, likely use of growth factors for extended duration therapy, and costs of direct-acting antivirals less then us $25,000/regimen.

.

Abbreviations

SOC, standard of care;

SVR, sustained virologic response.

AWP ; average wholesale cost;

NS5B pol, NS5B HCV polymerase inhibitor;

PI, NS3/4 hepatitis C virus protease inhibitor;

.

Class I SOC×24 weeks SVR=80–90% Cost=US $25,000 (AWP)

.

Class II PI+SOC×24 weeks SVR=80% Cost less then US $50,000*

.

Class III PI+SOC×48 weeks SVR=70–75% Cost more then US $50,000 but less then US $100,000*

.,

Class IV PI+NS5B pol+other agents SVR=nil (lifetime suppression) Cost less then US $100,000*

.,

In this proposed system;

.

Class I patients would be those with a very high chance of SVR with SOC therapy for 24 weeks, that is, treatment naïve, interferon-tolerant patients with genotype 2/3, or genotype 1 infection with low viral loads or the C/C IL28B allele [Thompson et al. 2009].

.

As these patients would have an 80–90% probability of cure without the risk of additional side effects or the additional cost of DAAs, they might be well served to be treated with current SOC alone. These patients represent approximately 20–25% of the US population with HCV [Ghany et al. 2009].

.
Class II

patients might be those who are treatment naïve, interferon-tolerant with genotype 1 who have high viral loads and/or have C/T or T/T IL28B alleles. These patients would be less likely to have an SVR with current SOC but would have approximately a 75–80% chance of an SVR with the addition of an NS3/4 protease inhibitor followed by consolidation therapy for a total of 24 weeks (if an RVR is attained). The added cost of DAA therapy and the risk of side effects would need to be considered in these patients, who represent the majority of the US HCV population (40–50%) [Ghany et al. 2009].

.

Class III

patients would be those requiring 48 weeks of total therapy in order to attain an SVR with SOC and protease inhibitor therapy, such as relapsers and nonresponders of all genotypes, and those in Class I who do not attain an RVR. It would be important to establish a limit on exposure to protease inhibitor therapy in this group as many who are interferon refractory would not clear virus permitting the emergence of resistance. Although this period will require refinement in the future it appears to be 12 weeks based on the data we have presented herein. These patients are prevalent in practices but actually do not represent a majority of the infected population, certainly no more than 20%. It would be anticipated that half of these patients would not attain an SVR based on the data seen in treatment-failure patients Table 2.

.
Class IV

patients would include Class IIIs who do not become undetectable by week 12, interferon-intolerant patients and all treatment failures fromtreated Classes I and II. This could be up to 30% of the US population infected with HCV based on the SVR rates proposed above. These patients would probably be best served by waiting for the availability of combination therapy with an NS3/4 protease and either an NS5B polymerase, an NS5A inhibitor, a cyclophilin inhibitor, or another interferon-free combination regimen.

.

The goal of therapy in these patients would be viral eradication but this is not likely to be an attainable outcome for most. Instead, viral suppression with cessation of histological injury will likely be the new goal in these patients. As such, the risks for resistance and the cost of long-term therapies will need to be major considerations in this population Table 3.

.

Links for the full abstract and text;

,

Hepatitis C: New Direct-acting Antivirals in Development : Treatment Guidelines

.
Abstract and Introduction
Protease Inhibitors
Polymerase Inhibitors
Ribavirin Analogues
Other Direct-acting Antiviral Drugs
Other Novel Compounds
Treatment Guidelines

Conclusions

.

Also See;Treating Hepatitis C In 2011; The Bible Of Links

,