HCV Research and News

March 6, 2012

Idenix Pharmaceuticals Announces Declaration of a Patent Interference by the USPTO

CAMBRIDGE, Mass., March 6, 2012 /PRNewswire/ -- Idenix Pharmaceuticals, Inc. (NASDAQ: IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced that the United States Patent and Trademark Office (USPTO) declared a patent interference between Idenix's U.S. Patent Application no. 12/131,868 and Pharmasset Inc.'s (acquired by Gilead Sciences) U.S. Patent no. 7,429,572, both related to certain nucleoside compounds useful in treating patients with hepatitis C virus (HCV) infection.

"We are confident in our robust intellectual property position. While the claims in this interference are not related to our nucleotide inhibitor, IDX184, or any other candidate in our pipeline, we believe it is important to deepen the strength of our existing patent portfolio," said Ron Renaud, Idenix's President and Chief Executive Officer.

A patent interference is an administrative proceeding conducted by the USPTO in order to determine which party is entitled to a patent when two or more parties claim patent rights to the same technology. Under current U.S. law, a patent is awarded to the first party to invent a particular technology, subject to certain limitations. The applicant who filed the earlier patent application is referred to as the senior party in the patent interference and the applicant with the later filing date is referred to as the junior party. The junior party bears the burden of proof to demonstrate that it invented the technology in question before the senior party.

In this case, the USPTO has initially determined that Idenix is the senior party and that Pharmasset Inc. (acquired by Gilead Sciences) is the junior party.

ABOUT IDENIX

Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical Company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with hepatitis C infection. For further information about Idenix, please refer to www.idenix.com.

FORWARD-LOOKING STATEMENTS

This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the Company's position in its interference proceedings with Gilead Sciences. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the Company's intellectual property rights and potential pipeline candidates. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's annual report on Form 10-K for the year ended December 31, 2010, and the quarterly report on Form 10-Q for the quarter ended September 30, 2011, each as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the Company files with the SEC.

All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.

Idenix Pharmaceuticals Contacts:
Kelly Barry (617) 995-9033 (media)
Teri Dahlman (617) 995-9807 (investors)

SOURCE Idenix Pharmaceuticals, Inc.

Some liver damage can be reversed through exercise

Updated: 2012-03-05 16:42:38 CST

Most people associate liver problems like cirrhosis with years of heavy drinking. However, people who have never touched a drop of liquor in their lives are increasingly receiving unhealthy liver panel test results. The cause is obesity.

Excess body fat is a risk factor for a condition known as non-alcoholic fatty liver disease. It occurs when the liver is unable to clear the excess fat from the blood and instead stores it. This can cause scarring and loss of healthy function, according to the Mayo Clinic. However, it is possible to reverse the condition.

Experts from the Baylor College of Medicine recently told the school's news source that every pound a person loses gets them one step closer to healthy liver function. This can be accomplished through a healthy diet and exercise.

"Losing 10 percent body weight primarily reduces fat inside the abdomen, which triggers a significant amount of liver healing," Dr. John Vierling told the news source. "It's easy for people to get discouraged when it comes to weight loss, but understanding that every pound lost is helping your liver heal is motivating."

Source

National Advocates Speak Out About Bio-medical Research Priorities

By Srebrenka Kac on Mar 6, 2012

Americans must demand priority for bio-medical research with the clear focus on a greater parity in funding for chronic conditions. Bill Remak, FAIR Foundation member and patient advocate, passionately urges all patients to take action and voice their concerns by writing and calling their representatives about the disparities in research funding.

The new sample prepared letter can be found here. Also visit the FAIR Foundation website to get the facts.

Bill Remak, a cancer and 2X liver transplant survivor, a former scientist, nationally recognized patient and research advocate, FAIR Foundation Board Member, Board member of the California Chronic Care Coalition and Chairman of the National Association of Hepatitis Task Force is carrying the torch together with many prominent healthcare leaders and consumer advocates on this crusade. He urges people to use the new sample letter on the FAIR Foundation website to convey this important unmet need to their representatives.

The FAIR Foundation is a national non-profit organization with thousands of members and millions of supporters in all fifty states and the District of Columbia. FAIR’s Board of Directors consists of twenty-seven transplant surgeons, medical directors and patient advocates.

Remak states, “Chronic conditions that impact major segments of our society deserve a greater allocation of medical research funds. Our federal and state governments need to do better in designating medical research to prepare for better health outcomes for our workforce which will improve production and quality of life for future generations.”

Remak further clarifies, “American tax dollars fall short in providing parity and financial resources for the most devastating chronic conditions in our aging society allowing cancer, heart disease and diabetes and others to erode at every family’s economic prosperity.”

The former United Nations (WHO) World Health Organization Director, Lee Jong-wook, after exhaustive research concluded in the 2005 WHO global report the following statement which supports Remak’s claim:

“The lives of far too many people in the world are being blighted and cut short by chronic diseases such as heart disease, stroke, cancer, chronic respiratory diseases and diabetes. This is no longer only happening in high income countries. Four out of five chronic disease deaths today are in low and middle income countries. People in these countries tend to develop diseases at younger ages, suffer longer – often with preventable complications – and die sooner than those in high income countries.” Ref # 0

The same 2005 WHO report also found, in the section titled “The Urgent Need for Action,” the three top estimators of the economic impact of chronic diseases listed below. We highlight the last one as an underlying reason as to why funds should be dedicated adequately to chronic illnesses and diseases of aging for bio-medical research:

A) Chronic diseases are a major cost and a profound economic burden to individuals, their families, health systems and societies.

B) These costs will increase without the implementation of effective interventions.

C) Investment in interventions to control the burden of chronic diseases will bring appreciable economic benefits.

Wikipedia provides this well worded definition: Medical research can be divided into two general categories: the evaluation of new treatments for both safety and efficacy in what are termed clinical trials, and all other research that contributes to the development of new treatments. The latter is termed preclinical research if its goal is specifically to elaborate knowledge for the development of new therapeutic strategies. A new paradigm to biomedical research is being termed translational research, which focuses on iterative feedback loops between the basic and clinical research domains to accelerate knowledge translation from the bedside to the bench, and back again. Medical research may involve doing research on public health, biochemistry, clinical research, microbiology, physiology, oncology, surgery and research on many other non-communicable diseases such as diabetes and cardiovascular diseases.

The increased longevity of humans over the past century can be significantly attributed to advances resulting from medical research. Among the major benefits have been vaccines for measles and polio, insulin treatment for diabetes, classes of antibiotics for treating a host of maladies, medication for high blood pressure, improved treatments for hepatitis C, statins and other treatments for atherosclerosis, new surgical techniques such as microsurgery, and increasingly successful treatments for cancer. New, beneficial tests and treatments are expected as a result of the Human Genome Project. Ref #2

The journal of the American Medical Association states that in the United States the data from 2003 suggest that about 94 billion dollars were provided for biomedical research. The National Institutes of Health and pharmaceutical companies collectively contribute 26.4 billion dollars and 27.0 billion dollars, respectively, which constitute 28% and 29% of the total. Other significant contributors include biotechnology companies (17.9 billion dollars, 19% of total), medical device companies (9.2 billion dollars, 10% of total), other federal sources, state and local governments. Foundations and charities, led by the Bill and Melinda Gates Foundation, contributed about 3% of the funding. Ref #1

Recently on February 13, 2012, Francis S. Collins, M. D., Ph. D., Director of the National Institutes of Health wrote in his letter introducing the 2013 NIH Budget Plan, “In the face of growing global competition investment in biomedical and behavioral research and the scientific workforce will propel scientific discovery for the benefit of human health and the U. S. economy, both now and in the future.” Ref #3

Remak’s conclusions that disparities in research funding are negatively impacting people with chronic diseases are clearly validated by the evidence presented.

Source

Patients with hepatitis C virus infection who adhere to their drug regimen are more likely to show long-term benefit

Less than optimal adherence by a patient infected with hepatitis C virus (HCV) to a regimen of pegylated interferon and ribavirin decreases the likelihood of finding no detectable viral load 24 weeks after the medication is stopped (a sustained viral response), according to a new study. The standard of care for HCV infection—twice-daily treatment with oral ribavirin and weekly subcutaneous injection of pegylated interferon 2a or 2b—can eradicate the virus, halt or regress liver fibrosis, and reduce the risks for cirrhosis of the liver, hepatic decompensation, and malignant liver cancer. However, the treatment is complex and requires frequent laboratory monitoring of the viral response and possible adverse effects.

The researchers found that patients infected with HCV genotypes 1 or 4 were more likely to have an early virologic response, a 100-fold reduction in viral load, over the initial 12 weeks of treatment with 91–100 percent adherence (63 percent of 2,187 patients). This contrasted with patients with 40 percent adherence or less (37 percent of 68 patients). Patients with HCV genotypes 2 or 3 with adherence of 91–100 percent were also more likely to exhibit EVR (91 percent of 713 patients) than those with adherence of 40 percent or less (67 percent of 18 patients). For patients who showed a virologic response by 24 weeks of treatment, 47 percent of those infected with HCV genotype 1 or 4 and 69 percent of those infected with HCV genotypes 2 or 3 achieved a sustained viral response.

The researchers analyzed electronic medical record data from the National Veterans Affairs (VA) Hepatitis C Clinical Case Registry, together with medication information on these patients from the VA pharmacy database. A total of 5,706 patients treated with pegylated interferon and ribavirin were included in the study. It was funded in part by a grant (HS10399) from the Agency for Healthcare Research and Quality to the University of Pennsylvania Center for Education and Research on Therapeutics (CERT).

For more information on the CERTs program visit http://www.certs.hhs.gov.

More details are in "Relationship between adherence to hepatitis C virus therapy and virologic outcomes," by Vincent Lo Re III, M.D. M.S.C.E., Valerie Teal, M.S., A. Russell Localio, Ph.D., and others in the September 20, 2011, Annals of Internal Medicine 155(6), pp. 353–360.

Source

Roche improves cutting-edge portfolio for early hepatitis C diagnosis and targeted treatment

Rotkreuz, 06 March 2012

Elecsys® anti-HCV II immunoassay from Roche receives CE mark

Roche now offers a fully updated state-of-the-art portfolio for the early detection of hepatitis C virus (HCV) infection and personalized disease management. The improved diagnostics and patient monitoring solution provides an one-stop shop for HCV testing with unprecedented performance in early infection and ease of use, allowing clinicians to work efficiently and to suit individual patient treatment.¹

Early detection of HCV infection is vital in order to provide consolidated care of acute and chronic infection, and adequate treatment of drug response monitoring are crucial to overall therapy success. Patients undergoing a peginterferon alfa-2a and ribavirin therapy can be monitored precisely by real-time PCR measurement.

With the novel Elecsys anti-HCV II immunoassay on cobas® e modules Health Care Professionals get a cutting-edge tool for the early qualitative detection of antibodies against HCV. The updated assay with CE mark approval delivers enhanced convenience, specificity, increased reliability and consistency for improved efficiency in screening patients and blood donors.¹

Following the identification of HCV antibodies, testing for HCV RNA, which is a crucial marker in the management of hepatitis C, confirms the infection and aids clinicians in predicting treatment response. In December 2011, Roche also received the CE mark for its HCV RNA qualitative and quantitative tests, which offer sensitive detection of HCV RNA and viral load measurement for predicting drug response on the COBAS® AmpliPrep/COBAS® TaqMan® fully automated platform.

As Personalized Healthcare has already begun to add true medical value for health professionals and patients, Roche’s novel portfolio underlines the clear shift from an ‘equal shares for all’ principle toward a target oriented and response-guided therapy approach. Out now, the updated portfolio of HCV testing and monitoring from Roche delivers a convenient set of tools to laboratories and clinicians to improve patient care.

About hepatitis C

World Health Organization figures show that around 200 million people globally are infected with HCV, which is particularly concentrated in the blood. Around 170 million people are chronic carriers of the virus, which can lead to cirrhosis, liver failure, and hepatocellular carcinoma.² Identifying HCV infection is difficult because there are often no symptoms. Most cases go undetected and there is currently no vaccine to prevent infection. Many countries are currently unable to screen blood donations for infections such as hepatitis C.³

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalized healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2011, Roche had over 80,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 42.5 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References

1)Esteban Juan et al (2012). Elecsys anti-HCV II: a sensitive and specific assay for diagnosing hepatitis C virus (HCV) infection. In: Hepatology, Vol. 6, N° 1; Zitzer Heike et al (2011). Clinically Relevant HCV RNA Viral Load Results Using a Sensitive, Quantitative Assay. 7th European Meeting on Molecular Diagnostics, October 12-14, 2011, Scheveningen, the Netherlands
2)World Health Organization. Hepatitis C. Fact sheet N°164. Retrieved from http://www.who.int/mediacentre/factsheets/fs164/en/ on February 19, 2012.
3)World Health Organization. Blood Safety and Availability. Fact sheet N°279. Retrieved from http://www.who.int/mediacentre/factsheets/fs279/en/index.html on February 19, 2012.

Source

Bonnie and Charlie's Journey

by Bonnie Buckley

July 4, 2007

The day started out like any other day but wow would it ever end with a bang . When I woke up for work Charlie (hubby) was gone to work hours earlier and I went to shower and get our daughter Kayla up for highschool.Something we did on a regular daily basis. I came out of the shower and noticed Charlie was back home in bed and looked horrible sick. I got him some meds and gingerale and headed to drop Kayla at school and me at work. Kayla called me at work around 2pm when she got home from school and said her dad was terribly sick with severe stomach pains and vomiting and looked a yellowy color.This seemed to come out of nowhere but as I look back he hadn’t been well for a very long time but he wasn’t a complainer and never ever took time off work He never was sick or at least never said when he was so this was scary different. As he seldom got sick or attended an emergency department an alarm bell sounded when Kayla asked him if he would go to our local hospital to be checked out and he said yes . It was July … who has the flu in July ???? I left work early and met them at the emerg where the doc was amazing and was doing a whole slew of testing on him.One of the tests was for hepatitis C . The doc asked if he was high risk and as he had never been an IV drug user or had a blood transfusion, etc, etc, we said no but lets do the test anyway to rule this out. So we wait ……….

The doc finally came in and said Charlies blood work was not good, his liver numbers were way high and his spleen was huge and swollen very bad and other blood work was way off normal limits The doc said his assumption at that point was Leukemia or liver failure. Wow what a choice !!!! Now it was all starting to make sense …. The decade of leg muscle cramps, the headaches, the tiredness constantly, the memory issues, he couldn’t have more than 1 beer and he would be slurring his words and staggering all over the place. I always thought he was lying to me when he would say he had only had a beer or 2 at most. He had been to the family doc a few times with these complaints, not all at once but he had been there asking about the issues periodically , only to be told to drink more milk for the cramps, get more sleep for the tiredness, forgetfulness and he was under too much stress which causes headaches. Not once did she do any blood work on him !!!!! It was one of the worst nights of my life ( or at that time I thought it was but I sure didn’t forsee the nights of the future). He was referred to an internist here in Guelph the next day and I was not happy with the investigation plan so I made us an appointment with the family doctor and demanded he be sent to a large city center hospital familiar with liver issues. At this time we still didn’t know the results of the hep c test and really gave it no further thought. As we waited for the referral appointment notice to come I searched up everything I could on liver disease and leukemia. Scary stuff I remember thinking , and a lot of talk of hep c …. Hmmmmm ….. I wondered . The tests finally came back and it wasn’t leukemia but it was late stage cirrhosis of the liver and the hep c test came back positive !!!! We were shocked , what did this all mean anyway???? Well he had genotype 3b hepatitis c and now it was time to digest all this life changing information and that was a huge task. Where the heck did he get hep c from and why the heck did the family doc not diagnose this decades earlier when he had all these vague symptoms. A blood test panel would have possibly caught the wacky numbers . But we had to go forward and to play the blame game wasn’t productive as we were fighting for his life which was far more urgent. Our appointment for Charlie at London Health Sciences Hospital in London Ontario was booked for only a couple of months down the road and that was a short wait considering the wait to go see a specialist in Ontario is dismal . He was put on Furosimide for the ascites and he had to have 2 litres of fluid drained from his stomach as well . He was put on a low sodium diet to help as well with the swellings and we waited ….. It was the end of August 2007 when we first went to London to the hepatologists. He was scheduled for numerous blood tests, and ultrasound, a CT scan and was put on new medicines . They asked about the risk factors for the hep c and honestly we weren’t sure how he contracted it but I did get a feeling that they thought we were just neglecting to disclose some of his drug using past , which there was definitely some marijuana use on a regular basis but never anything snorted or injected. He had 2 tattoos that had been done in the basement of a work buddies house that were suspect but for me it didn’t matter how or where he contracted hep c …. He had it and no one deserves the suffering or stigma associated with hep c. It was a wait and see and monitor the situation approach that the docs in London decided to take. No treatment for hep c until they saw if they could stop the progression or at least slow down the liver decline. As a wife and caregiver it was heartbreaking and scary to be going through this. I watched my mother take care of my father my entire childhood as he suffered from a rare blood disorder that eventually took his life and I saw and felt the heartache and agony and here I was experiencing it all over again as a wife this time. It was awful watching such a strong, happy, wonderful man deteriorate before my eyes. I had 3 children when I first met Charlie back in 1984 and he was my friend at first , but we fell in love and I do believe we are soulmates. He adopted my 3 children as we had been abandoned by my ex husband the year prior and then we married and had our baby girl together in 1989. Life was good back then and now we were faced with this !!!

As the months passed by Charlie became weaker and sicker and spent a lot of time in bed and his memory was fading fast. I would have to explain simple things to him time and time again and it was sad and frustrating at the same time. I felt so bad for being snappy with him sometimes but he was frustrating and I have never been a very patient person. I loved him so much and it drove me crazy to see him wasting away.As his body was filling with toxins it was almost impossible to sleep in the same room with him. The odor coming from his skin was really bad and some nights I would have to sleep at the end of the bed so my head was near the open window. I felt so bad . He would sometimes say to me “do I smell that bad again?” I would tell a fib and say no he didn’t smell that bad it was just me having a hard time sleeping that night. The feelings of defeat, heartache, fear, lonliness and anger were overwhelming and I sometimes wish I would just go to sleep and never wake up, it would be easier I would tell myself, the hurt would go away finally. But then out of nowhere I would gather strength and determination to go on another day and fight with all I had to make someone help him. He couldn’t die on me I kept thinking, he cant leave me here alone. Someone must be able to fix him, this isn’t fair and Im not accepting this . His liver was failing and he was now in end stage cirrhosis of the liver by Feb of 2008 and the docs in London decided that he needed to go for a liver transplant assessment to see if he would be able to tolerate hep c treatment or if he should be placed on the transplant list right away. So we were sent home to wait for the call that would book the 4 days of ultrasounds, blood tests, CT scans, counselling appointments and psychiatric appointments. Life was hard for all of us while we waited for answers and a concrete plan , all the while watching him slip away bit by bit and helpless to do anything to make him better. This was so unfair I kept telling myself , this is nonsense, how can he be so sick , so fast at 46 years old !!!! Soon hopefully we would be London bound for the 4 day assessment and hopefully have a plan in place to make this better , at least that’s what I thought ……… The journey through the transplant assessment and ups and downs and the outcome of the process is coming up shortly … stay tuned and thanks for visiting .

Bonnie Buckley

CROI 2012: Data from Phase 2 Study of an INCIVEK® Combination Regimen Showed 74% of People Co-Infected with Hepatitis C and HIV Had Undetectable Hepatitis C Virus 12 Weeks After Treatment Ended (SVR12)

March 6, 2012
- INCIVEK was well tolerated with commonly used Atripla- and Reyataz-based HIV treatment regimens, and no patients experienced HIV breakthrough -
- Enrollment is ongoing in Phase 3 study evaluating 24- and 48-week treatment durations in people who are co-infected -
SEATTLE--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced interim results from an ongoing Phase 2 study designed to evaluate the safety and tolerability of INCIVEK^® (telaprevir) tablets in combination with pegylated-interferon and ribavirin in people who are co-infected with genotype 1 hepatitis C virus and human immunodeficiency virus (HIV). Data showed 74 percent (28/38) of patients who were treated with INCIVEK (in-SEE-veck) combination therapy had undetectable hepatitis C virus (HCV RNA) 12 weeks after the end of all study treatment (SVR12) compared to 45 percent (10/22) who were treated with pegylated-interferon and ribavirin alone. INCIVEK was well tolerated with commonly used Atripla^®- and Reyataz^®-based HIV treatment regimens. Changes in CD4 counts were similar between the treatment groups and no HIV viral load breakthroughs were observed in either treatment group during the study. The most common adverse events in the INCIVEK arms of the study were fatigue, pruritis (itching), headache, nausea and rash. No cases of severe rash were reported and there were no discontinuations due to rash. Interim results from this study are being presented at the Conference on Retroviruses and Opportunistic Infections (CROI), March 5 to 8, 2012 in Seattle.
"Hepatitis C generally progresses faster, leads to more long-term liver complications and has been harder to cure among people who also have HIV," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "These new INCIVEK data are important as we work toward our goal of helping cure more people with hepatitis C. We're actively enrolling co-infected patients in a Phase 3 study and expect that data from this study will be included in a submission for a supplemental approval of INCIVEK."
The Phase 2 study includes two parts: Part A is evaluating people who are not currently being treated with antiretroviral therapy (ART) for HIV infection and Part B is evaluating those who are taking an Atripla- or Reyataz-based regimen for HIV. This study enrolled patients who were new to hepatitis C treatment (treatment naïve). Patients who were randomized to receive INCIVEK were treated with 12 weeks of INCIVEK, pegylated-interferon and ribavirin, followed by 36 weeks of pegylated-interferon and ribavirin alone. Interim data also showed that 68 percent (26/38) of patients treated with INCIVEK combination therapy in this study had a rapid viral response (RVR, undetectable hepatitis C virus at week 4 of treatment) compared to none (0/22) of the patients who received pegylated-interferon and ribavirin alone.
"There is a great need for treatments that are well tolerated and offer co-infected patients a better chance at a cure for hepatitis C while maintaining suppression of their HIV," said Douglas Dieterich, M.D., Professor of Medicine in the Division of Liver Diseases, Mount Sinai School of Medicine, New York City. "It's very encouraging that nearly three out of four people had undetectable hepatitis C virus 12 weeks after stopping INCIVEK combination therapy and that their HIV medicines continued to work during treatment."
Interim Study Results
Sixty-two people 18 and older were enrolled in this Phase 2 study and 60 received at least one dose of study drug. This analysis was conducted 12 weeks after patients completed all treatment. The ART regimens evaluated in this study were selected based on current HIV treatment guidelines from the U.S. Department of Health and Human Services, International AIDS Society and drug-drug interaction studies of INCIVEK with commonly used ART medicines.

(Click on table to enlarge)

The majority of adverse events in this study were mild or moderate. Adverse events that occurred more frequently in the INCIVEK arms compared to placebo (≥10 percent difference) were pruritis (itching), headache, nausea, rash, fever, and depression. Three patients, all in Arm B, discontinued all study treatment due to adverse events (one each due to gall stones, hemolytic anemia and nausea/vomiting).
About this Phase 2 Study
Vertex and its collaborator Janssen conducted extensive drug-drug interaction studies with INCIVEK and commonly used HIV medicines prior to initiating a development program in people co-infected with hepatitis C (HCV) and HIV. This Phase 2 study is a two-part (A and B), randomized, double-blind, placebo-controlled, parallel group, multi-center study in people chronically infected with both HCV and HIV who were new to HCV treatment. The primary endpoint of the study is to evaluate the safety and tolerability of INCIVEK combination therapy in people co-infected with HCV and HIV. A secondary endpoint is to evaluate rates of sustained viral response (SVR) 12 and 24 weeks after the end of treatment. The study is being conducted by Vertex in collaboration with Janssen.
Phase 3 Study Actively Enrolling
Enrollment is ongoing in a Phase 3 study evaluating 24- and 48-week response-guided regimens of INCIVEK combination therapy in people co-infected with HCV and HIV. Patients who are either new to treatment for HCV, or who had relapsed after at least one prior course of therapy with pegylated-interferon and ribavirin alone, will receive 24 or 48 weeks of INCIVEK combination treatment, based on their antiviral response. Patients who had not responded to a prior course of treatment (partial responders and nulls) will receive 48 weeks of INCIVEK combination treatment. A similar study is also being initiated by Janssen in its territories.
Data from In Vitro Evaluation of INCIVEK and HIV Protease Inhibitors
Also being presented at CROI this week are data from an in vitro evaluation of the anti-HIV activity of four HIV protease inhibitors (amprenavir, darunavir, lopinavir and atazanavir) in combination with INCIVEK. In the study, no antagonistic effects on the antiviral activity were observed when INCIVEK was used in combination with amprenavir, darunavir, and lopinavir, and slight antagonistic effects were observed on the antiviral activity of atazanavir.
About INCIVEK
INCIVEK^® (telaprevir) tablets is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK is the most prescribed direct-acting antiviral for the treatment of adults with genotype 1 chronic hepatitis C and has been used to treat more than 30,000 people in the United States.
INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for use in combination with pegylated-interferon and ribavirin for people with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously with interferon-based treatment but who did not achieve a sustained viral response, or viral cure (relapsers, partial responders and null responders).
Vertex developed telaprevir in collaboration with Janssen and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Janssen has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO^® in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and is known as Telavic^®.
INCIVEK^® is a registered trademark of Vertex Pharmaceuticals Incorporated.
PEGASYS^® and COPEGUS^® are registered trademarks of Hoffmann-La Roche.
Reyataz^® is a registered trademark of Bristol-Myers Squibb.
Atripla^® is a registered trademark of Bristol-Myers Squibb and Gilead Sciences, LLC.
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.¹ Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.¹ Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.¹
Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.² However, approximately 60 percent of people do not achieve SVR,^3,4,5 or viral cure,⁶ after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.^7,8
More than 170 million people worldwide are chronically infected with hepatitis C.⁶ In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.⁹Hepatitis C is four times more prevalent in the United States compared to HIV.⁹ The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.¹⁰ Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.^11,12 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.⁹
About Hepatitis C and HIV Co-Infection
There are 1 million people living with HIV in the United States,and an estimated 300,000 people living with HIV/AIDS in the United States are also infected with hepatitis C. ¹³ There have been dramatic improvements in the treatment of HIV and the prognosis for people living with HIV. However, liver disease progresses more rapidly in people co-infected with hepatitis C and HIV, with an increased rate of progression to cirrhosis, decompensated liver disease, hepatocellular carcinoma and death.^{14, 15, 16, 17} The hepatitis C cure rate with a 48-week treatment of pegylated-interferon and ribavirin, the current standard of care for people with co-infection, is approximately 29 percent.¹⁸
About Vertex
Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis, epilepsy and other life-threatening diseases.
Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and Science magazine named Vertex number one on its 2011 list of Top Employers in the life sciences.
Vertex's press releases are available at www.vrtx.com.
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including Dr. Kauffman's statements in the second paragraph of this press release and statements regarding ongoing and planned Phase 3 studies of INCIVEK combination therapy in people co-infected with HCV and HIV. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the outcomes from future clinical trials of INCIVEK combination therapy in co-infected patients may not be favorable and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
IMPORTANT SAFETY INFORMATION
Indication
INCIVEK^® (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.
Important Safety Information
INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines. Hormonal forms of birth control, including birth control pills, vaginal rings, implants or injections, may not work during treatment with INCIVEK.
INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.
INCIVEK can cause serious side effects including skin reactions, rash and anemia that can be severe. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.
Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com.
(VRTX-GEN)
References:
¹ Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed February 22, 2012.
² Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.
³ Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
⁴ Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
⁵ McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
⁶ Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
⁷ Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
⁸ Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
⁹ Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed February 22, 2012.
¹⁰ Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. Available at: http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. Accessed February 22, 2012. This report was commissioned by Vertex Pharmaceuticals, Inc.
¹¹ Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
¹² Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.
¹³ HIV Advocate. HIV/HCV Coinfection. Available at: http://www.hcvadvocate.org/hepatitis/factsheets_pdf/HIV_HCV20coinfecton_10.pdf. Accessed February 28, 2012.
¹⁴ Martin-Carbonero L, Benhamou Y, Puoti M, Berenguer J, Mallolas J, Quereda C, et al. Incidence and predictors of severe liver fibrosis in human immunodeficiency virus-infected patients with chronic hepatitis C: a European collaborative study. CID 2004;38:128-33.
¹⁵ Martinez-Sierra C, Arizcorreta A, Diaz F, Roldan R, Martin-Herrera M, Perez- Guzman E, et al. Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus. CID 2003;36:491-8.
¹⁶ Matthews GV, Dore GJ. HIV and hepatitis C coinfection. JGH. 2008; 23: 1000-1008.
¹⁷ Bruno R, Sacchi P, Puoti M, Soriano V, Filice G. HCV chronic hepatitis in patients with HIV: clinical management issues Am J Gastroenterol 2001; 97:1598—1606.
¹⁸ Levin, J. Pegasys/RBV in APRICOT Study- Adherence Improves SVR 300% in genotype 1. Available at: http://www.natap.org/2005/ICAAC/icaac_31.htmAccessed February 28, 2012.
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March 5, 2012

DO YOU KNOW A HERO? I DO!

DO YOU KNOW A HERO? I DO!
By Kathie Beach
In 1988, my husband Kurt, a Smithfield Police Officer, responded to an emergency call and tried to save a child's life who had been born with spina bifida and had a trachometry in her throat to be able to breathe. On this day, the child was not breathing and her heart had stopped. Kurt proceeded mouth to trach breaths and CPR on her having to suck the blood and mucous out of the airwaves to try to give her oxygen. It was to no avail, the child, sadly died. The mother of that precious child knew Kurt did everything within his power to save her. She considers Kurt a hero. So do I.
In 1988 the police department was not trained on blood pathogens and Hepatitis C had not even been classified yet, being called Non A and Non B Hepatitis. Kurt's attempt to save a life put his life in jeopardy. Later, he found out the terrible news that he had contracted this disease when he came in contact with the child's infected blood due to multiple blood transfusions her condition had demanded.
All these years God has kept His hand on Kurt. Although he was diagnosed with Hepatitis C and aggressive chronic liver disease, he was able to work and go about his life. He worked hard and gave tirelessly of whatever was required of him. He endured countless tests, procedures and experimental therapies to try to rid his body of the disease. The doctors were amazed by his stamina, his faith and his encouraging ways. He bounced back again and again and I suppose we always thought he would. Then in May of this year he ended up at Obici hospital for a five day stay. From there he went to MCV where his team of doctors did extensive tests and evaluations. Another stay at Obici and another round at MCV and then finally this week we are told by his team of doctors that Kurt needs a new liver and we need to prepare him for a live donor as a wait for a DD (deceased donor) is in the 100,000s. They did not mince words that Kurt could die waiting for a liver donor.
Kurt needs a living donor liver transplant.
This is a procedure that involves the removal of the recipient's (Kurt) native liver and replacing it with a potion of the living donor's liver. Both Kurt's and the donor's livers will regenerate to normal functional volume within weeks. AMAZING!
Kurt has a wonderful team of doctors who have monitored him over the years and when they convened they said he is a perfect candidate for this operation. The doctor went so far as to say 'Kurt, you will feel like a new man. Able to work, play and live and you will feel better than you have in years.'
My hero needs a hero, he needs a living donor.
(Just to clarify...this was an email petition sent out to friends and family in 2008. Kurt received a living liver donor in 2009 after 3 failed deceased donor attempts.)

Treatment of chronic hepatitis C genotype 1 with triple therapy comprising telaprevir or boceprevir

Review article | Published 24 February 2012, doi:10.4414/smw.2012.13516
Cite this as: Swiss Med Wkly. 2012;142:w13516

Swiss Association for the Study of the Liver¹

¹ Current Council Members of the Swiss Association for the Study of the Liver are listed in www.sasl.ch.

Abbreviations: AASLD, American Association for the Study of Liver Diseases; BOC, boceprevir; CHC, chronic hepatitis C; EASL, European Association for the Study of the Liver; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HIV, human immunodeficiency virus; PEG-IFN-α, pegylated interferon-α; RBV, ribavirin; SVR, sustained virological response; SASL, Swiss Association for the Study of the Liver; TPV, telaprevir.

Summary

Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. Two first-generation protease inhibitors, telaprevir and boceprevir, have recently been approved for the treatment of chronic hepatitis C genotype 1. Triple therapy comprising pegylated interferon-α, ribavirin and telaprevir or boceprevir increases sustained virological response rates to ~70% and allows to shorten treatment duration in ~½ of treatment-naïve patients with chronic hepatitis C genotype 1. Sustained virological response rates in treatment-experienced patients depend on the response to previous treatment, ranging from >80% in previous relapsers to ~30% in previous null responders. These advances come at the expense of new adverse effects and increased cost. In addition, treatment of chronic hepatitis C will become more complex. In these times of changing medical practice, the present expert opinion statement by the Swiss Association for the Study of the Liver shall provide guidance on the treatment of chronic hepatitis C with triple therapy comprising telaprevir or boceprevir.

Key words: boceprevir; chronic hepatitis C; HCV; hepatitis C virus; interferon; protease inhibitor; ribavirin; telaprevir

Introduction

Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) [1–3]. An estimated 120–200 million individuals worldwide and about 1% of the general population in Switzerland are chronically infected with HCV. About 50% of the chronic HCV infections in Switzerland are due to genotype 1 [4]. While the incidence of acute hepatitis C has declined significantly since the introduction of anti-HCV screening of blood and blood products in 1990, the number of patients presenting with decompensated cirrhosis and HCC is expected to increase further, attaining a peak around 2020 [1, 5]. More than 50% of the individuals at risk may currently be unaware of their infection. Strategies to increase testing and detection rates are currently being explored (e.g., screening of populations at risk vs. birth cohort screening) [6, 7].

Fifty to 80% of acutely infected individuals develop persistent infection. Of these, 2–20% will develop liver cirrhosis within the first 20 years, and accumulating evidence suggests that disease progression may increase in a nonlinear fashion thereafter [8]. Once cirrhosis is established, the rate of HCC development is 1–6% per year. Factors associated with more frequent and rapid progression to cirrhosis are, among others, higher age at the time of infection, male sex, alcohol consumption, coinfections with the human immunodeficiency virus (HIV) or hepatitis B virus (HBV), nonalcoholic fatty liver disease and smoking. Comprehensive management of chronic hepatitis C (CHC) takes these factors into consideration and aims at improving the ones that can be modified (alcohol abstinence; weight loss, regular physical activity and other measures to control the metabolic syndrome; vaccination against HBV [and hepatitis A virus]; smoking cessation including cannabis) [9].

While non-invasive methods for fibrosis assessment are actively being pursued [10], liver biopsy remains the reference for grading and staging of CHC. The Metavir and Ishak scoring systems are most often applied. Fibrosis stages are classified from 0 (absence of fibrosis) to 4 (cirrhosis) in the Metavir system [11], and from 0 to 6 in the Ishak system [12].

The decision to treat CHC is based on the analysis of numerous variables and should take into account the specific situation of each patient. Treatment is clearly recommended for patients with Metavir fibrosis stage ≥2 who do not have any contraindications. For other patients, decisions will have to be made on an individual basis. Additional factors that come into consideration are, among others, the (biological) age and general condition of the patient, the patient’s personal and professional plans, the duration of HCV infection, the risk of developing cirrhosis, the likelihood of response to therapy, and comorbidity.

For the last 10 years, standard therapy of CHC consisted of pegylated interferon-α (PEG-IFN-α) combined with ribavirin (RBV) for (16-)24-48(-72) weeks, yielding sustained virological response (SVR) rates of 40–50% in patients infected with HCV genotype 1 and ~80% in patients infected with genotypes 2 and 3. Definitions of virological response patterns are provided in table 1.

Polymorphisms near the IL28B gene have recently been identified as strong predictors of the outcome of IFN-α-based antiviral therapy (reviewed in [13, 14]). A number of laboratories offer IL28B genetic testing, but its role in clinical practice and decision making, if any, remains to be defined.

A first generation of directly acting antivirals, the NS3-4A protease inhibitors telaprevir (TPV; Incivo^®) and boceprevir (BOC; Victrelis^®), has recently been approved for the treatment of CHC genotype 1. TPV and BOC have to be combined with PEG-IFN-α and RBV in order to avoid the rapid selection of HCV strains resistant to antiviral therapy [15, 16]. Triple therapy comprising TPV or BOC increases SVR rates to ~70% in treatment-naïve patients with CHC genotype 1 [17–19]. In treatment-experienced patients, SVR rates depend on the virological response to previous therapy with PEG-IFN-α and RBV, ranging from >80% in patients with previous relapse to ~50% in patients with previous partial response and ~30% in patients with previous null response [20–22]. Treatment schedules comprising TPV or BOC have more side effects than PEG-IFN-α and RBV, and should be managed carefully.

A significant increase in the number of patients with CHC to be treated is expected for 2012, with triple therapy regimens that are more complex, as discussed below [23]. These expected developments represent a significant challenge and will stretch current resources.

The present Swiss Association for the Study of the Liver (SASL) expert opinion statement is not intended as guideline but shall provide some guidance on the management of CHC genotype 1 and the use of TPV and BOC. It is based on the results of recently published phase III clinical trials performed in treatment-naïve and treatment-experienced patients (ADVANCE [17], ILLUMINATE [19] and REALIZE [20] for TPV as well as SPRINT-2 [18], RESPOND-2 [21] and PROVIDE [22] for BOC), and take into account the recently updated American Association for the Study of Liver Diseases (AASLD) Practice Guidelines [3] as well as the labels approved by the US Food and Drug Administration, the European Medicinal Agency, and Swissmedic. Current European Association for the Study of the Liver (EASL) Clinical Practice Guidelines [2] are expected to be updated shortly. In addition, different national guidelines are in preparation. Therefore, as recommendations are emerging and as real-life data and practical experience on the use of TPV and BOC are still limited, it is strongly recommended to initiate and pursue triple therapy comprising TPV or BOC only in close collaboration with an expert centre.

Click to enlarge

Practical use of telaprevir and boceprevir

TPV is available in the form of 375-mg film-coated tablets and has to be taken at a dose of 750 mg every 8 hours (i.e., two tablets every 8 hours), with a meal or a snack containing ~20 g of fat to increase bioavailability. BOC is available in the form of 200-mg capsules and has to be taken at a dose of 800 mg every 8 hours (i.e., 4 capsules every 8 hours), with a meal or a snack. Dosing every 8 ± 1 hour rather than 3 times per day is important to maintain inhibitory drug serum concentrations and to avoid antiviral resistance development. TPV and BOC should never be used alone, and doses should never be reduced. When used alone, these drugs will not be effective and will cause emergence of HCV strains with resistance to antiviral therapy that could be difficult to treat subsequently. RBV can be taken with the first dose of TPV or BOC in the morning and with the last dose of TPV or BOC in the evening.

TPV and BOC are only approved for use in patients with HCV genotype 1 infection. The development of antiviral resistance is more frequent in subtype 1a than 1b but this should not influence therapeutic decision making.

Both TPV and BOC have a strong potential for drug-drug interactions, as they affect the metabolism of other drugs metabolised through cytochrome P450 3A4 (CYP3A4) and other pathways [24]. See package inserts, continuously updated online databases (e.g., http://www.hep-druginteractions.org, Epocrates, Medscape) and Leise et al. [25] for known drug-drug interactions and contraindicated drugs. Commonly used drugs that are contraindicated in combination with TPV or BOC include, among others, atorvastatin, lovastatin, simvastatin, sildenafil, alfuzosin, carbamazepin, phenytoin, oral midazolam, and St. John’s wort. Among the drugs commonly used to manage adverse effects of therapy, paracetamol and metoclopramide (but not domperidone) are allowed. TPV and BOC may decrease citalopram levels and efficacy.

Main adverse effects of TPV include anemia, nausea and diarrhea, skin rashes and pruritus as well as anorectal disorders. Rash should be managed in collaboration with an experienced dermatologist and should follow recommendations that have recently been summarised [26]. TPV has to be discontinued if rash progresses and becomes severe. Rare cases of DRESS (drug-related eosinophilia with systemic symptoms) and Stevens Johnson syndrome/toxic epidermal necrolysis have been observed. If either one is suspected, all drugs have to be stopped immediately, followed by emergency dermatological consultation.

Main adverse effects of BOC include anemia, with a significant number of patients requiring concomitant erythropoietin treatment in phase II and III clinical trials, as well as dysgeusia.

Anemia can develop rapidly and become very pronounced with both TPV and BOC, especially in patients with cirrhosis. Therefore, close monitoring is recommended. Anemia should be managed by timely RBV dose reduction and, if needed, blood transfusions and/or erythropoetin.

Data on the safety and efficacy of TPV and BOC in patients with HIV coinfection are emerging. TPV and BOC should be used only in close collaboration with an expert in these patients.

There is no data in liver transplant recipients, hemodialysis patients and children, and the use of TPV and BOC in these situations is currently proscribed.

In registration trials, TPV was used with PEG-IFN-α2a 180 µg per week plus RBV 1000–1200 mg per day and BOC was used with PEG-IFN-α2b 1.5 µg/kg per week plus RBV 600–1400 mg per day. However, both forms of PEG-IFN-α may be used with RBV and either TPV or BOC.

PEG-IFN-α is contraindicated in decompensated cirrhosis.

Strict contraception must be followed during and for 6 months after the end of triple therapy because of the potential teratogenicity of RBV.

Who should be treated with triple therapy comprising TPV or BOC?

Triple therapy will represent a new standard for most treatment-naïve patients with CHC genotype 1 as well as treatment-experienced patients with a relapse or partial response to previous therapy with PEG-IFN-α and RBV (table 2).

Treatment of CHC is expected to change significantly within the next few years, with the arrival of better tolerated and even more efficacious new drugs as well as the advent of IFN-free/sparing regimens [27–30]. These developments shall significantly improve the outlook for our patients. Therefore, deferring treatment may be considered in patients who’s treatment can be safely postponed.

Treatment-naïve patients with favourable baseline predictors (HCV RNA <4 x 10⁵ IU/ml, absence of advanced fibrosis or cirrhosis) who achieve a rapid virological response (RVR; see table 1) have excellent chances to achieve SVR with 24 weeks of therapy with PEG-IFN-α and RBV alone [31]. Therefore, a 4-week lead-in with PEG-IFN-α and RBV may be considered in patients with the above-mentioned favourable baseline predictors and treatment continued without adding TPV or BOC for a total of 24 weeks in those who achieve RVR.

Lead-in with PEG-IFN-α and RBV may also be considered if there are doubts concerning the tolerance or adherence to PEG-IFN-α and RBV backbone therapy.

There is currently only limited data on the use of BOC in patients with previous null response. In general, retreatment of previous null responders has to be considered carefully, as SVR rates remain limited, especially in patients with cirrhosis. Inclusion of such patients into clinical trials involving quadruple therapy or IFN-sparing regimens may be considered. Lead-in with PEG-IFN-α and RBV may be considered in previous null responders, especially in cirrhotics, with the addition of TPV or BOC only in case of ≥1 log decline of HCV RNA at week 4. Subanalysis of the REALIZE trial revealed that 54% of the patients with ≥1 log decline after 4 weeks of lead-in with PEG-IFN-α and RBV achieved SVR with triple therapy comprising TPV, compared to only 15% of those with a decline of HCV RNA <1 log [32].

Careful monitoring and stopping rules, as detailed below, shall reduce the risk of selecting HCV strains resistant to antiviral therapy. While long-term consequences of the selection of such strains are presently unknown, antiviral resistance is likely to affect future treatment options [15, 16].

Figure 1 Telaprevir-based triple therapy. (A) Treatment-naïve patients with CHC genotype 1 and treatment-experienced patients with previous relapse. (B) Treatment-experienced patients with CHC genotype 1 and previous partial or null response. eRVR, extended rapid virological response (see table 1 for definitions of virological response patterns); P, pegylated interferon-α; R, ribavirin; T, telaprevir; wks, weeks.

Figure 2 Boceprevir-based triple therapy. (A) Treatment-naïve patients with CHC of genotype 1 without cirrhosis. (B) Treatment-experienced patients with CHC genotype 1 and previous relapse or partial response without cirrhosis. (C) All cirrhotic patients and prior null responders. B, boceprevir; BPR = B + P + R; P, pegylated interferon-α; R, ribavirin; RVR8, rapid virological response at week 8 (see table 1 for definitions of virological response patterns); wks, weeks.

Click to enlarge

Specific treatment algorithms

Telaprevir-based triple therapy

• Treatment-naïve patients and previous relapsers with CHC genotype 1 (fig. 1A)

Non-cirrhotic patients who achieve eRVR

12 weeks TPV + PEG-IFN-α + RBV

+ 12 weeks PEG-IFN-α + RBV

Non-cirrhotic patients who do not achieve eRVR and all cirrhotic patients

12 weeks TPV + PEG-IFN-α + RBV

+ 36 weeks PEG-IFN-α + RBV

• Previous partial and null responders with CHC genotype 1 (fig. 1B)

12 weeks TPV + PEG-IFN-α + RBV
+ 36 weeks PEG-IFN-α + RBV

Lead-in with PEG-IFN-α and RBV may be considered in previous null responders, especially in cirrhotics, with the addition of TPV only in case of ≥1 log decline of HCV RNA at week 4.

Stopping rules:

Stop all therapy if HCV RNA >1000 IU/ml at either week 4 or 12 of triple therapy.
Stop all therapy if HCV RNA detectable at wk 24.
Stop all therapy if previously negative HCV RNA becomes confirmed positive again under treatment.

Boceprevir-based triple therapy

• Treatment-naïve patients with CHC genotype 1 (fig. 2A and 2C)

Non-cirrhotic patients who achieve RVR8