IL28B testing and Boceprevir

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IL28B testing and Boceprevir

I just came from facebook, and mentioned a great summary on this months EASL conference at NATAP, written by Mr. Jules Levin.http://www.natap.org/2011/EASL/EASL_37.htm In his summary he talks about drug resistance and the news looks good, which is so important. A must read summary! . He also touched on a topic I have been concerned about and even made an attempt at writting a small article on the subject; IL28B and the possible outcome for patients who undergo the test.. Related On The Blog; Expensive new hepatitis c drugs may restrict use in some countries I'll include the article in this entry. Here is a quote from Mr. Levin's summary;

Another issue being discussed in the wake on much data reported here on how IL28B affects treatment outcomes with peg/rbv, and triple therapy with an oral HCV protease+peg/rbv is what is the real usefulness of IL28B testing and; how it will be used by clinicians and; treaters and of note payers in the USA and most crucially in europe where payers are likely to be more stingy in support of boceprevir and; telaprevir use with peg/rbv. There was at this EASL to me surprisingly quite a lot of talk about using a lead-in of peg/rbv to block use of boceprevir or telaprevir, in the sense that if a patient had a good peg/rbv response at week 4 they could continue peg/rbv and NOT add boceprevir or telaprevir. I do not think that scenario is in the best interest of patient outcomes and; do not think this will be implemented in the USA. In the USA I think payers will appreciate the cost-effectiveness of using the best treatment and using an oral PI plus

peg/rbv provides the best opportunity for patients to achieve SVR and to shorten duration, remember that in genotype 1 48 weeks remains the duration standard of care and adding the protease increases the number of patients achieving SVR and can shorten duration of therapy to 24 weeks, which obviously is a major benefit.

This is what my concern is............Is IL28B Testing A Threat To Telaprevir Or To Patients ?Dec 2010On the blog and website IL28B testing has been an important hot topic over the last year. It will change the way we treat hepatitis C. People who carry a particular allele of the IL28B gene have a good chance of reaching SVR = (Sustained Virologic Response) when treating with standard of care= (peginterferon and ribavirin) therapy. .. The question is will these people need a protease inhibitor? The bigger question is will insurance companies pay to treat with telaprevir/boceprevir or a protease inhibitor in these individuals who have the good "CC" allele; best response to Hepatitis C treatment ? The concern is these patients may be started on standard of care without the option of a protease inhibitor. This is only in theory and until the FDA approval of telaprevir/

boceprevir we can only speculate. What about those people who carry the TT allele; which has the poorest response to treatment. This group of people will more than likely be offered a protease inhibitor.What will the final treatment protocol be when IL28B testing becomes standard ? If you remember in the boceprevir RESPOND-2 study all patients underwent a 4-week lead-in phase of standard therapy (peginterferon/ribavirin for four weeks) before adding boceprevir. (Hold that thought we will return to boceprevir in a moment) , Think about this, before starting treatment with boceprevir you're tested for IL28B and you have the good allele "CC". You begin therapy; after four weeks on standard therapy you have an early response (RVR) . Could a pattern begin to emerge in that people tested prior to treatment for IL28B (having "CC") and who achieve a four week early response be kept on standard therapy,

do these individuals need a protease inhibitor? Will insurance companies seize the opportunity to cut costs by refusing to pay for a protease inhibitor for these people? Especially in the event of socialized medicine or standardized care. In published data 30% of patients carrying the "CC" allele stand a very good chance of being cured with standard of care. The buzz is that the FDA is working with Vertex in order to understand the impact of IL28B genotype on anti-viral activity . Another factor is Merck who is behind boceprevir seems to have the intellectual rights to IL28B testing. ..LabCorp Gains Rights to Merck & Co.'s IL-28B Polymorphism IP for HCV Therapy Predictive Test http://www.genengnews.com/ /Merck has granted LabCorp a nonexclusive license to use the IL-28B polymorphism in a commercial test to help predict an HCV

patient's response to peginterferon alpha-based therapy. Merck will receive an up-front fee from LabCorp plus royalties on sales of tests covered under the deal. LabCorp has already developed an in vitro assay to identify the IL-28B polymporphism in HCV patients. An association between the polymorphism and peginterferon alpha response was identified by Merck and collaborating scientists through a genome-wide association study of nearly 1,700 HCV genotype-1 patients, the firm points out. The IL-28B link with HCV therapy identified through the Ideal study was first reported last year, and full data from the trial was published in Gastroenterology in May. Merck says it plans to provide a limited number of nonexclusive licenses to the IL-28B polymorphism to established diagnostics companies. Global sales of the firm's peginterferon alfa-2b HCV therapy Pegintron were $186 million in the first quarter of 2010. This brings us back to "Merck's

boceprevir" and their four week lead in with standard of care. 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 ? It could happen because the protocol for boceprevir thus far is the four week lead in. So the analogy goes like this ?1-IL28B testing2-Test shows the "CC" allele (good allele)3-Start with standard of care 4-Four week early response (RVR) continue on with Standard of care5-No early response....add boceprevir ?Where does that leave telaprevir?Where does that leave us ? Well, possibly it could mean standard of care in those people with a good ol' gene.Understanding The IL28B Gene and TestingWhat is a gene?A gene is the basic physical and functional unit of heredity. Genes, which are made up of DNA, act as

instructions to make molecules called proteins. In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. The Human Genome Project has estimated that humans have between 20,000 and 25,000 genes.Every person has two copies of each gene, one inherited from each parent. ..Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different between people. .Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s unique physical features.How is the IL28B gene related to Hepatitis C ?Variations in the IL28B gene have recently been linked to better treatment response among people with chronic hepatitis C virus. 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. SourceWhat 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 regonized 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.Then 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 Heptitis 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.Summarize All Of This PleaseTT - Poorest response to Hepatitis C treatment.CC - Best response to Hepatitis C treatment.CT - Somewhere in between TT and CC alleles.Non-genetic and genetic factors play a part in determining whether PEG-IFNalpha/RBV therapy will work. Recent research has identified several inherited variations near the interleukin 28B (IL28B) gene that could eventually help doctors identify those people with hepatitis C for whom the standard treatment is doomed to fail.See: Response to Hepatitis C Treatment** Note: It has been proven that people of European descent more

commonly have the C/C pattern this may explain why white patients infected with HCV respond better then black patients.Is There A Test For The IL28B Gene?LabCorp Launches Interleukin 28B Polymorphism (IL28B) Genotype Test to Support Individualized Treatment Decisions for Patients with Hepatitis C Viral Infection.Service Announcement As reported On Feb 25 2011 Scripps Health ;IL28B Genetic Testing to Hepatitis C Patients Now Available From HCV Advocate Note: The term CC genotype used to describe the variation of IL28B is not same as the term used for

different strains of HCV (called genotypes)–numbered 1 through 6. ..

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