AASLD - Achillion to Present HCV Data on ACH-3102/Sofosbuvir and Preclinical Profile of ACH-3422

Achillion to Present Updated Clinical HCV Data on ACH-3102 and Preclinical Profile of ACH-3422 at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting

- Late breaker poster presentation will feature updated SVR results from the Phase 2 trial of ACH-3102, NS5A inhibitor, plus sofosbuvir for the eight-week treatment of genotype 1 HCV -

- Three preclinical posters on ACH-3422, uridine-analog nucleotide prodrug, to be presented –

NEW HAVEN, Conn., Oct. 8, 2014 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq: ACHN) today announced four abstracts have been accepted for presentation at The Liver Meeting® 2014, the 65th Annual Meeting of The American Association for the Study of Liver Diseases (AASLD), in Boston, November 7 – 11.

A late breaker poster presentation will be made providing updated results, including SVR12, 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. This trial is currently dosing patients in a follow-on six-week treatment cohort.

Furthermore, three additional posters will be presented detailing the preclinical profile of ACH-3422, a uridine-analog nucleotide that continues to advance through its Phase 1 clinical development program.

David Apelian, M.D., Ph.D., Executive Vice Present and Chief Medical Officer, commented, "We are delighted that Achillion's ongoing research into HCV with ACH-3102 will be featured in a late breaker poster presentation during the 2014 Liver Meeting. Furthermore, as we work to complete the Phase 1 trial of ACH-3422, we are pleased to have the opportunity to present new preclinical research detailing the profile of ACH-3422."

Publication No. LB-23

Title: Interim sustained virologic response (SVR), safety and tolerability results of 8-week treatment with ACH-3102 and sofosbuvir in chronic hepatitis C (HCV), genotype-1 (GT-1), treatment-naïve patients: a Phase 2 "proxy" study

Authors: E. Gane, H. Kocinsky, C. Schwabe, et al.

Date/Time: Monday, November 10th, 8:00 a.m. - 5:30 p.m. ET.

Session: Late-Breaking Poster Session

Room: John B. Hynes Convention Center, Hall C

Publication No. 1978

Title: ACH-3422, a novel HCV NS5B RNA polymerase nucleotide inhibitor, demonstrates improved potency over sofosbuvir against HCV genotype-3 replicons in vitro

Authors: Y. Zhao, S. Podos, J. Fabrycki, et al.

Date/Time: Tuesday, November 11th, 8:00 a.m. – 12:00 p.m. ET.

Session: Hepatitis C: Preclinical Development Poster Session

Room: John B. Hynes Convention Center, Hall C

Publication No. 1982

Title: A novel approach to HCV resistance selection featuring short treatment duration and reduced interference from host cell adaptation

Authors: J. Fabrycki, Y. Zhao, D. Patel, et al.

Date/Time: Tuesday, November 11th, 8:00 a.m. – 12:00 p.m. ET.

Session: Hepatitis C: Preclinical Development Poster Session

Room: John B. Hynes Convention Center, Hall C

Publication No. 1985

Title: Antiviral activity and resistance emergence: combinations of the NS5B nucleotide inhibitor ACH-3422 with other antiviral agents in vitro

Authors: D. Patel, Y. Zhao, J. Fabrycki, et al.

Date/Time: Tuesday, November 11th, 8:00 a.m. – 12:00 p.m. ET.

Session: Hepatitis C: Preclinical Development Poster Session

Room: John B. Hynes Convention Center, Hall C

Additional information including the date and time of presentations are provided below. Reprints of the posters will be made available on the Company's website at www.achillion.com/resources and accessible after presentation at AASLD.

Sovaldi - What Can We Learn from Recent Hepatitis C Treatments?

What Can We Learn from Recent Hepatitis C Treatments?

Published on Oct 2, 2014

On October 1, the Engelberg Center for Health Care Reform and the USC Schaeffer Center for Health Policy and Economics hosted a half-day forum to discuss the serious coverage challenges that accompany breakthrough treatments, such as the much-discussed new treatment for Hepatitis C, Sovaldi.

Links:
Reducing the cost of new hepatitis C drugs
An index of articles pointing the reader to the current controversy over the high price of Sovaldi.

Hepatitis C Linked To Higher Risk of Coronary Artery Disease

Hepatitis C Linked To Higher Risk of Coronary Artery Disease

MedicalResearch.com 

Interview with:
Naga Pothineni, MD
Division of Cardiology
University of Arkansas for Medical Science

MedicalResearch: What are the main findings of the study?

Dr. Pothineni: Hepatitis C is a blood borne infection that is very common worldwide. Most pateints who contract hepatitis C develop a chronic form on infection that progresses to liver damage and eventually hepatocellular cancer. Coronary heart disease is a worldwide problem as well. There has been interest in chronic infections being a mechanism of progression of atherosclerosis and coronary heart disease. We wanted to study the association of coronary heart disease events in patients with hepatitis C. We conducted a retrospective study of around 24,000 patients of which around 10,000 were hepatitis C positive. Our study showed that patients who have hepatitis C have a higher incidence of coronary heart disease events (myocardial infarction) when compared to patients who are negative for hepatitis C. In our analysis, we found that hepatitis C positivity is an independent risk factor for coronary events after adjusting for traditional cardiovascular risk factors like age, hypertension, smoking and diabetes.

Another interesting finding in our study was that patients with hepatitis C have lower levels of cholesterol compared to patients without hepatitis C. Low cholesterol levels in these patients do not seem to be protective against future coronary heart disease events.

MedicalResearch: What was most surprising about the results?

Dr. Pothineni: A novel and surprising result in our study was that patients with persistent (active) hepatitis C infection have higher incidence of coronary heart disease events compared to patients who have remote or treated infection.

Some patients who have hepatitis C spontaneously clear their infection by the natural immune responses. Those that fail to do so appear to be at a higher cardiovascular risk

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Pothineni: Clinicians should be aware of hepatitis C being a potential cardiac risk factor. Active infection can be detected by checking for hepatitis C RNA levels. It might be reasonable to aggressively control traditional cardiovascular risk factors in patients with active infection to decrease the incidence of coronary heart disease events in this population

MedicalResearch: What recommendations do you have for future research as a result of this study?

Dr. Pothineni: Treatment for hepatitis C has advanced tremendously and it is now possible to achieve cure. Future research can show us if treatment of hepatitis Cwith the currently available therapies can help decrease cardiovascular risk in these patients.

Citation:

Impact of Hepatitis C Seropositivity on the Risk of Coronary Heart Disease Events Pothineni, Naga Venkata et al. American Journal of Cardiology

Bristol-Myers withdraws FDA NDA for asunaprevir

Bristol-Myers pulls U.S. marketing application for hepatitis C treatment
Oct 7 (Reuters) - Bristol-Myers Squibb said it withdrew its U.S. marketing application for a drug combination to treat hepatitis C.

The drugmaker will continue to pursue marketing approval of daclatasvir, one part of the combination, the company said in a statement.

Bristol-Myers said the combination treatment of daclatasvir and asunaprevir was approved in July for use in Japan.

Bristol-Myers Squibb Statement about Asunaprevir in the U.S.

PRINCETON, N.J.--(BUSINESS WIRE)--

Given the rapidly evolving hepatitis C (HCV) treatment landscape in the U.S., Bristol-Myers Squibb (BMY) has decided that it will not pursue U.S. Food and Drug Administration (FDA) approval of the dual regimen of daclatasvir and asunaprevir for the treatment of HCV genotype 1b patients in the United States and has therefore withdrawn its new drug application (NDA) for asunaprevir, an NS3/4A protease inhibitor. The company will continue to pursue FDA approval of daclatasvir, a potent, pan-genotypic NS5A complex inhibitor (in vitro), which is currently being investigated globally in multiple treatment regimens for HCV patients with high unmet need.

Bristol-Myers Squibb’s HCV strategy has always been to focus on the unique unmet medical need of each local market. For example, in Japan we were pleased to receive regulatory approval for the dual regimen of daclatasvir and asunaprevir in July, bringing Japanese patients with HCV the first all-oral, interferon- and ribavirin-free treatment regimen.

The dual regimen was developed to meet the distinct need of the Japanese patient population, and we believe this treatment has the potential to play a major role in curing HCV patients in Japan, as well as in other markets where the HCV patient population is similar to Japan. In the EU, daclatasvir was recently approved for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of HCV infection in adults. Similarly, we believe that daclatasvir-based regimens have the potential to fill continued unmet medical need in the U.S. and elsewhere in the world.

We plan to submit additional data for daclatasvir to the FDA from our ongoing clinical trial program focused on difficult-to-treat patients, including patients with HCV genotype 3, patients who are pre- and post-liver transplant, and patients co-infected with HIV. Next month at the annual meeting of The American Association for the Study of Liver Diseases (AASLD), we will present new data from several daclatasvir-based regimens. We look forward to bringing daclatasvir to patients in the U.S. and will continue to work closely with the FDA to advance our regulatory application, with the aim of bringing the investigational product to market as quickly as possible. 

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Sovaldi - How Some State Medicaid Programs Limit Drugs to Only the Sickest Patients

Related:
Medical roller coaster of hepatis C treatment
So she received insurance approval for the expensive dual-drug combination of sofosbuvir and simeprevir, which she took May through July, with a $10,000 copay and a total medication cost of $144,000, she said. And it worked. Since her blood test in July, she has had no signs of infection...

How Some State Medicaid Programs Limit Drugs to Only the Sickest Patients

BY STATELINE | OCTOBER 6, 2014

By Michael Ollove

The new hepatitis C drug Sovaldi promises a cure rate of well over 90 percent, compared to 45 percent (at best) for older drugs. But when Sovaldi went on the market earlier this year for as much as $84,000 for a single course of treatment, critics blasted the cost as “exorbitant” and “gouging.”

It is estimated that between 3.2 million and 5.2 million Americans have hepatitis C, an infectious illness that can eventually compromise the liver.

The disease falls disproportionately on the poor and the incarcerated, which makes it a particular challenge for Medicaid, the federal-state health plan for the poor, and for state prison systems. One study by Express Scripts, a drug benefits management company, estimated it would cost states $55 billion to provide Sovaldi to all prisoners and Medicaid beneficiaries with hepatitis C.

Because of its high cost, some state Medicaid programs and prison systems are refusing to provide Sovaldi to any but the sickest patients. Most recently, Oregon last month threatened to limit access to the drug unless it can get Sovaldi at a deeply discounted price.

“Sovaldi is a seminal event,” said Matt Salo, executive director of the National Association of Medicaid Directors. “It’s clear that states are not equipped to handle this. They simply do not have the tools to maintain control.”

But Sovaldi is only the beginning. Expensive new treatments for certain cancers, rheumatoid arthritis and other conditions also have rattled Medicaid officials, patients and health care providers.

What can states do to hold down drug costs? 

Drug pricing is a complicated and opaque process. Here are some of the basics.
Is each state Medicaid program on its own when it comes to drug pricing?

Not completely. The federal Omnibus Budget Reconciliation Act of 1990 mandates that drug makers give all Medicaid programs a 23 percent rebate off the Average Manufacturers Price (AMP) for all prescription drugs purchased, or the difference between the AMP and the best price given to a private payer. (Prisons aren’t covered by this discount provision and have to negotiate drug prices as any retailer does.)

In return for the rebates, Medicaid programs must carry all drugs approved by the U.S. Food and Drug Administration on their “formularies,” which is the list of the medications each health plan will pay for. That guarantee means that the drug makers get access to substantial markets in all 50 states and the District of Columbia.

But even with the 23 percent discount, drugs are unusually expensive in the U.S., which unlike other Western nations has no price controls on drugs. In 2013, for example, the cost of the reflux medicine Nexium ranged from $23 to $60 in the Netherlands, England, Spain and Switzerland, but averaged $215 in the U.S., according to the International Federation of Health Plans.

Why doesn’t the U.S. have price controls on drugs?

The short answer is America’s strong belief in the free market’s capacity for fostering innovation. Price controls, the pharmaceutical industry argues, would discourage the high-risk investment that drug makers need to develop breakthrough cures and treatments.

The cost of nurturing a single drug from the laboratory to the market is generally well over $1 billion. And the odds are stacked heavily against any single drug making it: Only about one in 5,000 drugs that enter preclinical testing ultimately receives approval for sale by the U.S. Food and Drug Administration. Even getting through human clinical trials hardly guarantees ultimate success, since only about one fifth of those drugs make it to the market. Drugs that reach the market take an average of 12 years to do so.

Other than the rebate, is there any other way state Medicaid programs can control their drug costs?

States can negotiate for supplemental rebates.

How does that work?

For many health conditions, patients (or their doctors) have several choices of which drug to use. For instance, not long ago, the cholesterol-fighting drugs Lipitor, Zocor and Crestor were among a number of cholesterol-fighting drugs on the market at the same time. (Patents on the first two expired in recent years.)

A prescription health plan, including a Medicaid program, can show a preference for one drug over another by putting it on its Preferred Drug List. Drugs that don’t make it on that list are subject to obstacles that dissuade patients (and their doctors) from their use. In Medicaid, those obstacles are co-pays and requirements for prior authorization from the health plan. For obvious reasons, drug makers are eager to get their products on preferred drug lists, and they are willing to pay for their inclusion. That creates negotiating room for the state Medicaid programs.

How large are these discounts?

Negotiations on supplemental rebates are confidential, because pharmaceutical companies consider pricing considerations proprietary. As a result, states cannot band together and demand deeper discounts.

In the case of Sovaldi, can’t the Medicaid programs use the preferred drug lists to get better rebates?

In this case, no. There is no preferred drug list when a new drug essentially creates a class of its own. Sovaldi is a breakthrough drug, far superior to what came before. Because it has no competitor, the states have little leverage.

So the Medicaid plans are helpless?

Not entirely. Through the prior authorization process, they can essentially ration the use of Sovaldi, which is what a number of state Medicaid plans and prison systems are doing. They are saying that only patients with advanced symptoms are eligible for Sovaldi. So even though a cure is available, many of those with the hepatitis C virus will be unable to get it. However, patients who are denied coverage for the drug may go to court to insist on access.

So how will states deal with other expensive breakthrough drugs?

Sovaldi certainly represents close to a worst-case scenario in terms of pricing. It is a breakthrough drug for a widespread, life-threatening condition. Many other expensive breakthrough drugs are for rarer conditions. Still, many believe that price controls of some kind are inevitable if drug manufacturers don’t moderate prices on their own.

Some have suggested a value-based pricing system tying drug prices to two measures of benefit: the clinical value of the drug, measured in quality-adjusted years of life gained through its use; and the cost savings associated with the use of the drug. In the case of Sovaldi, that would include the cost of liver transplants that no longer would have to take place.

Read more....

Weekend Reading; Friday, anticipated date for FDA decision on Gilead's ledipasvir/price? And our hep hero

Hello everyone, welcome to Weekend Reading, getting ready for Autumn? No doubt you have a few outside chores to finish up, me too.

Annual Meeting of the American Association for the Study of Liver Diseases

Next month the 65th Annual Meeting of the American Association for the Study of Liver Diseases will take place in Boston, the liver meeting will begin on November 7th, and end on November 11th.

Late-breaking abstracts now available

Hep Hero - Fall Newsletters

Lucinda K. Porter, RN

Readers, you are in for treat, Tim Murphy writes about our devoted HCV advocate, Lucinda K. Porter, RN., in his article; Hep Hero, published online at HepMag.com. 

Hep is an award-winning print and online brand for people living with and affected by viral hepatitis. Offering unparalleled editorial excellence since 2010, Hep and HepMag.com are the go-to source for educational and social support for people living with hepatitis.

In this months issue

Click here to read digital edition

Hep Hero

by Tim Murphy

How one woman overcame hepatitis C and ended up helping others fight it, too.

Eye of the Tiger
by Oriol R. Gutierrez Jr.
The potential for up to millions of Americans to benefit from the new hep C meds makes this one of the most exciting moments in modern medicine.

Sovaldi-Ledipasvir Pill Safe With Major HIV Meds
by Benjamin Ryan
Gilead Sciences’ fixed-dose combination pill of Sovaldi (sofosbuvir) and the investigational ledipasvir, likely to receive FDA approval on October 10, does not significantly interfere with five common HIV antiretrovirals.

'3D' Cures 99% to 100% of Genotype 1b
by Benjamin Ryan
AbbVie’s so-called “3D” combo regimen ditched ribavirin and still cured 99 percent to 100 percent of study participants with genotype 1b of hepatitis C virus (HCV) in two recent Phase III trials.

Daclatasvir and Asunaprevir Cure Up to 87% of 1b
by Benjamin Ryan
Bristol-Myers Squibb's daclatasvir and asunaprevir cured 81 percent to 87 percent of people with genotype 1b of hepatitis C in a recent Phase III trial.

Primary Care Docs Clueless About Hep C Drugs
by Benjamin Ryan
About three out of four primary care physicians (PCPs) are unfamiliar with the new generation of hep C drugs which received U.S. Food and Drug Administration (FDA) approval at the end of 2013.

Hep C Suppression Linked to Major Health Benefits
by Benjamin Ryan
Suppressing the hep C viral load is associated with a diminished risk of liver disease and death.

Curing Hep C Lowers Central Nervous System Fatigue
by Benjamin Ryan
Ridding the body of hep C reduces central fatigue, which is weakness originating in the central nervous system. 

Connect With Us On Twitter and Facebook

 

HCV Advocate

The HCV Advocate newsletter is a valuable resource designed to provide the hepatitis C community with monthly updates on events, clinical research, and education.

HCV Advocate News & Pipeline Blog
Click Here

HCV Advocate October Newsletter
Click Here

In This Issue:


Alan Franciscus, Editor-in-Chief
In this month’s column, I will provide a short overview of phase 3 data from sofosbuvir plus ledipasvir. It is important to know, however, that when approved the FDA may add or change the cure rates and add additional warnings or restrictions to the use of the medications based on their review of the clinical trial data. 

Read more...


Lucinda K. Porter, RN
This month, Lucinda discusses the AASLD and IDSA’s recommendations assigning high treatment priority to those with high risk of HCV transmission. When we reduce HCV transmission, we reduce the prevalence, which benefits us all.

Read more...


Alan Franciscus, Editor-in-Chief
One of the most important decisions that anyone with hepatitis C (HCV) will make is about HCV treatment. In the past, it has been a difficult decision because of the significant side effects, long treatment duration and modest cure rates. 

Read more...


Lucinda K. Porter, RN
Lucinda reviews studies on depression and HCV disease progression, mother-to-child transmission, healthcare utilization and racial differences in progression to cirrhosis and HCC. 

Read more...

Website Plan & Survey Report
Alan Franciscus, Editor-in-Chief

Find out what the results of our recent survey were; what we are going to do about them, and who won the autographed copy of Lucinda's book Hepatitis C One Step at a Time. 

Read more...

Connect With HCV Advocate

 

Stay safe, enjoy the weekend

Tina

Sofosbuvir/Ribavirin - Researchers Set to Study Hepatitis C Therapy in Children

Researchers Set to Study Hepatitis C Therapy in Children
Eileen Oldfield, Associate Editor

Published Online: Saturday, October 4, 2014

Researchers from Saint Louis University Medical Center will test the safety and efficacy of sofosbuvir and ribavirin in children with hepatitis C. 

The all-oral regimen will be tested in children aged 3 to 17 with a goal of curing hepatitis C without the flu-like side effects seen with traditional therapies. “Many times patients would be on the traditional medication but quit within a year,” said principal investigator Jeffrey Teckman, MD, in a press release. “It’s a cure rate of 50%. 

The new study will consist of all-oral medication. That would mean no shots or flu-like side effects, and also much shorter course of treatment.” The FDA approved the all-oral medication regimen in 2013. More than 95% of patients achieved cure rates in clinical trials for the drug, and very few patients discontinued the therapy. 

Furthermore, a study published in the April 2014 edition of Journal of Hepatology suggests that sofosbuvir therapy impacts patients’ health-related quality of life less than traditional interferon regimens. Researchers hope to see similar results in children, although their main aim is to determine whether side effects are as low in children as in adults. 

The researchers will also investigate whether children will need extra time for the therapy to work. “I think this treatment is a real game changer,” Dr. Teckman said. “The previous treatments were arduous. People would often start the treatment, but eventually drop out. This new therapy is a revolution that affects people around the world.” Despite the adherence success seen in clinical trials, a recent study by the CVS Health Research Institute suggests that higher rates of patients are dropping off of sofosbuvir therapy, particularly if the patients were new to any hepatitis C treatment. 

The analysis found discontinuation rates of 8.1% overall, with discontinuation rates of 8.7% in patients who were not previously treated for hepatitis C. The high price tag for sofosbuvir therapy tag has come under fire as well. Teckman believes the study will close the gap between pediatric and adult medical research. “A lot of times, studies for children don’t get approved,” Dr. Teckman said. “The exciting part with our study is that the medication has already been tested in adults, and we are moving rapidly to test it in children.”

Source

Related

Sofosbuvir/Ribavirin - Adolescents and Children

Recruiting
Safety and Efficacy of Sofosbuvir + Ribavirin in Adolescents and Children With Genotype 2 or 3 Chronic HCV Infection

Conditions: Hepatitis C Virus Infection
Drug: SOF
Drug: RBV
Phase 2
ClinicalTrials.gov Identifier: NCT02175758

Ledipasvir/Sofosbuvir - Adolescents and Children

This study is not yet open for participant recruitment
Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination in Adolescents and Children With Chronic HCV-Infection

Condition: Hepatitis C Virus Infection
Drug: LDV/SOF
Phase 2
ClinicalTrials.gov Identifier: NCT02249182

View Additional Trials

Upcoming/Recruiting HCV Clinical Trials - Sofosbuvir Based Including Ledipasvir/Sofosbuvir

 

Be Hip To Hep: Dispelling old myths and discovering the hopes for those with hepatitis C

Be Hip To Hep: Dispelling old myths and discovering the hopes for those with hepatitis C

Good morning folks, over at DentistryIQ an insightful article about living with hepatitis C now available for your reading pleasure.

Dr. Muñoz, professor of English at Cosumnes River College writes from a patients perspective about living with HCV.

The article offers information about; diagnosis, transmission/sexual transmission, risk factors, blood tests, stigma - "In addition to work difficulties, my personal life disintegrated. I felt a sense of shame as I listened to a friend unwittingly joke how Pamela Anderson was repulsive. Not because of her famously exaggerated cup size, but rather (and solely) because she had the misfortune of contracting HCV." as well as treatment, and advice for persons living with the virus.

Be hip to hep

Dispelling old myths and discovering the hopes for those with hepatitis C

BY HEIDI EMMERLING MUÑOZ, PhD

"You have hepatitis C."

Those words turned my life upside down. I tell this story not to elicit sympathy but to illustrate what it means to live with hepatitis C (HCV): the physical as well as the emotional. Only now, because I am out of clinical hygiene and because there is a cure in sight, do I feel safe in telling my story.

I also tell this story to urge screening and to give hope to anyone living with HCV.

Continue reading....