Treating HCV- Learning The Basics

HCV- Learning The Basics

Happy Tuesday folks, hope you all had a great weekend. Since a new week is just beginning why not try something new by using an online learning activity to gain additional knowledge about HCV?

The HCV landscape is quickly changing, with many new investigational agents making their way to FDA approval, and newer treatments now available that require shorter treatment duration, less side effects and higher cure rates. 

In order to gain a better understand of treating HCV, a review of the basics, especially treatment response, is a necessary first step. By doing so, participating in the decision process and communicating with a healthcare provider is made easier, if treatment is needed.

A good  place to start is with this video presentation by The American Association for the Study of Liver Diseases (AASLD) which include eight modules discussing the following topics;

Modules 

Hepatitis C

• Module 1: HCV: Epidemiology and Screening
• Module 2: Patient with New Diagnosis of HCV (anti-HCV positive)
• Module 3. Assessing Severity of Liver Disease in HCV
• Module 4: Management of the Patient with Chronic HCV
• Module 5. Management of the Chronic HCV Patient with Co-Morbid and Other Conditions
• Module 6. Antiviral Treatment of the Patient with HCV Infection
• Module 7. Management of Patients with HCV who have achieved a Virological "Cure"
• Module 8. The Pediatric Patient with HCV

** The CME offers information on hepatitis B as well. 

Hepatitis B

• Module 1: HBV: Epidemiology and Screening
• Module 2: Patient with Positive Hepatitis B Serologies
• Module 3. Natural History of HBV and Identification of Treatment Candidates
• Module 4. Management of the Chronic HBV Patient with Co-Morbid and Other Conditions
• Module 5: Antiviral treatment of the Patient with Chronic HBV
• Module 6: Prevention of HBV Infection
• Module 7: Hepatitis B in the Pediatric Patient

Although the learning activity is for healthcare professionals, the savvy patient will benefit greatly from reviewing the program.

First time participants should register here, before clicking on the links provided below. After this is achieved, come back and follow the instructions for navigating the activity. The goal is to learn more about managing and treating HCV, since we are not healthcare professionals earning a CME credit, or taking the pretest isn't necessary. Skip these steps by using the following tips.

Navigating The Program

Register here, type in all required fields marked with the red asterisk *

Next, click here. 

After landing on the CME, click on; First step: Self needs-assessment questions

The user will be prompted to answer two questions, and asked to choose from a drop down menu under "Which Topics" answer as seen below. 

Click Submit

Click on the first module to view the video presentation; Module 1: HCV: Epidemiology and Screening

Click on "Presentation" ignore the pre-test, post-test or the evaluation form. 

After clicking on "Presentation" a pop up will appear asking you; Do you wish to receive credits for this activity? 

Respond with no. 

Another pop up will appear warning no credit will be issued for taking the CME.
Respond with, okay. 

The program will begin.

If you decide to only review one module, check out; Antiviral Treatment of the Patient with HCV Infection narrated by Dr. Michael Fried discussing current and new therapies for HCV. This module is newer, released on April 10, 2014. 

In addition, this month a new section was added to AASLD/IDSA recommendations for testing, managing, and treating Hepatitis C titled; When and in Whom to Initiate HCV Therapy. Recently, Alan Franciscus, Editor-in-Chief at HCV Advocate offered a review with commentary on the update, view the entire report here, on their website.

Finally, a self-study, interactive; Hepatitis C Online Course, covering other conditions related to the virus, disease progression, noninvasive tests for diagnosing liver fibrosis, treatment and so much more, is most certainly a valuable tool worth exploring. The course is provided by the University of Washington and includes a collaboration with the International Antiviral Society-USA (IAS-USA). Funded by a grant from the Centers for Disease Control and Prevention.

Enjoy, see you soon.
Tina

UK Says Sovaldi Is Worth It. We Should Listen.

UK Says Sovaldi Is Worth It. We Should Listen.

Yevgeniy Feyman

It’s rare that I get to say this – but we can learn something from the United Kingdom. As our “free-market” health care system deliberates whether Gilead is charging a “just” price for its Hepatitis C (HCV) drug, Sovaldi, the UK’s National Institute for Health and Care Excellence (NICE) just approved the drug as being cost-effective, and recommended it for subgroups of patients...

The battle over Sovaldi – which costs $84,000 in the U.S. for a full course of treatment – has sparked not only outrage from insurers and pharmacy benefit managers (PBMs), but also a Senate investigation into pricing of the drug.....

Continue reading here...

Of Interest
Reducing the cost of new hepatitis C drugs 
A collection of current articles addressing the high price of Gileads HCV drug Sovaldi.

How Do NS5A Inhibitors Prevent HCV Replication?

How Do NS5A Inhibitors Prevent HCV Replication?
Kristine Novak

Researchers have uncovered the mechanisms of drugs that inhibit the hepatitis C virus (HCV) non-structural protein 5A (NS5A), described in the August issue of Gastroenterology. In a quantitative analysis of the kinetics of NS5A inhibitors, David R. McGivern et al. show that these agents rapidly inhibit intracellular assembly of virions and inhibit formation of functional replicase complexes, but have no activity against preformed replicase.

NS5A inhibitors are likely to become an important component of hepatitis C treatment regimens, yet their exact mechanism of action are unclear. NS5A has no known enzymatic activity and no cellular orthologs or viral homologs, other than NS5A proteins of other hepaciviruses. However, NS5A functions in multiple aspects of the HCV life cycle.

McGivern et al. performed detailed kinetic analyses of specific steps in the HCV life cycle using cell cultures incubated with protease inhibitors, polymerase inhibitors, or NS5A inhibitors.

The authors found that the NS5A inhibitors blocked HCV RNA synthesis more slowly than protease or polymerase inhibitors. By 24 hours after addition of an NS5A inhibitor, polyprotein synthesis was reduced <50%, even at micromolar concentrations.

In contrast, inhibition of virus release by NS5A inhibitors was potent and rapid, occurring within 2 hours. Cells incubated with NS5A inhibitors were rapidly depleted of intracellular infectious virus and RNA-containing hepatitis C virus particles, indicating a block in virus assembly.

McGivern et al. provided direct evidence for an immediate (<3 hours) effect of NS5A inhibitors on the intracellular assembly of HCV. In the absence of inhibitors, NS5A is distributed between membrane-bound viral replicase complexes derived from the endoplasmic reticulum, where NS5A functions in RNA replication, and lipid droplets, to which it is recruited by core protein and functions in viral assembly. NS5A inhibitors induce a redistribution of NS5A within the cell, into large, cytoplasmic aggregates. The authors propose that the inhibitors bind NS5A in proximity to the lipid droplet, given their effect on virus assembly.

In addition to their immediate effect on virus assembly, NS5A inhibitors potently induced an early (<12 hours), but only partial block in viral RNA synthesis.

In an editorial that accompanies the article, Menashe Elazar and Jeffrey S. Glenn explain that although NS5A has independent roles in RNA replication and particle production, these functions might be tightly linked. Inhibition of RNA replication by other drugs could lead to a NS5A-mediated immediate shut down of particle assembly (see figure). This type of linkage could provide a mechanism for HCV to prevent further packaging of viral genomes and instead divert them to serve as templates, allowing them overcome the inhibition of RNA replication.

Although NS5A inhibitors have not been approved for treatment of hepatitis C, there are several in clinical phases of development. These include daclatasvir, ledipasvir, and MK-8742. McGivern et al. state that these inhibitors show substantial therapeutic promise, with 50% effective concentrations in replicon assays in the low picomolar range, making them the most potent class of anti-HCV agent.

The authors conclude that their findings complement recent efforts to develop multiscale mathematical models of the clinical response to antiviral agents. They state that further research is needed to elucidate the full viral life cycle, which would increase our understanding of antiviral activity and resistance.

Source

Updated - Debunking the Myths of Treating Hepatitis C

Debunking the Myths of Treating Hepatitis C 
 08.05.14 | By Jennifer Wall

Original publish date was 7/21/2014; this post was updated on 8/5/2014.
A national dialogue is needed around the value of new medicines and cures and the role they play in improving patient health and helping to manage long-term spending in the U.S. health care system.   Unfortunately, the debate around hepatitis C has, for the most part, been twisted to the point that modern-day cures are seen as a nuisance rather than a monumental step forward in the battle against disease.  For this reason, it is important to set the record straight on some of the misperceptions about the value of new and forthcoming hepatitis C treatments.

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Myth: New treatments for hepatitis C could double prescription drug spending in 2014.
Fact: New treatments for hepatitis C are projected to increase health care costs by ONLY half a percent in 2014.

• New cures for hepatitis C can help prevent up to $85 billion in medical costs in the U.S. health care system. 
• A recent report by PricewaterhouseCoopers found that these new treatments would actually have a minor effect on growth in 2014.  In fact, the report projects that new hepatitis C treatment will impact growth in health care costs in 2014 by only a half a percent but the impact will fall in future years and level off after 2016 as patients are cured. 
  • The report also notes that “long-term savings for chronic treatments, liver transplants, and lost productivity may ultimately offset the cost of these specialty drugs for the most seriously ill patients.”
• IMS Health estimates that total drug spending, including specialty medicines, is projected to remain at historically low levels, averaging one to four percent annually until 2017.
• Hepatitis C is the leading cause of cirrhosis, liver cancer and liver transplantation, and the medical costs associated with these very serious complications are no minor expense.
  • End stage liver disease average annual treatment costs are estimated at $59,995 per patient and for those with liver cancer, costs are estimated at $112,537.
  • Liver transplant costs range as high as $500,000 and require many years of costly follow up care.

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Myth: New treatments for hepatitis C are not worth the cost.
Fact: New and forthcoming hepatitis C treatments can cure over 90 percent of patients, providing tremendous value to patients and society.

• Until recently, available therapies used to treat HCV infection cured only about half of patients, but with debilitating flu‐like side effects. For those who failed to respond to treatment, there were no alternative medicines to treat the disease.
• With new and forthcoming treatments, patients will be more likely to adhere to their medication regimens given that there are fewer side effects and non-injectable options are now available.
• The availability of more effective treatments provide the opportunity to improve outcomes for HCV patients who are frequently unable to work or have significantly more lost work days per employee than other workers, including sick leave, short‐term disability, and long‐term disability.

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Myth: All three million people estimated to have hepatitis C in the U.S. will be treated with new medicines in 2014.
Fact: More than three out of four people with hepatitis C do not know they are infected and are therefore unlikely to seek treatment for the disease this year.

• Unfortunately, progression of the disease occurs slowly, meaning patients often remain asymptomatic, and unaware they are infected, until very serious and often expensive complications emerge.
• Even among those Americans seeking testing, half do not return to obtain their results and are therefore unaware of their infection.
• Among those in the commercially insured market, PricewaterhouseCoopers estimates that only about 60,000 hepatitis C patients will be treated in 2014.

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Myth: Payers will pay the list price of new hepatitis C treatments for all patients getting treated.
Fact: Insurers negotiate prices with drug manufacturers and the government mandates discounts in some public programs.

• The Medicaid and the Veterans Affairs program receive statutorily-set rebates on prescription medicines, plus additional rebates in some instances.
• Plans and biopharmaceutical manufacturers also negotiate discounts and rebates on medicines in both the Medicare Part D program and commercial markets.
• Potential savings could be realized from competition as more hepatitis C medicines enter the market over the next year.

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Myth: New treatments for hepatitis C will blow up Medicare Part D costs and drive up beneficiary premiums.
Fact: The Centers for Medicare and Medicaid Services announced that estimated average premiums for 2015 will be $32/month, an increase of only $1 from 2014.

• Beneficiary premiums remain about half of the $60 originally forecast for 2015.
• Part D premiums are determined through a competitive bidding process. Each year, insurance companies submit bids to the government for the cost of providing prescription drug coverage; beneficiaries then pay a portion of those costs through premiums. The national average monthly bid amount is projected to decline for the 5^th year in a row to about $70, a $5 decrease from 2014. Part D plan bids are actually lower today than they were in the first year of the program; the 2006 bid amount was about $92.
• The competitive nature of Part D gives plans and pharmacy benefit managers the tools they need to keep costs for beneficiaries low: “By offering an abundance of competing choices in each region and using cutting edge, cost-saving tools like pharmacy networks and home delivery the program is a win-win for both seniors and taxpayers," says PCMA President and CEO Mark Merritt.
• The Congressional Budget Office 10-year forecast for Part D spending continues to be reduced; for 2014 alone, it was reduced by $56 billion.

- See more

HCV Weekend Reading- Liver Health, Coffee and Genotype 3

Welcome to this edition of weekend reading, today the topic is hepatitis C and liver health. No surprise here.

On this warm August day, information is just a click away. Maybe an article on fatty liver, nutrition, or the benefit of drinking coffee may tickle your fancy. Who says that? Tickle your fancy?

In any event, catch up on what you missed, or come back at your leisure to further investigate any article of interest.

Lucinda K. Porter, RN

After I was diagnosed with HCV, I found myself online researching hepatitis C, ways to improve my overall health and treatment options. My search often lead me to Lucinda K. Porter, RN., a well known author and HCV advocate. Lucinda has written two books, countless articles for HCV Advocate, and graces our community with weekly articles, found here, on her incredible blog.

Lucinda is to the HCV community - what a Coast Guard-approved life jacket - is to a non-swimmer. By arming our community with lifesaving knowledge, she has saved us from drowning in a deep pool of misguided information.

I admire Lucinda, not only for her beauty; I think she resembles Gwyneth Paltrow, and apparently her granddaughter has inherited her good looks, but for her devotion to the families, and people living with this serious life altering disease.

HCV Genotype 3 - Cirrhosis and Cancer

Let us begin with an article written by our lovely Lucinda, found in the August issue of HCV Advocate's newsletter. Lucinda writes about the increased risk of cirrhosis and cancer in persons with hepatitis C, and genotype 3, reported recently in the journal Hepatology. Other topics in the article include information on noninvasive tests for liver fibrosis. Please click here to review the article, a good read - to be sure.

Fatty Liver and Hepatitis C

In other research, HCV genotype 3 has been associated with a higher risk of fatty liver disease, all genotypes can trigger the condition, but people with genotype 3 have a higher risk at 60% - 80% for developing moderate or severe steatosis. Steatosis is extremely common in people with chronic hepatitis C, close to 40% of people with hepatitis C have steatosis, compared to about 14% to 31% of the general population.  For more information check out this full text article published in BioMed Research International, April 2013 issue, found here.

Diet and Hepatitis C

We know there isn't really a diet for people living with HCV, (outside cirrhosis) however, a 2013 study published in Nutrition found that HCV patients who participated in a diet and exercise program lowered their grade of steatosis and, remarkably, their fibrosis score.

The Mediterranean Diet and Liver Health

When I was much younger, dieting was easy, as I grew older that wasn't the case. Today, I follow the Mediterranean way of eating. Check this out, researchers from St. Vincent's Hospital, in Melbourne, compared the Mediterranean Diet to the National Heart Foundation Diet and found people who followed the Mediterranean Diet reduced liver fat, inflammation and significantly improved insulin sensitivity. Food for thought for people living with hepatitis C, pun was accidentally intended.

"Weight loss is difficult to achieve and maintain; however this has previously been the only accepted therapeutic strategy for NAFLD," said Dr. Ryan, "We have now demonstrated that adherence to the Mediterranean Diet can reduce liver fat, and improve insulin sensitivity, without weight loss, thus reducing the risk of development of liver disease and Type 2 Diabetes Mellitus."

The study was presented at AASLD 2011.

Mediterranean Diet, Hepatocellular Carcinoma and Viral Hepatitis
This is exciting, could the diet help against liver cancer? What about people with viral hepatitis? According to a study found in the Journal of Hepatology, November 2013, it may;

A closer adherence to the Mediterranean diet appears to be protective against HCC (liver cancer). Our results also point to potential benefits from adhering to a Mediterranean dietary pattern for patients chronically infected with hepatitis viruses.

Read the full article over at NATAP, abstract here.

Coffee - Drink Up
Following a healthy diet can be difficult, but for most people drinking coffee has become part of our daily ritual. Fortunately, that morning cup of stimulation may have beneficial effects on liver disease, hepatitis C, fatty liver, even improved SVR rates after peg-interferon combination therapy.

Side Note
Although, interferon is most certainly not our drug of choice. Like you, I am elated that some people have and will benefit from treating with Sovaldi - without interferon. Soon additional new interferon sparing agents to treat HCV will be available at a pharmacy near you.

Coffee and Liver Cirrhosis
Back to coffee, findings in the November 2009 issue of Hepatology suggest consuming two or more cups of coffee each day reduces the risk of death from liver cirrhosis by 66%, specifically cirrhosis caused by non-viral hepatitis.

In summary, in a prospective study of individuals with hepatitis C and bridging fibrosis or cirrhosis at baseline, we found a significant inverse association between regular coffee intake and liver disease progression.

Continue reading...

In case you missed it, this commentary, published in the April 2013 issue of Gastroenterology looks promising;

Excerpt; Is It Time to Write a Prescription for Coffee? Coffee and Liver Disease

Based on the available data from predominantly observational trials, there seems to be a clinical benefit of coffee consumption for those patients at risk of developing hepatic fibrosis either from NAFLD or viral hepatitis. Rates of liver cancer and the development of metabolic syndrome may also be improved with daily moderate filtered coffee intake. CGA and caffeine are the best candidates for beneficial effects on hepatic fibrosis, and cafestol and kahweol may reduce rates of HCC. It is unclear whether any of these benefits are significant enough to “treat” patients with chronic liver disease and further study is required with standard doses of each of these purported therapies in appropriately powered, multicenter, randomized, controlled trials with both biochemical and hepatic histology as endpoints. In the interim, moderate daily unsweetened coffee ingestion is a reasonable adjunct to therapy for NAFLD patients that often includes lifestyle modification with diet and exercise.

So What About Those Liver Enzymes and Coffee

Alanine Aminotransferase (ALT) and Aspartate aminotransferase (AST)

Keeping with 2013, Published online in PLOS ONE, a peer-reviewed, open-access, online publication, a study concluded; Patients with Hepatitis C-related liver disease, who have a higher consumption of coffee, have a lower rate of disease progression than those drinking less coffee. 

Here is an excerpt from the article; Effect of Caffeine-Containing Beverage Consumption on Serum Alanine Aminotransferase Levels in Patients with Chronic Hepatitis C Virus Infection: A Hospital-Based Cohort Study

Coffee is one of the most commonly consumed beverages in the world. Its health benefits including improved overall survival have been demonstrated in a variety of disease states. To examine the association of coffee consumption with liver disease, a systematic review of studies on the effects of coffee on liver associated laboratory tests, viral hepatitis, nonalcoholic fatty liver disease (NAFLD), cirrhosis and hepatocellular carcinoma (HCC) was performed. Coffee consumption was associated with improved serum gamma glutamyltransferase, aspartate aminotransferase (ALT) and alanine aminotransferase (AST) values in a dose dependent manner in individuals at risk for liver disease. In chronic liver disease patients who consume coffee, a decreased risk of progression to cirrhosis, a lowered mortality rate in cirrhosis patients, and a lowered rate of HCC development were observed. In chronic hepatitis C patients, coffee was associated with improved virologic responses to antiviral therapy. Moreover, coffee consumption was inversely related to the severity of steatohepatitis in patients with non-alcoholic fatty liver disease. Therefore, in patients with chronic liver disease, daily coffee consumption should be encouraged.

Full article....

From Medscape Gastroenterology published April 14, 2014

Can Coffee Treat Liver Disease?

Daily consumption of coffee appears to have an effect on developing fibrosis in some liver diseases, especially alcoholic liver disease and NAFLD. In addition to improving liver tests, such as GGT and ALT, coffee appears to inhibit the development of fibrosis in chronic hepatic inflammatory disorders. Whereas reduction of fibrosis and a potential effect on the outcome of patients with chronic HCV infection has been demonstrated, a similar benefit for the HBV-infected patient is not as clear. Additional studies of the effect of coffee on cirrhosis of HBV infection are needed.

Furthermore, coffee appears to reduce the risk for HCC in patients who are at risk for the disease. Once again, the evidence for any effect of coffee on HBV-related liver cancer needs additional study.

Whether the effect of coffee on liver disease is related to caffeine or some other agent in coffee is not clear. However, many studies have failed to show a significant effect of other caffeine-containing drinks, such as green or black tea, on reducing fibrosis or inhibiting the development of HCC. 

Although we have treatments for many forms of chronic liver disease, alcoholics who continue to consume ethanol-containing beverages and patients with NAFLD who are unable to control their associated causal factors might benefit from drinking 2 or more cups of regular coffee daily. Whether this should be a boiled or filtered coffee preparation is probably up to the wishes of the patient. However, this recommendation for coffee is obviously an unapproved indication, and reaching a stronger conclusion will require many more studies. A careful conversation with patients at risk is needed before giving this advice.

Continue to Medscape to read full article...

Once again, several studies has shown coffee has may help to prevent liver inflammation, which is often related to hepatitis C, cirrhosis, and liver cancer. In this August 2013 systematic review , published online in the April 2014 issue of Liver International, (download PDF here, HTML here) researchers investigated several studies assessing the effect of coffee on liver disease.

Excerpt from Healio; Studies indicate protective effects of coffee for liver disease.

Review of six studies assessing coffee’s impact on cirrhosis indicated a reduced risk for progression among patients with chronic liver disease. Cirrhotic patients who consumed coffee also were found to be at lower risk for death in two case-control studies, with a greater benefit among patients who reported drinking three or more cups daily.

Several studies of patients with chronic hepatitis C indicated improved outcomes among coffee drinkers, with associations observed between coffee and reduced fibrosis severity and disease progression, plus improved response to antiviral therapy.  

“While the aforementioned studies … suggest that coffee is useful as an alternative medicine in the treatment of the most common types of liver disease, blinded, randomized controlled trials must be performed,” the researchers wrote, adding that the primary use of observational and cross-sectional studies, the lack of demographic information, standardization of coffee cup size and data on consumption at multiple time points were study limitations.

The complete easy to read study summary can be found online, here. 

This brings us to our final 2014 study; Intake of Coffee and Caffeine are Associated with Decreased Risk of Hepatitis C-related Hepatic Fibrosis presented at Digestive Disease Week in Chicago, provided by NATAP, which reported that drinking coffee may offer a protective effect against advanced hepatic fibrosis in persons with hepatitis C.

In closing, we end up where we began, with Lucinda and HCV Advocate. Provided below are some articles of interest for anyone newly diagnosed, considering therapy, undergoing therapy or living with HCV, brought to you by Lucinda and Alan Franciscus, and the great staff at HCV Advocate.

Newly Diagnosed
New Medications and Who Will Pay For Them, by Jacques Chambers, CLU
Use of FibroScan® in clinical practice, by Maurizio Bonacini, MD

HCV Drug Pipeline

The Latest Hepatitis C Treatment Recommendations: Who Decides Your Future? by Lucinda K. Porter

HCV Treatment Side Effects: Photosensitivity, by Alan Franciscus

Current drugs to treat hepatitis C

You can find Lucinda on Facebook and Twitter, search for clinical trials, or read the latest news on HCV Advocate's website or blog. Connect with HCV Advocate on Facebook and Twitter.  In addition, NATAP can be found on Twitter as well, for current research on new drugs to treat HCV visit their website.

Enjoy this wonderful weekend! Until next time.

Always Tina

Achillion's hepatitis C drug shows promise in trial

Achillion's hepatitis C drug shows promise in trial

(Reuters) - Achillion Pharmaceuticals Inc said all patients treated with its experimental hepatitis C drug showed no detectable levels of the virus four weeks after the therapy, sending its shares up 18 percent.

The mid-stage trial tested Achillion's drug, ACH-3102, in 12 patients in combination with Gilead Sciences Inc's Sovaldi, also known as sofosbuvir.

Achievement of 100 percent cure rate confirms the competitive profile of NS5A, Wells Fargo Securities analyst Brian Abrahams wrote in a note.

ACH-3102 belongs to a promising new class of drugs that work by blocking the NS5A protein needed by the virus to replicate.

Achillion is also working on a different class of drugs known as nucleotide inhibitor, or "nuc", and which has been the focus of investors' attention.

"This class of drug (ACH-3102) is not as unique an asset as ACH-3422, that's the nuc. If they have positive data, then they are going to have a very high likelihood of takeout just like Idenix," FBR Capital Markets & Co analyst Andrew Berens told Reuters.

Merck & Co Inc agreed in June to buy Idenix Pharmaceuticals Inc for $3.85 billion to boost its hepatitis c drugs portfolio. Gilead paid $11 billion in cash to buy biotech company Pharmasset for Sovaldi.

Gilead said on Friday an arbitration panel ruled in its favor, rejecting patent infringement claims from Roche Holding AG related to Sovaldi.

Achillion is expected to report data from an early-stage trial of ACH-3422 at the end of this year.

Nucs, which comprise the backbone of current hepatitis C treatment, work by blocking a protein needed by the hepatitis C virus to replicate.

Hepatitis C drugs have a history of being expensive, largely because some 170 million people worldwide have the often-fatal liver disease and do not have good treatment options.

Sovaldi costs $84,000 for 12 weeks of treatment.

Achillion said it would begin treating 12 additional patients for six weeks with a once-daily dose of ACH-3102 and sofosbuvir. [ID:nGNXVBIEVa]

The trial excluded the older hepatitis C drug ribavirin, which can cause rashes, anemia and other side-effects.

Achillion shares gave up most of their early gains and were up 8 percent at $9.13 on Friday morning on the Nasdaq. The stock touched an 18-month high of $9.94.

About 12 million shares changed hands by 11:00 a.m. ET, more than four times their 10-day average volume.

(Reporting by Anand Basu in Bangalore; Editing by Simon Jennings)
Reuters

Press Release

Achillion Achieves 100 Percent Sustained Virologic Response Rate (SVR4) From an Eight Week Phase 2 Trial Evaluating a Ribavirin-Free Regimen of ACH-3102 and Sofosbuvir for Genotype 1 HCV ("Proxy Study")

Achillion to Begin a Six Week Treatment Regimen With Its Second-Generation NS5A Inhibitor ACH-3102 and Sofosbuvir

NEW HAVEN, Conn., Aug. 15, 2014 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced interim results from an ongoing Phase 2 proxy study evaluating ACH-3102, Achillion's second-generation NS5A inhibitor, in combination with sofosbuvir, without ribavirin, for eight weeks of treatment in patients with treatment-naïve genotype 1 chronic hepatitis C virus (HCV) infection. Of the 12 patients treated, 100 percent (n=12/12) remained HCV RNA undetectable four weeks after completing therapy (SVR4). Based upon these results, 12 additional patients will begin treatment with six weeks of once daily ACH-3102 and sofosbuvir.

"ACH-3102 continues to demonstrate good safety and tolerability through three Phase 2 studies. We believe these studies also confirm a differentiated efficacy profile for an NS5A inhibitor. Achieving 100% SVR4 with eight weeks of treatment with sofosbuvir serving as a nucleotide proxy indicate that dosing 50 mg once daily of ACH-3102 plus a nucleotide inhibitor has the potential to achieve commercially competitive results for curing HCV in a short duration, ribavirin-free doublet," commented David Apelian, M.D., Ph.D., Executive Vice President and Chief Medical Officer at Achillion. "In addition, understanding how ACH-3102 performs with sofosbuvir provides valuable insight for the design of our proprietary combination trial with ACH-3102 and ACH-3422, a uridine-analog nucleotide that continues to advance through its Phase 1 clinical development program."

Milind Deshpande, Ph.D., President and Chief Executive Officer of Achillion commented, "As we continue to achieve clinical milestones, we remain focused on execution of the broader clinical development strategy for our HCV portfolio. We expect that Phase 1 proof-of-concept results with ACH-3422 will be reported during the fall of this year, which we anticipate will lead to the start of a Phase 2 combination program to evaluate our proprietary doublet regimen for an eight week, or potentially shorter, treatment regimen for HCV that will begin before the end of 2014."

ACH-3102 - 017: Phase 2 pilot study evaluating eight week treatment in combination with sofosbuvir for genotype 1 treatment-naïve HCV

Achillion is conducting a Phase 2, open-label, randomized, partial-crossover study to evaluate the efficacy, safety, and tolerability of eight weeks or six weeks of ACH-3102 and sofosbuvir, a marketed nucleotide polymerase inhibitor, without ribavirin, in treatment-naïve genotype 1 HCV-infected patients. The primary objective of the study is determination of sustained viral response 12 weeks (SVR12) after the completion of therapy. Eighteen patients were enrolled, including six observational patients. Twelve patients completed eight weeks of treatment consisting of 50 mg of ACH-3102 and 400 mg of sofosbuvir administered once daily while observational patients received no drug during this phase of the trial. Ten of the 12 patients receiving eight weeks of treatment had genotype 1a HCV with median HCV RNA at baseline of 7.22 log10 (range 5.5 - 7.8 log10). No on-treatment viral breakthrough or post-treatment viral relapse has been observed to date. ACH-3102 and sofosbuvir were well tolerated with no significant adverse events, ECG findings, or lab abnormalities observed during treatment.

Following achievement of the pre-specified response rate of 100 percent, the six observational patients plus six additional patients will be enrolled and receive six weeks of treatment consisting of 50 mg of ACH-3102 and 400 mg of sofosbuvir administered once daily. Achillion anticipates that SVR4 results from the crossover cohort will be reported by the end of 2014.

About HCV

The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 150 million people are infected with HCV worldwide including more than 5 million people in the United States. Three-fourths of the HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that can result in the development of liver cancer, liver failure or death.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's discovery, clinical development, and commercial teams have advanced multiple novel product candidates with proven mechanisms of action into studies and toward the market. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.

Cautionary Note Regarding Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the Company's expectations that the Phase 1 study of ACH-3422 could inform the potential initiation of combination studies of ACH-3422 and ACH-3102; the Company's expectations that it may report preliminary results from its Phase 1 program during the fall of 2014; the Company's plan to initiate a Phase 2 combination study of ACH-3422 with ACH-3102 by year-end 2014; the Company's goal to safely and expeditiously advance its all-oral regimens for the treatment of HCV and its expectation that the breadth of its portfolio could enable it to potentially develop commercially-competitive regimens that can be safe, effective, ribavirin-free and that can be used for eight weeks or less to potentially cure HCV. Achillion may use words such as "expect," "anticipate," "project," "intend," "plan," "aim," "believe," "seek," " estimate," "can," "focus," "will," and "may" and similar expressions to identify such forward-looking statements. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: demonstrate in any current and future clinical trials the requisite safety, efficacy and combinability of its drug candidates; advance the preclinical and clinical development of its drug candidates, including ACH-3422, ACH-3102 and sovaprevir, under the timelines it projects in current and future clinical trials; obtain and maintain necessary regulatory approvals; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; manage litigation; raise the substantial additional capital needed to achieve its business objectives; and successfully execute on its business strategies. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2013, and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any duty to update any forward-looking statement, except as required by applicable law.

http://ir.achillion.com/releaseDetail.cfm?ReleaseID=866418 

UK Recommends Covering Sovaldi Hepatitis C Pill

UK Recommends Covering Sovaldi Hepatitis C Pill

By Ed Silverman

WSJ

The U.K. agency that evaluates the cost effectiveness of prescription drugs has recommended the government pay for the controversial Sovaldi hepatitis C treatment, although not for all patients.

After reviewing the data, though, NICE agrees that Sovaldi is an effective improvement over existing treatments. The Gilead drug, by the way, can cure nine of 10 patients. The decision was likely helped by the lower price tag in the U.K. Gilead is selling its drug for about $56,000, according to a NICE spokesman. “It’s a lot cheaper here,” he tells us.

The agency is recommending Sovaldi, plus interferon and ribavirin, for adults with genotype 1, which is the most common form of hepatitis C, and accounts for 46% of all cases in the U.K., a NICE spokesman says. The recommendation also extends to patients with genotype 3, which accounts for 43% of hepatitis C sufferers (read the complete NICE document here).

Continue reading.... 

UK cost body backs pricey Gilead hepatitis pill for some patients
BY BEN HIRSCHLER

LONDON Fri Aug 15, 2014 5:06am IST(Reuters) - Gilead Sciences' expensive new hepatitis C pill has been endorsed for use in certain patients by Britain's healthcare cost-effectiveness watchdog, after the U.S. firm provided more information.

The National Institute for Health and Care Excellence (NICE) had told Gilead in June to come back with more data to support the use of Sovaldi, a drug whose sky-high U.S. price of $1,000 per pill has sparked fierce debate over costly modern medicines.

Carole Longson, director of the NICE Centre for Health Technology Evaluation, said on Friday it was now provisionally recommending Sovaldi, also known as sofosbuvir, as a cost-effective treatment for some people with chronic hepatitis C.

Gilead welcomed the decision to endorse Sovaldi as part of a combination treatment regimen, which it said would potentially make the drug available for the majority of hepatitis C patients.

The new drug is recommended for people chronically infected with certain strains, or genotypes, of the disease, which can cause liver cirrhosis and, in a small percentage of people, liver cancer. The conditions attached to its use vary according to a patient's disease state and any past treatments.

Gilead argues its drug's high price is justified by the near guarantee of a cure, far fewer side effects and the treatment's ability to help patients avoid far more expensive hospital treatment, including potential liver transplants.

But the sheer cost of the drug - which has already sold $5.8 billion in its first six months, making it the most successful new drug launch ever - has fueled controversy. Two members of the U.S. Senate Finance Committee wrote to Gilead last month asking the company to justify the price.

In Britain, where NICE's control over which drugs are used on the state health service exerts downward pressure on prices, Sovaldi is priced at 35,000 pounds ($58,400) for a 12-week course of treatment - 30 percent less than in the United States.

NICE was set up by the government in 1999 to decide in a rational way which drugs and treatments should be available on the National Health Service in England and Wales, making it an early pioneer of so-called healthcare technology assessment.

Since then it has had numerous run-ins with the pharmaceuticals industry, especially over cancer drugs.

The latest cancer drug row involves a decision, also announced on Friday, not to recommend the use of Johnson & Johnson's prostate cancer medicine Zytiga before chemotherapy, even though it is already recommended for use afterwards.

J&J said it was very disappointed by the ruling, which comes hard on the heels of a rebuff for Roche's new breast cancer drug Kadcyla last week.
(Editing by Raissa Kasolowsky)

Reuters

NICE backs Gilead’s Sovaldi in hepatitis C

But health watchdog denies earlier use of Janssen’s Zytiga

NHS patients in England received mixed news today as the region's health watchdog backed a new drug for use in hepatitis C but denied expanded use of another medicine in prostate cancer.

The National Institute for Health and Care Excellence (NICE), which provides guidance on the cost-effectiveness of medicines, issued draft guidance that recommends the use of Gilead Science's fast-growing Sovaldi (sofosbuvir) in people with chronic hepatitis C.

However, other draft guidance published today by NICE did not recommend changing the indication for Janssen's Zytiga (abiraterone) so that it can be used before chemotherapy in people with prostate cancer whose disease has spread.

The guidance for Sovaldi overturns a previous negative NICE decision for the revolutionary hepatitis C treatment, with the expert committee raising concerns about the cost of the drug, which has a UK list price of £35,983 (€45,041) or £69,966 (€87,575) depending on the length of treatment.

This reflected unease in the other countries such as in the US where politicians have questioned the $84,000 price for a 12-week course.

It appears Gilead has now provided extra data to appease NICE, with the agency stating that it has received “additional information about the drug's cost effectiveness from the manufacturer”.

Sovaldi is seen as a major advancement in hepatitis C treatment as it can shorten or remove the need for interferon-based therapy, a form of treatment associated with serious side effects.

This has led to huge uptake of the drug, despite its high price, with Gilead report revenues of nearly $6bn for Sovaldi in the first six months of 2014.

The NICE recommendation does not cover all hepatitis C patients, however, and Sovaldi is recommended in combination with peginterferon alfa and ribavirin in certain patients with genotype 1 and genotype 3 hepatitis C and in combination with ribavirin alone in certain patients with genotype 2 and genotype 3 hepatitis C.

Gilead commented: “While the draft recommendation will potentially grant access to sofosbuvir for the majority of hepatitis C patients, an unmet need still exists for those with specific sub-types of hepatitis C, who are not recommended for treatment with sofosbuvir under this draft guidance.”

No early use for Zytiga
Janssen had harsher words to say about NICE's final draft guidance that denied earlier use of oncology drug Zytiga in men with prostate cancer.

The drug was recommended in 2012 to treat castration-resistant metastatic prostate cancer, in combination with prednisone or prednisolone after a treatment cycle that included docetaxel.

However, Janssen is looking to move the drug further up the treatment pathway so it can be used prior to chemotherapy.

NICE recommends against this use in its latest guidance, with chief executive Sir Andrew Dillon claiming that the economic model provided by Janssen demonstrated that the drug “does not offer enough benefit to justify its price”.

Responding to this guidance Janssen's medical director for the UK Dr Peter Barnes said the decision “will leave thousands of men in England in the advanced stages of prostate cancer with no option but to accept chemotherapy - which they may not necessarily need or want yet”.

“These men will eventually be able to receive abiraterone on the NHS after chemotherapy anyway, but will be denied the option of taking it earlier on in their illness,” he added.

“Abiraterone is the second most requested medicine through the Cancer Drugs Fund and so the support for this treatment from doctors and patients is clear.”

In both cases final guidance is still to be issued by NICE.

Source

http://www.pmlive.com/pharma_news/nice_backs_gileads_sovaldi_in_hepatitis_c_592725

Gilead says wins favorable ruling on hep C drug Sovaldi

Gilead says wins favorable ruling on hep C drug

Aug 15 (Reuters) - Gilead Sciences Inc said an arbitration panel has ruled in its favor, rejecting patent infringement claims from Roche Holding AG, related to Gilead's hepatitis C drug, Sovaldi.

Roche initiated arbitration proceedings against Gilead in 2013, asserting exclusive rights over sofosbuvir by virtue of its 2004 collaboration agreement with Pharmasset Inc. Gilead bought Pharmasset in 2012.

Gilead started selling sofosbuvir under the brand name Sovaldi in December.

The arbitration panel on Thursday determined that Roche failed to establish any of its claims and is not entitled to any damages or other relief, Gilead said in a regulatory filing on Friday. (1.usa.gov/Xmtn2P)

Sovaldi, which costs $84,000 for 12-weeks of treatment, had sales of $3.5 billion in the second quarter ended June.

Gilead shares were up 1 pct in premarket trade. They had closed at $96.36 on Thursday on the Nasdaq. (Reporting by Shailesh Kuber; Editing by Sriraj Kalluvila)

Reuters