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Alan Franciscus
HCV Advocate
HBV Advocate

Drugs in Development / Clinical Trials—Updated August 19, 2014

Tuesday, August 19, 2014

Combination Treatment Tames HIV/HCV Coinfection

Sofosbuvir-based regimen ‘a quantum leap’ forward

Chicago—Patients coinfected with HIV and hepatitis C virus (HCV) who received combination therapy with sofosbuvir (Sovaldi, Gilead) and ribavirin had high rates of sustained HCV virologic response 12 weeks after discontinuation of therapy, according to a recent study in the Journal of the American Medical Association (JAMA 2014;312[4]:353-361).

The results are an encouraging development for the 7 million people worldwide who are thought to be coinfected with HIV and HCV, according to Mark S. Sulkowski, MD, a professor of medicine and medical director of the Viral Hepatitis Center at Johns Hopkins University in Baltimore.

“Hepatitis C is an important cause of morbidity and mortality among people living with HIV,” said Dr. Sulkowski, the lead investigator of the PHOTON-1 study.


Don't Get More Than Just a Tattoo

Spike in transmittable diseases tied to needle sharing

CINCINNATI —A public health initiative in Hamilton County to reduce the spread of diseases through needle sharing reports a quarter of its client base travels down from Butler County.

Libby Harrison, program manager at Cincinnati Exchange Project, said the advocacy agency opened its door in January in an effort to combat the spread of HIV and hepatitis C. The agency offers drug addicts a safe place for a one-to-one exchange of used syringes for clean syringes.

“People who come to us are already drug addicts,” Harrison said. “Our goal is disease prevention and to be happy to see them to build a sense of trust for when they’re ready for treatment.”

Read more....

Achillion Granted U.S. Patent for ACH-3102 and Structurally Related NS5A Inhibitors

NEW HAVEN, Conn., Aug. 19, 2014 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced that the U.S. Patent & Trademark Office has granted Achillion U.S. Patent No. 8,809,313, covering composition-of-matter and method of use claims for ACH-3102 and structurally related NS5A inhibitor compounds. ACH-3102 is Achillion's second generation Phase 2 NS5A inhibitor being investigated for the treatment of chronic hepatitis C virus (HCV) infection. This patent is entitled "Substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes useful for treating HCV infections," and provides a patent term which lasts until 2032.

"We believe that this key patent grant will provide another important anchor for Achillion's intellectual property portfolio. With the issuance of this patent for our differentiated NS5A inhibitor, ACH-3102, along with the previously granted patent for sovaprevir, our NS3/4A protease inhibitor, we are pleased to recognize the talented Achillion team that discovered and has advanced these compounds into Phase 2 trials evaluating their use in all-oral combination regimens for the treatment of chronic HCV," commented Milind Deshpande, President and Chief Executive Officer of Achillion.

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.

Read complete press release here...

Geisinger investigator nominated for federal award

Dr. Joseph Boscarino's research into disease that claimed his brother a major breakthrough 

DANVILLE, Pa., Aug. 19, 2014 /PRNewswire-USNewswire/ -- A Geisinger researcher on a personal crusade against hepatitis C has been nominated for a Centers for Disease Control and Prevention (CDC) award recognizing his unprecedented approach to addressing a major public health concern.

Joseph Boscarino, Ph.D. MPH, senior scientist, Geisinger Health System, is one of a team of researchers nominated for the Centers for Disease Control and Prevention (CDC) Charles C. Shepard Science Award for Data Methods and Study Design.

"Hepatitis C killed my younger brother in 2010, so finding a cure for this disease is very personal for me," Dr. Boscarino said. 

Monday, August 18, 2014

Review of the AASLD/IDSA/IAS–USA Guidelines, by Alan Franciscus: Epub ahead of print

  —Alan Franciscus, Editor-in-Chief

The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA/IAS-USA) recently issued revised guidelines:  The new section is titled, “When and in Whom to Initiate HCV Therapy,” and is part of the larger Recommendations for Testing, Managing, and Treating Hepatitis C.  The entire report can be viewed on our website.

The revised guidelines contain good news and bad news portions, but I think I get why these societies took this approach given the limited resources and high prices of the current standard of care drugs for treating hepatitis C.  More on this later; but first I would like to recap the recommendations.  I have also added my comments after each section of the recommendations. 

I would also like to disclose that I am an Associate Member of AASLD, but I have no insider information that would influence my comments.   

When and in Whom to Initiate HCV Therapy
“Successful hepatitis C treatment results in sustained virologic response (SVR), which is tantamount to virologic cure; virologic cure is expected to benefit chronically infected persons.  Limitations of workforce and societal resources may limit the feasibility of treating all patients within a short period of time.  Therefore, when such limitations exist, initiation of therapy should be prioritized first to those specific populations that will derive the most benefit or have the greatest impact on further HCV transmission.  Others should be treated as resources allow.”

First the good news:
“Treatment is assigned the highest priority for those patients with advanced fibrosis (Metavir F3), those with compensated cirrhosis (Metavir F4), liver transplant recipients, and patients with severe extrahepatic hepatitis C.”  

The tables referenced in the Recommendations list severe extrahepatic hepatitis C as certain kidney diseases (nephrotic syndrome or membranoproliferative), and Type 2 or 3 essential mixed cryoglobulinemia with end-organ manifestations (e.g., vasculitis).  (See “Patients First” in the August 2014 HCV Advocate for more information on extrahepatic manifestations.)
This is an appropriate and important recommendation.  People with advanced disease and severe extrahepatic disease need to be treated as soon as possible and should be treated regardless of resources or the price of the medications. 

Based on available resources, treatment should be prioritized as necessary so that patients at high risk for liver-related complications and severe extrahepatic hepatitis C complications are given high priority.”
This group includes:
  • Treating HCV in people who are HBV or HIV coinfected
  • People with another liver disease such as fatty liver disease, debilitating fatigue, diabetes, porphyria cutanea tarda (a severe skin condition) 
  • F2 fibrosis
This is where it gets confusing to me.  The recommendations list these categories as high priority, but only where resources are available.  I think this is contradictory.  In other words, treat if you can, but wait if the resources are not available.  Most likely this will be interpreted as ‘let’s wait.’  People who are coinfected with HIV or HBV, or coinfected with fatty liver disease, diabetes and porphyria and who are suffering from debilitating fatigue should really be given priority access to treatment regardless of resources available – resources should be made available.  I just can’t imagine a medical society making recommendations to defer treatment in people with these medical conditions.  But maybe I am taking the long view and the authors are looking at the short term – until other HCV medications are approved since we know that the approval is only months away?   

“Persons Whose Risk of HCV Transmission is High and in Whom HCV Treatment May Yield Transmission Reduction Benefits*”
  • MSM (men who have sex with men) with high-risk sexual practices
  • Active injection drug users
  • Incarcerated persons
  • Persons on long-term hemodialysis
*Patients at high risk of transmitting HCV should be counseled on ways to decrease transmission and minimize the risk of reinfection.

These are all populations that typically have very high rates of hepatitis C.  It stands to reason that by treating high risk people we can prevent the transmission of hepatitis C and decrease the prevalence.  But I’m still stuck on the ‘as resources are available’ portion of these recommendations. 

The bad news:
“Populations Unlikely to Benefit from HCV Treatment”

“Patients with limited life expectancy for whom HCV therapy would not improve symptoms or prognosis do not require treatment.  Chronic hepatitis C is associated with a wide range of comorbid conditions.  (Butt. 2011): (Louie, 2012).  Little evidence exists to support initiation of HCV treatment in patients with limited life expectancy (less than 12 months) due to non-liver-related comorbid conditions.  For these patients, the benefits of HCV treatment are unlikely to be realized, and palliative care strategies should take precedence.  (Holmes, 2006); (Maddison, 2011)”

I included this in the article because we know that hepatitis C causes non-liver related deaths – one study estimated that hepatitis C reduced survival by more than 20 years.  Unfortunately, these recommendations will only create more apathy among medical professionals, government officials, and society in general and lead to even more people dying from hepatitis C and from hepatitis C non-liver related deaths.   

Editorial comment
At first I was baffled and very angry with these recommendations.  We have medications that are approved by the Food and Drug Administration that have cure rates up to 90%, with tolerable side effects and shorter treatment durations.  Medical societies generally put the health of patients and society before political, monetary or any other concerns.  But after reading the recommendations over and over and especially reading the following section I think I get what was driving the recommendation:
“Limitations of workforce and societal resources may limit the feasibility of treating all patients within a short period of time.”

The two medications that are the current standard of care are sofosbuvir (Sovaldi) and simeprevir (Olysio), which cost $80,000 and $66,000 respectively and that is not counting any other medications that might be included.  The pricing of the drugs, especially sofosbuvir, has caused uproar within the press and the government, among advocates  and insurance companies and just about anyone else who has heard about the pricing.  Some insurance companies are refusing to cover it.  State Medicaids are refusing to provide coverage except to the sickest patients.  Medicare is worried it will be bankrupted by sofosbuvir.  Insurance companies are telling us it is going to cost every insured American $100 to $200 more every year on premiums.  Politicians are holding meetings demanding to know why it is priced so high.  Advocates are demonstrating.  Scare tactics – definitely, but some of these are valid concerns. 

Within a very short time, we will have two new HCV therapies approved by the FDA—combination therapies from Gilead and AbbVie.  Not long after these two drugs are approved others will follow from BMS and Merck, and there are even more drugs in the pipeline.  Typically, when new drugs are marketed the new prices are even higher than the older drugs.  Unfortunately, in this country there are no agencies that can set or limit the price of a drug – at least not yet.   

AASLD/IDSA can’t negotiate or limit drug prices, but they can issue guidelines.  In the case of the latest medications, insurance companies and government agencies have limited access to the medications because of the price, and must allocate limited resources among a great number of patients.  I think this is what AASLD/IDSA is doing with their latest guidelines.  In other words, since the price is so steep and since there are limited resources we cannot recommend treatment for everyone.  I think they are also saying that if you develop a new drug and don’t price it reasonably, considering actual societal resources, we are going to have to take a good hard look at it before we recommend it to everyone with hepatitis C.  I believe they are also sending a message to pharmaceuticals that if you want to sell your drugs to the masses you will have to invest in “societal resources,” not just dump your expensive drugs into the marketplace.The government also has to do its part to address hepatitis C – develop comprehensive resources like there are for HIV, diabetes, cancer, etc.  

This is my take on the recommendations.  I really hope that I am right and that this is not another elitist group making recommendations.  I do hope that the drug companies and the government are paying attention.  The next round of drug approvals, pricing, resources allocated to hepatitis C and the next recommendations will show the truth.  There are literally millions of lives that can be saved and billions of dollars to be made as long as appropriate resources can be devoted and drugs can be sold at prices that will be translated into treatment for everyone with hepatitis C. 

One last thing.  Even if this is the message that the medical societies are trying to convey, I think there is something terribly wrong with limiting treatment to only those who are the sickest of the sickest.  People with hepatitis C deserve more compassion and care.    

UK's NICE Recommends Gilead's Sovaldi For Hepatitis C

The National Institute for Health and Care Excellence (NICE) in the U.K. announced in a press release that it has recommended Gilead’s Sovaldi (sofosbuvir) for Hepatitis C treatment. The medication has been under intense scrutiny due to its high cost of $84,000 for a 12-week regimen. The Wall Street Journal reports that NICE often denies financial coverage for medications and “often butted heads with drug makers and patient groups over its decisions.” After asking Gilead for more information, the U.K. agency decided that Sovaldi was an improvement over existing treatments, and the selling cost of $54,000 in the U.K. may have swayed its decision.

Details are available in the NICE Appraisal Consultation Document. The agency says that Sovaldi, plus interferon and ribavirin, is for adults with genotype 1, which accounts for 46 percent of the Hepatitis C patients in the U.K. The treatment also extends to patients with genotype 3, accounting for 43 percent of patients.

However, NICE’s recommendation does not allow coverage for patients with genotype 1. This decision was made upon NICE’s measurement of the quality of patients’ remaining years while taking a medication and the cost to attain that quality. For this subgroup, Sovaldi’s cost-effectiveness was $80,000.