This blog is all about current FDA approved drugs to treat the hepatitis C virus (HCV) with a focus on treating HCV according to genotype, using information extracted from peer-reviewed journals, liver meetings/conferences, and interactive learning activities.
Risk Of Developing Liver Cancer After HCV Treatment
I'm off to take my mother out to lunch, a weekend treat I so look forward to. If you have an elderly parent living alone, don't send them flowers, send yourself instead.
Today on the blog is short video on treating hepatitis C, and few updates from NATAP. This invaluable website has been in existence since 1997, thank you executive director Mr. Jules Levin for continuing to advocate for all people living with HIV/AIDS and HCV, you are sincerely appreciated.
Lastly, an alarming article discussing the difficulty hospitals have sterilizing intricate surgical instruments. The article points out that officials don't know how often dirty instruments are the cause of hospital-acquired infections. Dr. Melissa Schaefer from the CDC remarked the cases of hospital infections they hear about are only the tip of the iceberg. Also a few entries from my favorite stem cell blog,and an article from spoonful of medicine, which is a blog from the scientific journal Nature.
Filthy Surgical Instruments: The Hidden Threat In America’s Operating Rooms
By Joe Eaton
Source: NJTODAY.net
It seemed simple enough at the time. In 2009, John Harrison, a 63–year-old oil industry sales manager in Mission, Texas, had surgery to repair the rotator cuff in his right shoulder, a routine procedure that usually requires at most a single night’s stay in the hospital, followed by physical therapy. For Harrison, however, there was nothing routine about the ordeal that ensued.
In the weeks following the surgery, his scar turned bright red, hot to the touch, and oozed thick fluid that looked “like butter squeezed from a bag.” Alarmed, Harrison’s wife, Laura, called The Methodist Hospital in Houston, where the surgery was performed. The doctor urged Harrison to immediately make the seven-hour drive back to Houston for an emergency checkup.
A larger problem
Was the Methodist case a fluke? Hardly. Filthy, dangerous medical implements have been showing up in hospitals and outpatient surgery centers with alarming regularity. In 2009, the Department of Veterans Affairs admitted that 10,737 veterans in Florida, Tennessee and Georgia were given endoscopies or colonoscopies between 2002 and 2009 with endoscopes that may have been improperly cleaned. Some of those patients later tested positive for HIV, hepatitis C, or hepatitis B. Several lawsuits filed against the VA by veterans are currently working their way through the courts, and attorneys expect many others to follow. Investigation of a 2008 hepatitis C outbreak that sickened at least six people in Las Vegas revealed that an outpatient surgery center was improperly cleaning endoscopes and reusing biopsy forceps designed for a single use. Following that outbreak, a Centers for Medicare and Medicaid Services (CMS) pilot program inspected 1500 outpatient surgery centers and cited 28 percent for infection control deficiencies related to equipment cleaning and sterilization.
Charles Hancock, an independent medical device sterilization consultant in New York who has worked in the industry since the 1960s, said some central sterile departments are clean and efficient, while others are dirty and overcrowded with a “dungeon mentality.” Most, he said, are somewhere in the middle.
If someone is not in a war, but someone else declares war on them or actually attacks them, I would say the reality is that war has started and there are two opposing sides.
However, has that happened when it comes to stem cells?
I’m by no means the only one who blogs about stem cells, but it is just that professors still are reluctant in the stem cell field to blog. Two outstanding blogs that tied for first place in my 2011 stem cell awards are the Stem Cell Network of Canada and Stem Cell Assays, by Drs. Gunn and Bersenev. As I said in my awards post, also worth noting is the CIRM Research Blog by the super Amy Adams, the winner of our 2010 Blog of the Year Award and the California Stem Cell Report by David Jensen, who is focused on CIRM predominantly.
Companies these days use crowdsourcing for everything from striking gold to marketing facial moisturizer. Now a new startup, Transparency Life Sciences, hopes to harness that collaborative power to make clinical trials more effective and efficient by asking the opinions of doctors as well as patients and their families. The company, launched last month and based in New York, is the latest in a string of so-called ‘open innovation’ drug development initiatives. But until now most of these efforts have only crowdsourced from a limited group: researchers.
Back in 2009 Indiana-based Eli Lilly launched its Open Innovation Drug Discovery program, an online platform for researchers to submit small molecules for drug screening. “The goal of this kind of program is to attract researchers with new molecules and ideas in an unbiased way,” says Alan Palkowitz, vice president of discovery chemistry research and technologies at Eli Lilly.
Other big pharmaceutical companies have also established a handful of open innovation platforms for preclinical drug development. New York-based Pfizer has been building partnerships with institutions through its Centers for Therapeutic Innovation program since 2010, and Britain’s GlaxoSmithKline funds the non-profit open innovation organization Tres Cantos Open Lab Foundation. Most recently, in October, the United Nations World Intellectual Property Organization partnered with seven major drug companies in an intellectual property sharing consortium targeting neglected tropical diseases.
As the week comes to a close, I celebrate the national focus placed on hepatitis C this week. The last few days of awareness was first generated when research resulted in the devastating headlines that "Hepatitis C Now Kills More Americans Than HIV "
The research has given rise to many new articles on HCV, thank goodness. The CDC took part in the Q&A article @ Time Healthland discussing risk, transmission and treatment.
Healthland spoke with Dr. John Ward, who heads the CDC’s effort to fight hepatitis C, about who is at risk of infection, how the disease is really spread and why it’s important to know your hepatitis C status now.
The author Lucinda K. Porter, RN, may sound familiar to the HCV community, she has written for HCV Advocate since 1998. Over the years, many HCV patients have gained invaluable information by reading Ms. Porters HealthWise columns published in the sites monthly newsletters. This December the authors new book "Free from Hepatitis C: Your Complete Guide to Healing Hepatitis C" was published. The book is a must read for the newly diagnosed, or anyone living with hepatitis C. I am honored to point my readers to a new review of Ms. Porters book at Xpress Reviews, please check out the review here, and if interested click here to order "Free from Hepatitis C: Your Complete Guide to Healing Hepatitis C." priced at $11.77.
Most Popular Articles On The Blog And Website This Week
In The News
Hepatitis C, a leading killer, is frequently undiagnosed but often curable February 24, 2012
By Jeffrey Norris Source
(Medical Xpress) -- Hepatitis C virus — not AIDS-causing HIV — is the leading chronic virus infection leading to death in the United States, and its victims most often are baby boomers. More than half who are infected do not know it.
Researchers from the U.S. Centers for Disease Control and Prevention (CDC) found in a study published in the February 21 issue of the Annals of Internal Medicine that hepatitis C had overtaken HIV as a cause of death in the United States by 2007.
Deaths in the United States due to HIV infection have been steadily decreasing, and dropped below 13,000 in 2007, while deaths from hepatitis C infection have been steadily increasing, first surpassing 15,000 per year in 2007.
The good news, according to UCSF liver specialist Alex Monto, MD, is that there has been progress in fighting both diseases, and the kinds of drug combination strategies that have done so much to transform HIV infection from a death sentence to a manageable disease are poised to further boost cure rates for those infected with hepatitis C.
“We know that not enough people with risk factors get tested,” Monto says. “There are a lot of people walking around with hepatitis C who don’t know it.”
Monto directs the liver clinic at the UCSF-affiliated San Francisco Veteran’s Affairs Medical Center, one of four hepatitis C centers nationally within the VA system. Like boomers, veterans are disproportionately affected by hepatitis C. The VA cares for 165,000 patients who are chronically infected with the virus.
Three Million in U.S. Diagnosed with Hep C
Chronic Hepatitis C has been diagnosed in about three million people in the United States. It often causes no symptoms, and many who have been infected for years or even decades may remain unaware of it until symptoms finally appear. The ultimate cause of death attributable to chronic infection is cirrhosis or liver cancer, although the disease progresses to cirrhosis in fewer than half of cases. There is no vaccine.
“The main risk factor in the United States is past injection-drug use,” Monto says. “The others most at risk are those who received blood transfusions before 1992,” Monto says, referring to the year when high-quality screening of the blood supply was implemented.
Compared to HIV or hepatitis B, the risk of hepatitis C being transmitted by sex is low, Monto says, but among men who have sex with men there has been an increase in reports of the virus being sexually transmitted, more so among those who are infected with HIV.
“Anybody with a history of ever being exposed to injection drugs or who received a transfusion before the blood supply was screened should be tested,” Monto says. “That’s not controversial at all. What has been controversial is whether or not all baby boomers should be screened.”
Another study in this week’s edition of the journal suggests that a one-time blood test ordered by primary care providers to screen for antibodies to hepatitis C in those born between 1945 and 1965 would be cost effective — costing $2,874 for each chronically infected patient identified — and would lead to the identification of more than 800,000 previously undiagnosed cases.
Those who are chronically infected may be able to reduce the likelihood of disease progression by avoiding alcohol, by maintaining a healthy weight, and by being vaccinated against hepatitis A and hepatitis B, Monto says.
Treatment Often Cures Hepatitis C
About four out of five who are infected do not rid themselves of the virus without treatment. For about a decade the standard treatment was a combination of two drugs — pegylated interferon given once per week by subcutaneous injection, and daily ribavirin pills, with treatment lasting from six to 11 months. This treatment represented a vast improvement — offering cure rates of 40 percent to 50 percent in most patients, according to Monto.
Within the past year two new drugs of a type known as protease inhibitors have become available. These are valuable for the 75 percent of U.S. hepatitis C patients infected with a form of the virus called genotype 1. With the protease inhibitors added to the mix, the duration of treatment may be shorter, and the cure rate has increased to about 70 percent in patients who have not previously been treated, Monto says. A cure may be less likely for those who have been previously treated, depending on how they responded to earlier treatment.
“New therapies are clearly getting better, and there are probably 25 to 30 new drugs in the pipeline, with many coming out in the next few years,” Monto says. “There are going to be drugs that are better than the ones we have so far.” Several UCSF researchers, including Monto, are helping to evaluate new drugs in clinical trials. UCSF researchers also are investigating the role of the immune system in hepatitis C and hepatitis B infection.
Not to Be Confused with Hepatitis B
Hepatitis B chronically infects about half as many as hepatitis C in the United States, and hits those of Asian descent especially hard — they account for half of hepatitis B infections. Hepatitis B is responsible for about 1,800 deaths yearly in the United States.
Despite the similar names, the two viruses are not closely related. Hepatitis B is spread much more easily through sexual intercourse, and passes from mother to newborn child much more easily. In most adults who become infected the immune system successfully controls infection. Only about five percent of adults exposed to hepatitis B become chronically infected, according to Monto.
There are vaccines for hepatitis B. A UCSF laboratory team led by William Rutter, PhD, now professor emeritus, first demonstrated that an uncontaminated source of material for a hepatitis B vaccine could be obtained by mass-producing viral proteins in genetically engineered, laboratory-grown yeast. This was the groundwork leading to the first marketed genetically engineered vaccine, made by Chiron, a company co-founded by Rutter.
Provided by University of California, San Francisco (news : web)
Big Pharma
Idenix Pharmaceuticals Reports Fourth Quarter and Year End 2011 Financial Results and Provides Pipeline Update
CAMBRIDGE, Mass., Feb. 23, 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 reported unaudited financial results for the fourth quarter and year ended December 31, 2011 as well as the advancement of its hepatitis C virus (HCV) development pipeline.
Operational Highlights
IDX184 Program
The Company's lead program, IDX184, is a pan-genotypic oral nucleotide polymerase inhibitor for the treatment of HCV. In July 2011, Idenix initiated enrollment of treatment-naive HCV-infected patients into a 12-week phase IIb clinical trial of IDX184 in combination with pegylated interferon and ribavirin. In January 2012, the Company reported an interim analysis from this study of the first 31 patients who completed 28 days of treatment demonstrating favorable safety and antiviral activity. At 12 weeks, the Complete Early Virologic Response (cEVR < 25 IU/mL) was 93% for the 100 mg IDX184 arm (n=15) and 81% for the 50 mg IDX184 arm (n=16) of the study (intent-to-treat analysis). The side effect profile of the combined therapy has remained consistent with the known safety profile for pegylated interferon and ribavirin.
In February 2012, the U.S. Food and Drug Administration removed the partial clinical hold on IDX184 after review of the interim phase IIb data and the independent Data Safety Monitoring Board's recommendation to continue the study. The Company has now begun enrollment of an additional 30 patients under expanded enrollment criteria in the ongoing phase IIb clinical trial. Additionally, the Company anticipates implementing a broad phase IIb program with IDX184, focusing on the evaluation of interferon-free direct-acting antiviral (DAA) combination regimens, in the coming months.
IDX719 Program
In January 2012, the Company initiated a phase I clinical study of IDX719, its NS5A inhibitor candidate. The first part of the study is evaluating the safety, pharmacokinetics and food effect of IDX719 in 48 healthy volunteers at single doses ranging from 5 to 100 mg. Dosing up to 50 mg has been completed in healthy volunteers and to date IDX719 has been well tolerated. A cohort of eight HCV genotype 1-infected patients received single doses of IDX719 of either 1, 5, 10 or 25 mg (2 patients per dose). Mean maximal viral load reductions were 1.9 log(10), 2.6 log(10), 3.3 log(10) and 3.7 log(10), respectively. A 3-day proof-of-concept segment of the study in treatment-naive genotype 1 HCV-infected patients is expected to begin in the second quarter of 2012 with additional cohorts of genotype 2, 3, or 4 HCV-infected patients to be added during the study.
Nucleotide Discovery Program
In January 2012, Idenix selected two nucleotide inhibitors, IDX19368 and IDX19370, as potential clinical candidates from its novel nucleotide prodrug discovery program. IDX19368 has demonstrated strong potency in preclinical studies and as a result the Company has chosen IDX19368 as its lead candidate and expects to submit an investigational new drug application (IND) for IDX19368 in mid-2012. The Company continues to identify new promising compounds and evaluate multiple candidates for further development from this discovery program.
"Our focus for 2012 will be to build on the progress we made last year through the continued advancement of our pipeline of novel HCV drug candidates," said Ron Renaud, Idenix's President and Chief Executive Officer. "Now that the partial clinical hold has been removed for IDX184, we will be able to explore the full potential of this promising nucleotide polymerase inhibitor in combination with other DAAs in a broad phase IIb program. The early results are promising for IDX719, our NS5A inhibitor, in HCV patients and we look forward to completing the phase I clinical trial, as well as initiating a phase I study for our next-generation nucleotide inhibitor, IDX19368. We believe that the potent and pan-genotypic profiles of our drug candidates support their potential role in future HCV combination regimens."
Vertex Pharmaceuticals, some investors theorized in recent months, was about to be left in the dust by other companies with more effective drugs in development against hepatitis C. Today, Vertex released some clinical trial data which just might make some folks wait a minute before declaring this story to be “Game Over.”
The Cambridge, MA-based biotech company (NASDAQ: VRTX) today released some preliminary results from a study of 46 hepatitis C patients who got a combination of three oral pills—Vertex’s telaprevir (Incivek), its experimental drug VX-222, and standard ribavirin as their first form of treatment. The study found that 83 percent (38 of 46 patients) had undetectable amounts of the liver-damaging virus after 12 weeks of therapy on the three-pill combo regimen. While patients aren’t considered cured until 24 weeks have passed with undetectable amounts of the virus in the blood, past studies have shown that 12-week measurements are typically predictive of what researchers can expect to see at 24 weeks.
Shares of Vertex climbed 3.4 percent, to $38.90, in mid-day trading after the news.
The results are a small feather in Vertex’s cap, as it seeks to hold onto its market leadership position in hepatitis C, and improve upon the standard of care by eliminating the standard injectable interferon that causes flu-like side effects. Vertex won FDA approval last May for its market-leading protease inhibitor, telaprevir, which, when given with interferon and ribavirin, doubled the cure rate to about 80 percent of patients new to therapy. But competition in the field is fierce, as various companies are researching antiviral cocktails that include not just protease inhibitors, but also nucleotide polymerase inhibitors, and non-nucleotide polymerase inhibitors that attack the virus from different angles, and seek to raise the cure rate to near 100 percent, while getting rid of the dreaded interferon.
Gilead Sciences paid $11 billion last November to acquire Pharmasset and its portfolio of nucleotide
polymerase inhibitors that seek to establish a new standard of care, and Bristol-Myers Squibb countered in January with a $2.5 billion takeover of Inhibitex. But just six days ago, Gilead stock tumbled when it released preliminary data from a study that said six of eight patients who hadn’t responded to prior therapy, and then took its nucleotide polymerase inhibitor (GS-7977) along with ribavirin, ended up having relapses. That finding put a dent in the thesis that the Gilead drug would work on its own against virtually all genotypes of hepatitis C patients, even in tough patients who failed on prior therapies. Essentially, it created an opening for Vertex and other companies, as Gilead said in a statement that “additional direct acting antivirals may be necessary,” for the toughest patients to treat.
It’s too soon to say if Vertex’s combo will end up being the answer to Gilead, but if Vertex can follow through on this latest finding, and turn in an application for FDA approval of the new all-oral regimen by year-end 2014 or early 2015, that “would keep Vertex competitive in the emerging all-oral space for HCV,” said Jason Kantor, an analyst with RBC Capital Markets, in a note to clients today. He added a caveat that “the sustained viral response (SVR) data presented, however, is only from a small and select portion of the total patients treated, and future updates will be key to determining the real efficacy of this regimen.”
Side effects of the drug were mostly mild, and there were no cases of moderate to severe rash that has been seen in other studies of Vertex’s telaprevir when given in combination with interferon and ribavirin. Two patients with the genotype 1b form of the virus dropped out of the study because of adverse events, Vertex said. More data from this study, called Zenith, has been submitted for detailed presentation at a medical meeting in the first half of 2012, Vertex said.
Based on the encouraging antiviral response rates seen so far, Vertex plans to run a bigger Phase 2b study of this all-oral regimen of telaprevir, VX-222, and ribavirin among patients with the most common genotypes of the disease (1a and 1b), and who are new to treatment. That trial would be designed to lay the groundwork for a pivotal, Phase 3 trial that could serve as the basis for an FDA application for marketing, Vertex said.
Besides this combo, Vertex is testing other all-oral combinations, through molecules it obtained in a collaboration with South San Francisco-based Alios Biopharma. For more of the background on that deal and its strategic importance to Vertex’s position in the hepatitis C market, see this feature story from last month.
Luke Timmerman is the National Biotech Editor of Xconomy, and the Editor of Xconomy Seattle. E-mail him at ltimmerman@xconomy.com or follow him on Twitter at twitter.com/ldtimmerman.
Context: HCV infection is strongly associated with development of insulin resistance and type-2 diabetes, however molecular mechanism of these associations is not known. The aim of this review was to conduct a comprehensive literature search to understand the nature of the association between hepatitis C virus (HCV) infection and insulin resistance (IR). We also explored the role of HCV core protein and NS5a in modulating the course of the insulin-signaling pathway.
Evidence Acquisitions: We searched Directory of Open Access Journals (DOAJ) Google Scholar, Pubmed (NLM), LISTA (EBSCO), Web of Science (TS and PakMediNet).
Results: Emerging evidence suggests an association between HCV infection and carotid/coronary vascular disease. IR appears to be a dominant underlying cause of accelerated atherosclerosis in patients with chronic hepatitis C (CHC). HCV can induce IR directly through the stimulation of SOCS3 and PPA2, and both of these molecules have been shown to inhibit interferon-α signaling. Improvement of insulin sensitivity may increase the response rate to antiviral treatment and prevent IR complications, including vascular diseases. The results of several clinical trials that have used insulin sensitizers (metformin and PPAR-γ agonists) have been inconclusive.
Conclusions: Beside the association between HCV and IR, the published data also have showed the possible association of HCV core and NS5A protein with IR.
By: Ellie Merritt| NBC4i.com Published: February 24, 2012
There's a procedure many have never heard of but is being used to treat certain cancers with great success, especially liver cancer.
It's called transarterial chemoembolization and is often referred to as "chemo beads." It is a minimally invasive procedure that injects chemotherapy drugs directly into the blood vessel feeding the tumor.
It's called transarterial chemoembolization and is often referred to as "chemo beads." It is a minimally invasive procedure that injects chemotherapy drugs directly into the blood vessel feeding the tumor.
Melissa Palmer, MD is medical director of hepatology at NYU Hepatology Associates Plainview and is clinical professor of medicine at NYU. She graduated from Columbia University with a BA and was trained in hepatology (as well as medical school) at the Mount Sinai School of Medicine in New York City. Dr. Palmer is Board Certified in Gastroenterology and in Internal Medicine.
Vertex ($VRTX) today unveiled a slate of somewhat positive interim midstage results for an all-oral combo regimen that includes its game-changing drug Incivek along with the experimental VX-222--its non-nucleoside polymerase inhibitor--and ribavirin.
The standard goal for new hepatitis C drugs is the sustained elimination of all signs of the virus by week 12, allowing patients to stop treatment, though developers are aiming for the fastest cure rates possible. Vertex noted that 11 of 46 treatment naïve patients with the genotype 1a and 1b virus met the criteria of having "undetectable hepatitis C virus at weeks two and eight of treatment and were therefore eligible to stop all treatment at 12 weeks. Nine of these 11 patients achieved SVR4 (undetectable hepatitis C virus four weeks after the end of all treatment)." Data showed that viral loads were below the "lower limit of quantification" for 83% of the patients at week 12.
Vertex Announces 12-Week On-Treatment Data and SVR4 From Phase 2 Study of Interferon-Free (All-Oral) Treatment Regimen of INCIVEK®, VX-222 and Ribavirin in People with Genotype 1 Hepatitis C
- Company plans to start Phase 2b study in Q3 2012 to evaluate this interferon-free combination regimen in a total treatment duration as short as 12 weeks -
- Vertex also announces the advancement of its broad portfolio of direct acting antivirals, including its two structurally-distinct nucleotide polymerase inhibitors -
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (NASDAQ: VRTX) today announced interim data from two treatment arms of the Phase 2 ZENITH study evaluating an interferon-free (all-oral) treatment regimen of the non-nucleoside polymerase inhibitor VX-222 in combination with INCIVEK ® (telaprevir) tablets and ribavirin in people with genotype 1a or 1b hepatitis C who were new to treatment. Interim data showed that viral loads were below the lower limit of quantification ( < 25 IU/mL: < LLOQ) for 80 percent (37/46) of patients with genotype 1 hepatitis C at week two and 83 percent (38/46) of patients with genotype 1 at week 12.
ZENITH was designed with strict response-guided criteria that determined whether a patient was eligible to stop all treatment at 12 weeks. Eleven patients met the criteria of having undetectable hepatitis C virus at weeks two and eight of treatment and were therefore eligible to stop all treatment at 12 weeks. Nine of these 11 patients achieved SVR4 (undetectable hepatitis C virus four weeks after the end of all treatment). Data from ZENITH have been submitted for presentation at a medical meeting in the first half of 2012.
Click To Enlarge
† 19 patients completed 12 weeks of treatment: Two patients discontinued due to adverse events. One patient had virologic failure. One patient withdrew consent.
‡ 20 patients completed 12 weeks of treatment. Two patients had virologic failure. One patient was lost to follow up.
* HCV RNA < 10 IU/mL
** HCV RNA < 25 IU/mL
^ The two patients who did not achieve SVR4 relapsed during the post-treatment follow-up period.
The three drug regimen was generally well-tolerated. The majority of adverse events were reported as mild. There were no cases of moderate or severe rash and no discontinuations due to rash or anemia in the interferon-free study arms. There were two discontinuations due to adverse events in the genotype 1b arm of the study.
Vertex Advances INCIVEK, VX-222 and Ribavirin Combination Regimen
Based on these data, and pending discussions with regulatory agencies, the company intends to pursue a Phase 2b study evaluating multiple interferon-free combination regimens of INCIVEK, VX-222 and ribavirin with total treatment durations as short as 12 weeks in people with genotype 1 (1a and 1b) hepatitis C who are new to treatment. The new study will not use response-guided treatment criteria. If successful, data from this study will be used to design a Phase 3 program with the goal of submitting a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Vertex's first interferon-free regimen for genotype 1 (1a and 1b) patients by the end of 2014 or beginning of 2015, pending regulatory discussions.
"Since its approval INCIVEK has been used to treat tens of thousands people with hepatitis C and we're committed to further improving the care of those living with this disease by evaluating multiple interferon-free regimens," said Peter Mueller, Ph.D., Executive Vice President, Global Research and Development, and Chief Scientific Officer for Vertex. "Our ultimate goal is to develop well-tolerated, interferon-free treatment regimens with high viral cure rates and short treatment durations for people with hepatitis C. We believe we're well-positioned to achieve this goal by exploring various combinations within our portfolio that includes INCIVEK, VX-222 and two structurally-distinct nucleotide polymerase inhibitors."
Advancing Development of Two Nucleotide Polymerase Inhibitors
As part of a broad strategy to develop interferon-free regimens, Vertex and its collaborator Alios BioPharma are conducting Phase 1 studies of two structurally-distinct nucleotide polymerase inhibitors, known as ALS-2200 and ALS-2158. Vertex announced today that it has begun the first 7-day viral kinetic studies of ALS-2200 and ALS-2158 in people with genotype 1 hepatitis C. Safety and viral kinetic data from these studies are expected in the second quarter of 2012, which could enable the initiation of Phase 2 studies in the second half of 2012 to evaluate multiple interferon-free combination regimens of ALS-2200, ALS-2158, INCIVEK, VX-222 and/or ribavirin.
About ZENITH
ZENITH is an ongoing Phase 2 study that enrolled 152 people with genotypes 1a and 1b chronic hepatitis C who had not been previously treated to evaluate multiple response-guided treatment regimens with VX-222, Vertex's non-nucleoside polymerase inhibitor in development, in different combinations with INCIVEK, Pegasys® (pegylated-interferon alfa-2a) and Copegus® (ribavirin), three medicines approved to treat hepatitis C. In all arms, patients were eligible to stop all treatment at 12 weeks if they had undetectable hepatitis C virus at weeks 2 and 8. The primary endpoint of the study is safety and tolerability. The secondary endpoint is on-treatment antiviral activity and the proportion of people in each treatment arm who achieve a sustained viral response.
About INCIVEK and VX-222
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 25,000 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 Tibotec BVBA 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). Through its affiliate, Janssen, Tibotec 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®.
VX-222 is an oral medicine in development that is a non-nucleoside inhibitor of the HCV NS5B polymerase. Vertex has worldwide commercial rights for VX-222.
About ALS-2200 and ALS-2158
ALS-2200 and ALS-2158 are nucleotide analogues that appear to have a high barrier to drug resistance based on non-clinical and in vitro studies. Both compounds are designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. Each compound is structurally distinct (adenosine and uracil) and has its own unique mechanism of action, which supports the potential for developing these compounds together as a dual nucleotide regimen and as part of combination therapy regimens, including regimens with INCIVEK and VX-222. Data from in vitro studies showed that both ALS-2200 and ALS-2158 had a synergistic effect when combined together and with INCIVEK and VX-222. Additionally, in vitro studies ofboth compounds showed antiviral activity across all genotypes, or forms, of the hepatitis C virus, including genotypes more prevalent outside of the United States.
Vertex gained worldwide rights to ALS-2200 and ALS-2158 through an exclusive worldwide licensing agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also includes a research program that will focus on the discovery of additional nucleotide analogues that act on hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research program.
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.9 Hepatitis 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 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 About Forward Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including Dr. Mueller's statements in the sixth paragraph of this press release and statements regarding (i) Vertex's plan to start a Phase 2b study in Q3 2012 to evaluate this interferon-free combination regimen in a total treatment duration as short as 12 weeks; (ii) Vertex's plan to advance its broad portfolio of direct acting antivirals; (iii) the company's intent to pursue a Phase 2b study evaluating multiple interferon-free combination regimens and the potential design of this study; (iv) the company's plan to use data from the Phase 2b study to design a Phase 3 program with the goal of submitting an NDA for its first interferon-free regimen by the end of 2014 or beginning of 2015; and (v) the data that the company expects to receive from ongoing studies of ALS-2200 and ALS-2158 in the second quarter of 2012 and the possible initiation of Phase 2 studies involving ALS-2200 and/or ALS-2158 in the second half of 2012. 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 interim data presented in this press release may not be predictive of the final outcomes from this clinical trial; the outcomes from any future clinical trials of VX-222, ALS-2200 and/or ALS-2158 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. Vertex Contacts: Media:
Dawn Kalmar
Erin Emlock
Zach Barber
617-444-6992 mediainfo@vrtx.com
or Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
Source: Vertex Pharmaceuticals Incorporated
News Provided by Acquire Media
First-line hepatitis C therapy which includes a protease inhibitor can be cost-effective, investigators show in the Annals of Internal Medicine. The study showed that a triple combination of drugs, including the cheaper of the newly licensed protease inhibitors, was most cost-effective after screening for a gene mutation associated with response to hepatitis C treatment for patients with advanced fibrosis.
“Our study supports the important role of protease inhibitors in treating chronic HCV [hepatitis C virus] for patients with advanced fibrosis as part of a first-line regimen,” write the authors. Read more here...
NATAP Updates- Presented at the 22nd Conference of the Asian Pacific Association for the Study of the Liver (APASL)
Taipei, Taiwan
February 16-19, 2012
Dr. Jose Oliva, Allegheny General Hospital hepatologist and medical director of the liver transplant program, was interviewed on NBC Nightly News by Dr. Nancy Snyderman about the Hepatitis C epidemic and how it is affecting baby boomers. A patient at AGH's Center for Digestive Health was also interviewed about her experience.
From Medscape Medical News Birth Cohort Testing for HCV Saves Lives, Study Suggests
Yael Waknine
February 21, 2012 — Birth cohort testing and treatment for hepatitis C viral infection (HCV) in the primary care setting is cost-effective and could save thousands of lives each year, suggests a study from the US Centers for Disease Control and Prevention (CDC) published online November 4 and in the February 21 issue of Annals of Internal Medicine.
HCV infection is most prevalent among Americans born between 1945 and 1965, and 50% to 75% of those infected are unaware of their status. HCV caused between 7000 and 13,000 deaths in 2005. Experts project that this number will climb to 35,000 a year by 2030 if new case identification strategies are not implemented.
At this time, the CDC recommends HCV-antibody screening only for individuals with known risk factors such as a history of injecting drugs, requiring a blood transfusion before 1992, or receiving chronic hemodialysis.
Using a computer model, David Rein, PhD, principal research scientist, Public Health Research Department, National Opinion Research Center at the University of Chicago, Illinois, and colleagues estimate that screening of the population born between 1945 and 1965, followed by standard treatment for infected individuals with pegylated interferon and ribavirin (PEG-IFN + R), would reduce deaths by 82,300 compared with risk-based screening. The estimated cost of birth cohort screening and treatement is $15,700 per quality-adjusted life-year (QALY) gained.
Adding a direct-acting antiviral drug (DAA) to the treatment of patients identified with genotype 1 disease would prevent 121,000 deaths compared with risk-based screening, at a cost of $35,700 per QALY gained.
"The important things to remember about birth cohort screening are that, first, the strategy would identify over 800,000 people with hepatitis C if it were fully implemented, and second, the strategy is at least as cost-effective as many routinely administered preventive practices such as breast cancer screening or colorectal screening," Dr. Rein said in a news release.
Birth Cohort Screening Identifies More Than 800,000 New Cases
For the study, researchers developed a computer model to simulate the cost-effectiveness of 4 scenarios: no screening or treatment, risk-based screening and treatment with PEG-IFN + R, a 1-time birth cohort screening of people born from 1945 through 1965 with PEG-IFN + R, and birth cohort screening with PEG-IFN + R for patients with HCV genotypes 2 or 3 and PEG-IFN + R and DAA for those with genotype 1 disease, which is the most prevalent in the United States.
The researchers found that birth cohort screening during an annual primary care visit led to the identification of 808,580 more cases than risk-based screening, at a cost of $2874 per diagnosis.
With no screening, an estimated 618,000 birth cohort members would develop decompensated cirrhosis (DCC) or hepatocellular carcinoma (HCC) and die of hepatitis. Under risk-based screening, 14.8 million individuals were tested, 135,000 were treated, and 53,000 achieved sustained virologic response (SVR); 592,000 developed DCC or HCC and died of HCV-related disease.
In contrast, birth cohort screening with standard treatment led to the identification of 1,070,840 new cases among 60.4 million people tested; 552,000 patients were treated, and 229,000 achieved SVR, reducing the death toll to 509,000 (a drop of 82,000 compared with risk-based screening).
Birth cohort screening with DAA plus standard therapy also increased the number of identified cases but increased the number of patients achieving SVR by 311,000 and reduced the number of HCV-related deaths to 470,000 (a decrease of 121,000 deaths vs risk-based screening).
Compared with risk-based screening, birth cohort screening with PEG-IFN + R therapy increased QALYs by 348,000 and medical costs by $5.5 billion, for an incremental cost-effectiveness ratio (ICER) of $15,700 per QALY gained (95% credible interval [CI], $11,500 - $30,100).
Birth cohort screening and treatment with PEG-IFN + R plus DAA as needed led to a 532,000 increase in QALYs at a cost of $19.0 billion, for an ICER of $35,700 per QALY saved (95% CI, $28,200 - $47,200).
"This is a phenomenal incremental cost-effectiveness ratio and will only improve as sustained treatment efficacy increases with newer regimens," write Harvey J. Alter, MD, and T. Jake Liang, MD, from the National Institutes of Health in Bethesda, Maryland, in an accompanying editorial, noting that unlike HIV, HCV is not integrated in the host genome, and therefore is eradicable after only 6 to 12 months of antiviral therapy.
Study limitations include the lack of real-world data on the efficacy of newer HCV drugs; exclusion of uninsured, institutionalized, and homeless patients; and the capping of disease duration at 20 years, making the screening intervention seem slightly less cost-effective.
Identification of Asymptomatic HCV Is Key
"As innovative treatments for hepatitis C follow their now-destined progression, the most burning question will not be whether to treat, but rather how to identify the many chronic HCV carriers who are unaware of their infection and are at risk for cirrhosis, end-stage liver disease, or hepatocellular carcinoma," note Dr. Alter and Dr. Liang.
Effective national implementation of programs for prevention and care similar to that employed to combat the AIDS epidemic is key to achieving a reduction in HCV mortality over time, they note, adding that HCV deaths now outstrip those associated with HIV.
Expansion of HCV screening practices to include routine testing of individuals born between 1945 and 1965 represents a cost-effective strategy and should be implemented as a national health policy, Dr. Alter and Dr. Liang conclude.
The study was supported by grants from the US Centers for Disease Control and Prevention's Division of Viral Hepatitis. The authors and editorialists have disclosed no relevant financial relationships.
Ann Intern Med. 2012;156:263-270, 317-319
Journalist
Yael Waknine
Yael Waknine is a freelance writer for Medscape.
Mortality and the risk of malignancy in autoimmune liver diseases
February's issue of Hepatology investigates mortality and the risk of malignancy in autoimmune liver diseases.
Population-based quantitative data on the mortality and cancer incidence of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis are scarce.
Dr Catherine Stedman and colleagues from New Zealand systematically investigated the survival and risk of malignancy on population-based cohorts of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis.
Multiple case-finding methods were employed, including searches of all public and private, adult and pediatric outpatient clinics, hospital notes, laboratory, radiology, and pathology reports.
Cases that fulfilled standardized diagnostic criteria were included.
A receiver operating characteristic curve analysis showed sensitivity of 91%
Hepatology
Kaplan-Meier survival estimates, standardized mortality ratios, and standard incidence ratios for malignancy were calculated.
A total of 130 autoimmune hepatitis, 70 primary biliary cirrhosis, and 81 primary sclerosing cholangitis patients were included contributing to 1,156, 625, and 613 person-years at risk, respectively.
For autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis cohorts, standardized mortality ratios for all-cause mortality were 2.1, and 4.1.
The team found that the standardized mortality ratios for hepatobiliary mortality were 42, 71, and 117 for autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis cohorts.
The research team noted that the standard incidence ratios for all cancers were 3, 1.6, and 5.2 for autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis cohorts.
The standard incidence ratios for extrahepatic malignancy were 2.7, 1.6, and 3.0, for autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis cohorts, respectively.
Dr Stedman and colleagues comment, "This is the first population-based study to examine and compare the survival and cancer incidence in autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis in the same population."
"The mortality for all 3 cohorts was significantly increased due to liver-related death, demonstrating the inadequacy of current management strategies."
"The risk of hepatic and extrahepatic malignancy was significantly increased in autoimmune hepatitis and primary sclerosing cholangitis patients."
Exercise test to predict survival after liver transplantation
Submaximal cardiopulmonary exercise testing predicts 90-day survival after liver transplantation, reports this month's Liver Transplantation.
Liver transplantation has a significant early postoperative mortality rate.
An accurate preoperative assessment is essential for minimizing mortality and optimizing limited donor organ resources.
Dr James Prentis and colleagues from the United Kingdom assessed the feasibility of preoperative submaximal cardiopulmonary exercise testing for determining the cardiopulmonary reserve in patients being assessed for liver transplantation.
In addition, the team investigated its potential for predicting 90-day posttransplant survival.
The team found that 182 patients underwent cardiopulmonary exercise testing as part of their preoperative assessment for elective liver transplantation.
The 90-day mortality rate, critical care length of stay, and hospital length of stay were determined during the prospective posttransplant follow-up.
The research team noted that 91% of patients successfully completed cardiopulmonary exercise testing.
The researchers defined this as the ability to determine a submaximal exercise parameter, termed the anerobic threshold.
A receiver operating characteristic curve analysis showed sensitivity of 91%
Liver Transplantation
The team observed that 33% underwent liver transplantation, and the mortality rate was 10%.
The mean anerobic threshold value was significantly higher for survivors versus nonsurvivors.
Logistic regression revealed that anerobic threshold, donor age, blood transfusions, and fresh frozen plasma transfusions were significant univariate predictors of outcomes.
The researchers found that only anerobic threshold was retained as a significant predictor of mortality.
A receiver operating characteristic curve analysis demonstrated sensitivity and specificity of 91% and 83%, respectively, with good model accuracy.
The optimal anerobic threshold level for survival was defined to be more than 9.0 mL/minute/kg.
The research team found that the predictive value was improved when the ideal weight was substituted for the actual body weight of a patient with refractory ascites, even after a correction for the donor's age.
Dr Prentis' team concludes, "In conclusion, the preoperative cardiorespiratory reserve is a sensitive and specific predictor of early survival after liver transplantation."
"The predictive value of cardiopulmonary exercise testing requires further evaluation."
Risk factors for hepatitis C virus acquisition by ethnicity
A study in February's issue of the Journal of Viral Hepatitis identifies risk factors for hepatitis C virus acquisition by Caucasian, Hispanic, and Asian American patients.
Commonly known risk factors for infection with hepatitis C virus (HCV) include blood transfusion, injection drug use, intranasal cocaine use, and body tattoos.
Dr Nguyen and colleagues from California, USA hypothesized that Asian Americans infected with HCV may not identify with these established risk factors present in Caucasians and Hispanics.
The team surveyed risk factors in HCV-infected patients in these ethnic groups in a prospective study.
The most common risk factors in Asians were blood transfusions, and acupuncture
Journal of Viral Hepatitis
The team reported that 494 patients infected with HCV completed a detailed risk assessment questionnaire at a liver centre in Northern California from 2001 to 2008.
Among subjects participating in this study, 55% identified themselves as Caucasian, 20% as Hispanic, and 25% as Asian. Asian Americans were older, less likely to smoke or consume alcohol, and have a family history of cancer compared with Caucasians and Hispanics.
The laboratory profiles were similar, and genotype 1 was the most common infection in all groups.
The great majority of Caucasians and Hispanics identified with commonly known risk factors, which was in contrast to 67% of Asians.
The team found that the most common risk factors in Asians were blood transfusions, and acupuncture.
In addition, the team observed that 74% of Caucasians and 66% of Hispanics identified more than 1 major risk factor, while only 20% of Asians reported having more than 1 risk factor.
Dr Nguyen's team concluded, "Survey for established risk factors for acquisition of HCV may be more appropriate for risk assessment of Caucasians and Hispanics, but not for Asian Americans."
"These findings may guide the development of HCV screening in our increasingly diverse population."
Discussion Only Full Text
Hepatitis C is a major health risk and economic burden, which could be alleviated by the delivery of therapy and cure to those infected. In Tayside there were just under 1000 individuals diagnosed with HCV, at the end of the study period: of those, over 70% have attended at least one appointment at the specialist treatment services and of those 40% have been successfully commenced on treatment. This is considerably higher than the pyramid of care reported by National Institute of Clinical Excellence and other surveys.[11] Clearly, this proportionately large unselected treatment cohort will accurately reflect real world issues and include those with ongoing issues around drug misuse. Indeed given the relative ease with which this part of the population at risk of HCV infection can be identified they are frequently over represented in unselected cohorts. If treatment for HCV infection is to make a difference to the natural history of the HCV epidemic at a population level then those infected with HCV must be brought into therapy with no bias against the IDU population. Therapy for HCV is regarded as cost-effective,[12–14] but this evaluation is critically dependent on the success of the therapy, the SVR, and this is highly dependent on adherence to therapy. This concern over lack of adherence reducing the efficacy of therapy has been the traditional reason for exclusion of those patients with an IDU background from therapy. This study seeks to answer this question: is the concern over the treatment of IDU patients with chronic hepatitis C justified on the basis of SVR?
We have assessed the treatment outcome in 291 consecutively treated, predominately treatment-naive patients who received pegylated interferon and ribavarin for HCV. In contrast to much of the UK, due to record linkage, we know this represents 31.4% of the total diagnosed population in our community. They represent a typical unbiased clinic cohort. Of the three groups the non-IDU cohort was older and slightly overweight. As expected they had a higher number of cirrhotic individuals, though this does achieve significance when compared to the IDU group (Ex and active).
The sustained virological response was the highest in the non-IDU group with 61.5%, followed by 54.8% in the ex-IDU patients, with active IDU patients achieving an SVR of 47.1% of patients. This represents the worse case scenario as those patients with missing SVR data were regarded as treatment failures. This outcome was particularly common in the active IDU group, which contained a much higher number of prisoners, who upon liberation were lost to our care, as they did not reside in Tayside. These patients had fully completed therapy and could be expected to have high SVR rates. We therefore performed an analysis excluding these missing values. Unsurprisingly this improved the SVR rates for all groups and narrowed differences between the groups, which continued to show no significant differences other than ex and active IDU with nongenotype 1 infection. The overall SVR rates are slightly lower than the landmark randomized control trials (RCTs) however none of the trials treated active drug users and ex-IDU were only included if stable for >12 months.[5,6] Secondly our non-G1 patients are almost exclusively genotype 3, which will have a worse outcome compared to that of the non-genotype 1 RCT groups which have a large genotype 2 cohort. It has been shown in various cost effectiveness analysis that combination therapy prolongs life, improves quality of life and is cost-effective.[15] But these analyses were based on the results of the RCTs as models and hence excluded patients with intravenous drug use. These studies are based on patients with chronic HCV achieving overall SVRs of 55% (95% CI 52–58%) and for genotype 1 SVRs of 36–46% and for nongenotype 1 of 61–76%.[4–6] The results of our investigation fall within this range with the exception of the ex-IDU genotype 1 subgroup, which had an excess of cirrhotic patients, however the reported values in this study are still within the range to make the therapy cost effective. Clearly genotype is the most significant predictor of SVR. When this is taken into account the reassuring theme that comes across is whether it is genotype 1 with the longer treatment course where the SVR rate in the active drug user was 42.3%, or the relatively shorter treatment of non-G1, where the active IDU had treatment success in 56.6%, these results lie in the SVR range that has been demonstrated to be cost-effective. The regression analysis performed found the usual predictors of SVR such as genotype and age, but did not find significant reductions in chance of SVR in those from IDU backgrounds, while the confidence intervals in the analysis are wide due to sample size, the sample did identify genotype and age as factors reducing the chance of SVR and we still offer therapy to older genotype 1 patients. Overall the results do not differ significantly in the non-IDU group, thus confirming the message: active IDU is not a barrier to treatment or a successful achievement of SVR.
Another key question is: What is the additional patient support needed to achieve the SVRs reported in this paper? A local redesign of HCV treatment services introduced a new referral pathway in 2004, implementing strategies to improve attendance and outreach clinics within the Tayside Drug Problems Service. This model utilizes existing staff working smarter in an extended role, minimising additional staffing costs. This led to an increase in referral rates. These changes in services generated a large number of patients in the early stages of drug addiction treatment coming forward for assessment of HCV. This provided us the opportunity to assess efficacy of therapy in such a group of patients.[10] In essence, the pathway is dependent upon nurse specialists delivering the anti-viral therapy; this would now be regarded as the standard of care for HCV therapy. The care pathway is patient focussed, so for patients in active treatment for addiction the HCV therapy is co-delivered with their addiction therapy, thus minimizing the need for the patient to travel to other clinics and intimately involving the drug key worker as well as the nurse specialist in the patient's treatment. This involves the nurse specialist in outreach work but requires little additional expenditure on staff other than minimal transport costs, particularly as several patients can be seen in one session.
Our results do show that with simple support provided by a dedicated team of nurses, drug addiction workers, social services and physicians working in partnership can result in SVR rates in the active drug user group comparable with non-IDU infected individuals. This maintains the cost effectiveness of antiviral therapy for HCV in these patient groups. The intervention is designed around existing staff working smarter, rather than expensive alternatives hence a generalizable solution for the National Health Service and possibly throughout the world. Finally, it offers the patient the prospect of a better chance of cure and a positive healthcare experience.
