Get Tested. Get Treated. Get Cured. - HCV...

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Get Tested. Get Treated. Get Cured.OCTOBER 2016 Vol. 19, Issue 10

— CONTINUED ON PAGE 2

—Alan Franciscus, Editor-in-Chief

In this month’s column, I discuss the results from two clinical studies: the first report is about a Phase 2a study of the combination of three drugs to treat and cure hepatitis C (HCV) genotype 1 in 6 to 8 weeks. The second one is a study on a triple therapy of drugs to treat and cure hepatitis C in as little as three weeks by response guided therapy! The common thread of both studies is that they have the potential to decrease the length of treatment and perhaps increase the cure rate.

Odalasvir+AL-335+Simeprevir In a press release from Achillion Pharmaceuticals, Inc., the Phase 2a study results were announced. The goal of the study was to understand the safety and to determine an

effective dose of the combination of odalasvir, AL-335 with and without simeprevir to treat HCV genotype 1 treatment-naïve patients. Listed in the table below are the results.

AL-335 Odalasvir Simeprevir Duration Cure rates400 mg QD 50 mg QD 100 mg QD 8 weeks 100% (20 of 20 pts)800 mg QD 50 mg QOD none 8 weeks 90% (18 of 20 pts)800 mg QD 50 mg QOD 75 mg QD 8 weeks 100% (20 of 20 pts)800 mg QD 50 mg QOD 75 mg QD 6 weeks 100% (20 of 20 pts)QD = once daily; QOD = every other day

The combination of drugs was safe and well-tolerated. The most common side effects were headache, fatigue and an upper respiratory tract infection. There was one serious adverse event that resolved when treatment ended. Based on the results of this trial, the combination of odalasvir (25mg), AL-335 (800 mg), and simeprevir (75 mg) is being advanced into Phase 2b studies. The clinical development of these drugs will eventually be expanded to treat genotypes 1, 2, 3, 4, 5 and 6. The clinical trials identifier is NCT02765490 on

www.clinicaltrials.gov. The trial is listed as active, but it is not currently recruiting patients. When it becomes active it will be listed on HCV Advocate Clinical Trials Reference Guide – http://hcvclinical.hcvadvocate.org/ Editorial CommentsThe difficult task is to achieve a 100% cure rate with a short treatment duration when and if it enters into Phase 3 clinical trials.

IN THIS ISSUESnapShots 3Healthwise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5Under The Umbrella . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7Drug Pipeline 10What’s Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

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Is this the new blockbuster HCV therapy? The bar now is set so high that an HCV drug has to have high cure rates, low side effects and have ease of use. The cost of a new drug is another important factor to bring a blockbuster HCV drug to market. Still, we need more HCV medications to treat hepatitis C, so that people living with hepatitis C have more treatment choices. I’m pulling for this combination to make it! Source: Achillion Press Release 3-Week Response-Guided TherapyAn important study was recently published in Lancet Gastroenterology & Hepatology. The study—Efficacy and safety of 3-week response-guided Triple direct-acting antiviral therapy for chronic hepatitis C: a phase 2, open-label, proof-of-concept study—holds the promise of changing the way that people with hepatitis C are treated. The study evaluated a 3-week treatment duration of a combination of HCV medications. Patients were enrolled between April 05, 2015 and April 15, 2015. All of the 26 patients enrolled in the study were HCV genotype 1b treatment naïve without cirrhosis. The patients were randomly assigned to three treatment groups. • Twelve patients were treated with sofosbuvir, ledipasvir

and asunaprevir; • Six patients were treated with sofosbuvir, daclatasvir

and simeprevir; • Eight patients were treated with sofosbuvir, daclatasvir

and asunaprevir. Note: Ultrarapid virological response is defined as less than 500 IU/mL HCV RNA or viral load at day 2 of treatment. Six patients in each group achieved an ultrarapid virological response. Patients who achieved an ultrarapid virological

response were continued on their current medications for a total of 3 weeks. The patients who did not achieve an ultrarapid virological response by day 2 were switched to sofosbuvir plus ledipasvir for either 8 or 12 weeks. All of the patients who achieved the ultrarapid virological response who received 3 weeks of treatment were cured. The patients are still being followed and as of March 2016 there has not been any adverse events or treatment-related relapse. The most common side effects in all of the 3-week patient groups were fatigue and headache. There were no serious side effects. Editorial Comments:This was presented at the Liver Conference 2015, but little information was provided. Now that it is published in a prestigious journal—The Lancet—it provides more information and credibility. The current group of scientists is planning a larger study in Mongolia. I hope this approach is being studied elsewhere including the United States. It could have the potential to reduce the treatment duration, lower the side effects, improve drug adherence and greatly reduce the cost of therapy. A couple of caveats: 1. Genotype 1b is one of the easiest genotypes/subtypes

to cure. This approach—or a similar approach—needs to be studied in other genotypes/subtypes.

2. This is a small proof of concept clinical trial. There is a need for larger studies with a diverse patient population.

Source: Efficacy and safety of 3-week response-guided triple direct-acting antiviral therapy for chronic hepatitis C infection: a phase 2, open-label, proof-of-concept study—G Lau et al. Volume 1, Issue 2, October 2016, Pages 97–104

— CONTINUED FROM PAGE 1

Alan Franciscus is the Executive Director of the Hepatitis C Support Project and

the Editor-in-Chief of the HCV Advocate Website.

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Article: Effectiveness of Sofosbuvir, Ledipasvir/Sofosbuvir, or Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir Regimens for Treatment of Patients With Hepatitis C in the

Veterans Affairs National Health Care System—GN Ioannou et al. Source: Gastroenterology. 2016 Sep;151(3):457-471.e5. doi: 10.1053/j.gastro.2016.05.049. Epub 2016

Study Aims and ResultsThe study authors reviewed records from January 01, 2014 through June 20, 2015 of 17,487 hepatitis C (HCV) patients treated at the Veterans Affairs National Health Care System. Of these, 13, 974 were HCV genotype 1; 2,131 were genotype 2; 1,237 with genotype 3 and 135 with genotype 4. The treatment regimens (with and without ribavirin) con-sisted of sofosbuvir (Sovaldi - 2,986 patients); ledipasvir/sofosbuvir (Harvoni – 11,327 pts); Viekira Pak (3,174 pts). Genotype 1: Among the patients who were treated with Harvoni or Viekira Pak the cure rates were 92.8% in genotype 1. The cure rates between Harvoni and Viekira Pak were similar. Genotype 2: Treatment with Sovaldi plus ribavirin re-sulted in a 86.2% cure rate. Genotype 3: The most effective treatment was the combination of Sovaldi, pegylated interferon plus ribavirin (87%) followed by Harvoni plus ribavirin (77.9%). Genotype 4: There were various combination of drugs given to genotype 4 patients. The cure rates ranged from 89.6% to 93.5%

Note: the study was conducted before Epclusa was ap-proved by the Food and Drug Administration (FDA).

It was noted by the authors that the 8-week regimen of Harvoni was underutilized. Editorial CommentsHow do the direct-acting antiviral drugs work in a ‘real world’ setting as opposed to clinical trials? The Veterans Affairs Healthcare system is a perfect place to test for ‘real world’ results. The results reported in the study above are very similar to the cure rates reported in clinical trials. The direct-acting antiviral drugs are very effective in a clinical trial setting and out in the real world. This is not usually the case. The study also proved that the different drugs (Har-voni and Viekira Pak) had similar cure rates in regards to treating HCV genotype 1. Lastly, it is disappointing that the 8-week treatment regimen of Harvoni was not being utilized to the ben-efit of the patient and as a cost-saving measure for the VA system, the Federal Government and ultimately the taxpayer – you and me!

“The Veterans Affairs Healthcare system is a perfect place to test for ‘real world’ results.”


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Article: Consequences of inaccurate hepatitis C virus genotyping on the costs of pre-scription of direct antiviral agents in an Italian district—E Polilli et al.

Source: ClinicoEconomics and Outcomes Research 2016:8 467–473

Study Aims and ResultsThe authors conducted a study to analyze commercial hepatitis C genotype/subtype assays to understand the cost-effectiveness of potential errors in genotype/subtype assays. The study was conducted between March and September 2015.

It is estimated that approximately 10% of the current assays incorrectly classify genotype/subtype.

In the present study, 134 consecutive patients who had previously been genotyped were retested using HCV se-quence analysis to confirm a prior commercial test before beginning HCV treatment.

It was found that twenty-one (15.7%) HCV patients had been incorrectly genotyped. This error in genotype/sub-type was estimated to reduce the treatment effectiveness by 15% to 40%.

There were 8 cases of genotype 1b that when retested were genotype 1a. This meant that the wrong treatment and/or treatment duration was given.

Lastly, there were 5 patients with HCV genotype 1 with an indeterminate subtype that could have, again, lead to the wrong treatment or treatment duration.

Four patients had mixed genotypes which is important to know because a pan-genotypic drug may be needed to treat those patients.

Editorial CommentsIt is alarming that such a large number of incorrect genotypes/subtypes are being mis-classified by cur-rent assays. Can you imagine going through treatment multiple times and failing and finding out that the assay was wrong? You would think that for such an important diagnostic test the Food and Drug Administration (FDA) would require a higher rate of accuracy.

It’s time to re-test people for genotype/subtype with the most sensitive test BEFORE therapy to make sure the correct medication is prescribed. The added cost of the assay is more than enough justification considering the cost of HCV medications and the welfare of a patient.

“It is estimated that approximately 10% of the current assays incorrectly classify genotype/subtype.”

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Recently I posted a message of praise about an article discussing someone’s story of living with

hepatitis C. I posted it to their Facebook page. Although they are now cured, it never occurred to me that this person might not want the entire Facebook community to know that they had hep C.

I’ve been an advocate in the hep C community for nearly 20 years, and I am shocked by my insensitiv-ity. Fortunately, this person had set their Facebook privacy settings to require approval for all external postings. In short, although I acted thoughtlessly, no harm was done. But, the foul was committed, and my penance is to devote this month’s Healthwise to a discussion on privacy.

Why is there a need for privacy about hepatitis C? Because of stigma. Hep C is stigmatized for a variety of reasons:

• Hep C is potentially infectious. Although it isn’t transmitted as easily as some think, humans can

be quite fearful about infectious diseases. People may react strongly out of their fear of “getting” hep C; so much so, that they may act irrationally. Fear and ignorance have cost patients their jobs, friend-ships and relationships. Some people with hep C have been shunned by their communities.

• Another aspect of the stigma relates to hep C’s association with injection drug use. People and societies often lack compassion and understand-ing about injection drug use. Former injection drug users may feel haunted by their past and want to avoid this label. Active injection drug users who can’t avoid the label, carry the burden of having two stigmatized diseases, addiction and hepatitis C.

• Stigma may also affect those who have never used injection drugs. Misinformed people sometimes as-sume that all people with hep C have used injection drugs despite the many ways hepatitis C may be acquired. Those without a history of drug use do not


How I Nearly Outed Someone’s Hepatitis C Status: A Cautionary Tale

—By Lucinda K. Porter, RN

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want to be labeled as injection drug users. Despite the fact that we need to stop marginalizing drug users, it is understandable when a nondrug user might not want this extra layer of stigma.

Stigma may cause us to look for others like ourselves. The impersonal nature of the internet can feel like a safe place to find others with hep C, a place to ex-change information about how to live with this disease. However, the internet is not a private place. In fact, it is the ultimate public place. Not only do we have to worry about the inadvertent postings by careless people like me, now we have to worry about WikiLeaks.

In August, WikiLeaks published medical informa-tion belonging to private citizens, including peoples’ hepatitis C status. Wiki revealed information about HIV, sexually-transmitted diseases, mental health, victims of rape, and much more. Private identity information, such as addresses was included in these leaks.

Not only is nothing private on the internet, it is forever. Information cannot be erased from the web. So, if you don’t want people to know about your having hepatitis C, don’t tell anyone. However, if WikiLeaks can hack into your medical record, then there isn’t much you can do to protect yourself.

The only way through this that I can see, is that we need to combat stigma. I am not sure how to do this, but I think it starts with unity. Collectively, we must stand together. We can hold each other up, and defend each other as we confront ignorance.

As for my nearly outing someone, I hope I learned my lesson. The decision to go public is a personal one. Although I have never regretted living publically with hepatitis C, it was not without consequences. Fortu-nately, I was not alone, and when I felt the sting of stigma, you were quick to help me mend.

In botany, the word stigma refers to the part of a plant where bees deposit pollen. The stigma bears the fragrant sweet solution that attracts bees. It is a place of fertilization. For those with hepatitis C, it may be the place where shame blossoms into hope. It is time to bring hepatitis C out of the closet and into the sunshine. But only if you are ready. The decision is entirely yours. And if you step into the public arena, I stand ready to walk with you.

Lucinda K. Porter, RN, is a long-time contributor to the HCV Advocate and author of “Free from Hepatitis C” and “Hepatitis C One Step at a Time.” She blogs at

www.LucindaPorterRN.com and HepMag.com

— CONTINUED FROM PAGE 5How I Nearly Outed Someone’s Hepatitis C Status: A Cautionary Tale

Not only is nothing private on the internet, it is forever. Information cannot be erased from the web. So, if you don’t want people to know about your having hepatitis C, don’t tell anyone.

Resources: Hepatitis C Support Project’s A Guide to Stigma and Hepatitis Chttp://hcvadvocate.org/hepatitis/factsheets_pdf/Stigma_Guide.pdfHepatitis C Support Project’s A Guide to HCV Disclosurehttp://hcvadvocate.org/hepatitis/factsheets_pdf/Disclosure.pdf

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Jail and prison officials often say the high cost of HCV management and treatment forces them to create guidelines so those with the greatest

degree disease progression get care first. Such actions lead to rationing which results in people being unaware they have HCV, or discovering they can’t get health care when they ask for it. Rationing occurs throughout the U.S but is likely to be worse in rural counties where there is less moneyfor inmate health care.

To provide a context in discussing HCV management and care, we need to quickly look at the differences between jails and prisons.

Jails temporarily house people under suspicion of committing a crime. People will stay in jail long enough to be sentenced and then they will either go to a prison or home. Transitioning so quickly in and out of jail makes providing health care more challenging. The money for jails to run and provide care to inmates comes from local cities and counties. Management and treatment can become a strain on small rural communities forcing them to make difficult choices on how to stretch what little they have.

Prisons house people with sentences that range from a few years to life. State and federal prisons hold more inmates and have more robust budgets than jails. They also house a larger number of inmates who are HCV+. Prisons can have greater success at HCV management and care than jails because of an inmate’s length of stay.

HCV Screening and Rationing of Treatment

The CDC and U.S. Preventative Task Force (USPSTF) recommend screening for all people with a history of injection drug use and those who were born between 1945 and 1965.1,2,3 Many of people who go into prison or jail are likely to be in one of those two recommended categories. Although high cost is frequently brought up in the discussion of HCV treatment, we know that treating more inmates with HCV will actually prevent transmission in


No Man is an Island: Part 2, Hepatitis C in Rural Southern Indiana

—By Matthew Zielske

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the general population.4,5 Many states do in fact provide some level of HCV services to inmates, although there are only three that provide universal screening.6

Many people are aware of the high baseline cost of the new 12-week regimens. Each state does possess the ability to negotiate prices and come to a bulk price agreement. According to a recent Wall Street Journal article Indiana pays $80,000 per treatment placing it the third most expensive state per inmate for Har-voni. Indiana does provide routine HCV screening and education in state prisons. This is not the case in jails where currently there isn't a blanket policy to offer opt out HCV screening.

Some jails are resistant to carrying out HCV screening because many people won’t be there long enough to complete treatment. Cost related issues such as these have led some jails to privatize their medical services, or reduce different parts of current HCV screening services. In Indiana, all but two of the jails I work in have had their medical services privatized.

— CONTINUED FROM PAGE 7No Man is an Island: Part 2, Hepatitis C in Rural Southern Indiana

Although this may improve care overall by removing the financial burden off of cities and counties, specifi-cally treating HIV/HCV is still the responsibility of the county the jail resides in. This “hot potato” approach to infectious disease management does almost nothing to address the growing epidemic. These services be-ing expensive does not justify limiting access to HCV screening and treatment. Regardless of cost inmates need to be given information on and unrestricted ac-cess to HCV care.

Understanding the challenges faced in successfully providing HCV management and care, the Federal Bureau of Prisons (BOP) released Evaluation and Man-agement of Chronic Hepatitis C Infection, as guidance to jails and prisons. The recommendations give infor-mation on incorporating HCV screening, evaluation, education and treatment among inmates. The BOP recommends HCV screening for all sentenced inmates, all inmates with certain clinical conditions, and any inmate who asks for a screening.7

Going ForwardImproving the overall health of HCV + people will be most successful when working together to find inno-vative ways of improving management and treatment. We can create robust training programs that give the necessary tools to medical staff and correctional employees to provide HCV care. We can create peer education groups inside of jails and prisons where inmates can learn and educate each other fostering an environment where both health and empowerment improves together. We can focus on creating exit proto-cols between jails and local communities where people can access services on release which will reduce the likelihood of someone falling out of care entirely.


“Each state does possess the ability

to negotiate prices and come to a

bulk price agreement. According to

a recent Wall Street Journal article

Indiana pays $80,000 per treatment

placing it the third most expensive

state per inmate for Harvoni.”

UNDER THE UMBRELLAUNDER THE UMBRELLAUNDER THE UMBRELLA

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All of those things will help the overall health of inmates living with HCV, but the biggest achievement to HCV management and care while reducing long term eco-nomic cost, is to either increase funding for jails and prisons or begin applying pressure on them to carry out price negotiations on their own.

We must begin to create a framework for HCV services that is as robust and embedded as cur-

rent HIV services. Many of the individuals currently contracting HCV are people who use substances and inject drugs. This makes accessing them in care whenever possible even more important to the improvement of overall health. If we do none of these things faster than we currently are, we'll wake up in 20 years with economic costs and strains on the medical system that will dwarf what we are currently experiencing.

References

1 Testing Recommendations for Hepatitis C Virus Infection. (2015). Retrieved September 19, 2016, from http://www.cdc.gov/hepatitis/HCV/GuidelinesC.htm

2 Final Update Summary: Hepatitis C: Screening. U.S. Preventive Services Task Force. September 2016.https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/hepatitis-c-screening

3 Chhatwal, J. (2016, October). HEPATITIS C TREATMENT IN UNITED STATES PRISONS PREVENTS TRANSMISSION IN SOCIETY. In 38th Annual North American Meeting of the Society for Medical Decision Making.

4 NCJ 249781, Karishma A. Chari; Alan E. Simon; Carol J. Defrances; Laura Maruschak. July 2016, BJS, (23 pages).

5 Evaluating and Management of Chronic HCV Infection. Federal Bureau of Prisons. April, 2016.

6 AASLD/IDSA/IAS-USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org/. Updated February 24, 2016. Accessed March 2016.

7 Kamarulzaman, A., Reid, S. E., Schwitters, A., Wiessing, L., El-Bassel, N., Dolan, K., . . . Altice, F. L. (2016). Prevention of transmission of HIV, hepatitis B virus, hepatitis C virus, and tuberculosis in prisoners. The Lancet, 388(10049), 1115-1126. doi:10.1016/s0140-6736(16)30769-3

Matthew Zielske currently works as a HIV/HCV special populations prevention specialist at an HIV services organization. He utilizes a harm reduction model in his work with the substance use population focusing

pointedly on persons who inject drugs. He is currently conducting research on Health Literacy and hepatitis C for his Master’s Thesis in Communications. www.umbrellaway.org

— CONTINUED FROM PAGE 8No Man is an Island: Part 2, Hepatitis C in Rural Southern Indiana UNDER THE UMBRELLAUNDER THE UMBRELLAUNDER THE UMBRELLA

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HCV Advocate Monthly Pipeline Update

A brief overview of how this pipeline is laid out:

Date: The Pipeline will be updated on a monthly basis and will be included with the HCV Advocate Newsletter.

Genotype (s): This lists the drugs or combination of drugs and the particular gentoype or genotypes that the drug is active against.

Comments: This section will list the study results. Within this section, I will list the genotype(s) being studied and the phase of the study with a brief recap of the study.

You will note that many of the drugs or combinations of drugs are pan-genotypic—that is they work on many or most of the HCV genotypes. Note: There is more detailed information about the drugs in development in our newsletter (http://hcvadvocate.org/publications/newsletter/2016-2/) and our blog (http://hepatitisc.hcvadvocate.org/)

If you are interested in finding out about clinical trials visit HCV Advocate Clinical Trial Reference Guide (http://hcvclinical.hcvadvocate.org/ ) for a list of trials that are currently recruiting patients.

October 2016 Vol. 19, Issue 10

AbbVie Genotype(s): 1, 2, 3, 4, 5, 6 (Pan-genotypic)

COMMENTS:Genotype 1 – Phase 2 Study: Information from the International Liver Congress 2016: AbbVie’s once-daily therapy of ABT-493 (protease inhibitor) and ABT-530 (NS5A inhibitor).

Non-cirrhotic patients Treatment period - 8 weeks: • Genotype 1: 85% were treatment-naive; 15% were pegylated interferon(PEG)/ ribavirin (RBV) experienced,

cure rates—97% (33 of 34 patients)

• Genotype 2: 87% were treatment-naive: 13% were PEG/RBV treatment experienced: cure rate—98% (53 of 54 pts)

• Genotype 3: 100% were treatment-naive: cure rate—97% (28 of 29 pts)

Treatment period 12 weeks: Cirrhotic treatment-naive patients, genotype 3 – cure rate —100% (24 of 24 patients)

Non-cirrhotic treatment-naive patients (85%), PEG/RBV (15%); genotype 4 (22 pts), genotype 5 (1 pt), genotype 6 (11 pts)—cure rate—100% (34 of 34 pts)

Bottom line: cure rates were 97% to 100%. Now in Phase 3 clincial trials

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Gilead – Sofosbuvir, Valpatasvir& Voxilaprevir (GS-9857) Genotype(s) 1,2,3,4,6, (Pan-genotypic)

COMMENTS:

• Phase 2 study results: I am just listing the cure rates for the optimal treatment duration. • Genotype 1 – Phase 1: 8-week treatment group—treatment naïve patients without cirrhosis: cure rate=100%

(36 of 36 patients); treatment naïve with cirrhosis: cure rates = 94% (31 of 33 patients).

12-week treatment group—treatment-experienced patients without cirrhosis: cure rates = 100% (31 of31 patients) and 100% (32 of 32 patients) with cirrhosis.

1 patient (less than 1%) discontinued treatment because of side effects.

• Genotypes 2, 3, 4 and 6: The cure rates for all of the genotypes 2,3,4 and 6 were combined. 8-week

treatment group—treatment-naïve patients with cirrhosis: cure rates = 93% (28 of 30 patients).

12-week treatment group—treatment-experienced patients without cirrhosis: 100% (36 of 36 patients);treatment-experienced patients with cirrhosis: cure rate = 97% (28 of 29 patients). Three patients (1%)discontinued treatment because of side effects.

The most common side effects were headache, diarrhea, fatigue and nausea.

The combination is now in phase 2 and 3 clinical studies.

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RX

DRUG PIPELINE



Janssen (Achillion/Alios) Genotype(s) 1,2,3,4,5,6 (Pan-genotypic)

COMMENTS:• Genotype 1 – Phase 1: In a small study of samatasvir, it was found to be safe and have antiviral properties

against genotype 1, 2, 3 and 4. There is now a phase 2 study of samatasvir plus Olysio (simeprevir) intreatment-naïve patients with genotype 1b or 4.

• Genotype 1 – Phase 2a Study Janssen (Alios Pharma) has initiated a of AL-335, odalasvir, andsimeprevir to treat HCV genotype 1 treatment-naive patients. There will be 60 patients divided intothree treatment arms who are treated for 4, 6 or 8 weeks. The results are listed in the October 2016 HCVAdvocate newsletter.

• Genotype 1 – Phase 2 Study: ACH-3422 and Odalasvir (ACH-3102) and Sovaprevir are in studies withvarious combinations. Recently, Johnson & Johnson Innovation – JJDC, INC (Janssen) made an investmentin Achillion for co-development and distribution.

• Genotype 1 – Phase 2 Study: Odalasvir plus sofosbuvir (used as a proxy drug) to treat genotype 1 patients for

6 weeks achieved 100% (12 of 12 patients) cure rates. A proxy drug is a drug used to stand in for another

drug. Sofosbuvir is a polymerase inhibitor so it is assumed that odalasvir plus a polymerase inhibitor that

is being developed by Achillion will produce similar cure rates.

• Genotypes 1 through 6–Phase 2b Study: Odalasvir, AL-335, and simeprevir in treatment-naive and

treatment-experienced patients with and without cirrhosis. The trial will enroll 400 patients for six or eight

weeks. The study will include four arms with different combinations of drugs. The trial began in June

2016 and will end in July 2017.

http://hcvadvocate.org/news/NewsUpdates_pdf/Advocate_2016/advocate1016.pdf#HCVDrugs

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RX

DRUG PIPELINE


Merck Genotype(s) 1, 2, 3, 4, 5, 6 (Pan-genotypic)

COMMENTS:

• Phase 2- The study was to evaluate the safety and efficacy of an all-oral therapy. There were three differentgroups that included treatment-naïve, non-cirrhotic patients. The patient population included 93 genotype1 patients, 61 genotype 2 patients, and 86 genotype 3 patients. The treatment duration was 8 weeks. Allof the treatment groups received MK-3682 (300 mg or 450 mg) combined with grazoprevir/elbasvir orgrazoprevir /MK-8408.

Twenty-four percent of genotype 1 patients had resistant associated variants (RAVs): 59% had NS3 (protease)RAVs and 21% had NS5B (polymerase) RAVs.

The overall cure rates were 91 to 100% in the genotype 1 groups; 60 to 94% in the genotype 2, and 86 to91% in genotype 3. The drugs were well-tolerated with no treatment discontinuations.

Part B of C-CREST 1 and 2 will evaluate the most effective dose to treat prior treatment failures, cirrhoticpatients and treatment in people with HIV/HCV coinfection.

Bottom line: The most effective dose was associated with cure rates in the 90 to 100%.

Time Since Treatment RG-101 + RG-101 + RG-101 +Completion Harvoni Olysio Daklinza

Week 12 27/27 pts (100%) 26/27 pts (96 3%) 22/24 pts (91 7%)*Week 16 21/21 pts (100%) 19/20 pts (95 0%) 20/22 pts (90 9%)Week 20 14/14 pts (100%) 13/15 pts (86 7%) 13/13 pts (100%)Week 24 10/10 pts (100%) 8/10 pts (80 0%) 8/9 pts (88 9%)

* One patient missed the Week 12 visit. Viral load results for this patient at week 8 and 16 were collected and indicate thatthe patient was a responder at both time points. This trial is on clinical hold due to safety concerns.

Regulus Genotype(s) 1, 2, 3, 4, 6

COMMENTS:

Regulus Therapeutic Inc.

The study included 79 treatment-naive genotype 1 and 4 patients. RG-101 is a GalNAc-conjugated anti-miR targeting miR- 122, a host factor for HCV infection. It is an injectable medication given at Day 1 and Day 29 plus 4 weeks of a once-a-day direct-acting antiviral medication –Harvoni (27 patients), Olysio (27 patients), Daklinza (25 patients). Regulus issued a press release on June 7, 2016 that reported through 24 weeks of follow-up an additional 4 patients relapsed.

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Executive DirectorEditor-in-Chief,

HCSP PublicationsAlan Franciscus

[email protected]

WebmasterJudy Barlow

[email protected]

Contributing AuthorsLucinda K. Porter, RN

Matthew Zielske

DesignLeslie Hoex

Blue Kangaroo [email protected]

Contact information:Hepatitis C Support Project

PO Box 15144Sacramento, CA 95813

The HCV Advocate offers information about various forms of intervention in order to serve our community. By providing information about any form of medication, treatment, therapy or diet we are neither promoting nor recommending use, but simply offering information in the belief that the best decision is an educated one.

Reprint permission is granted and encouraged with credit to the Hepatitis C Support Project.

© 2016 Hepatitis C Support Project

WE HAVE REVIEWED AND UPDATED THE FOLLOWING FACT SHEETS:

Don’t forget you can view

all of the hepatitis C clinical trials

that are recruiting patients by

visiting the HCV Advocate Clinical

Trials Reference Guide

VERSION 5 • September 2016

Alan Franciscus

What Are Antivirals?

If your liver is damaged by

hepatitis B (HBV), your doctor

may treat you with an antivi-

ral medicine to stop HBV from

making more copies of itself

(replicating). Unfortunately, an-

tivirals stop HBV from replicat-

ing for only as long as you are

taking hepatitis B medications.

HBV can also become resis-

tant – that is the virus can mu-

tate and escape from a particu-

lar medication over time. If this

happens your doctor may switch

you to a different antiviral or add

a second one to your treatment.

There is no cure for HBV, but the

drugs can keep you healthy.

If you have never been treated, doctors suggest one of

these two antivirals:

Tenofovir (Viread) blocks an enzyme that HBV needs to

replicate in liver cells. It results in undetectable viral load

(HBV DNA) in 76% of HBeAgpositive patients and 93% of

HBeAg-negative patients. Drug resistance after 8 years of

use is 0%.

Entecavir (Baraclude) is highly effective in clearing HBV

DNA (67% in HBeAg-positive and 90% in HBeAg-negative).

Viral resistance is rare (1.2%) except in those who have

already been treated with lamivudine and have developed

resistance to that drug (60-70% at year 5).

The following three antivirals cause higher rates of

resistance and should be avoided if you are being treated

for the first time:

Telbivudine (Tyzeka) This has a high rate of drug resistance

greater than 25%. It should not be taken with interferon

because it can cause neuropathy – weakness and pain in

the arms and/or legs.

Adefovir (Hepsera) The resistance rate is 29% after 5 years.

Lamivudine (Epivir-HBV) has a very high rate of drug

resistance – 60 to 70% after 5 years of taking it. It is generally

not given as a first treatment choice.

Below are the 5 antivirals approved to treat HBV. They are pills

that are taken daily. All of them appear to be safe and cause few

side effects, but some cause less viral resistance than others.

HEPATITIS BWe have updated the entire series on HBV treatment

VERSION 5 • September 2016 Alan Franciscus

Medication Guide

SOME QUESTIONS TO ASK:• What is the name of the medication? How much, how often, how long and when should you take it? Should it be taken with food? How should it be stored?

• Are there things (alcohol, grapefruit) or other drugs, herbs or vitamins you should avoid while taking the HBV drugs?• What are the side effects? What is the most dangerous side effect? When and how should you report the side effect to your medical providers?• What should you do if you miss a dose?• How long will it take before the medication will start to work?

Sometimes the way to become healthier is by taking medica-tions. If your doctor prescribes a medication there are many things you should know before starting a new drug.

If you cannot afford the medicine, tell your doctor – some doctors have free samples. Some drug companies offer free or low-cost drugs if you qualify. Some medications cost less than others.

REMEMBER…• If you can’t read your doctor’s handwriting on a prescription, your pharmacist might not be able to either. Ask your doctor to tell you what everything says on the prescription and write it down.• When you get your prescription filled at the pharmacy, compare the drug’s label with what you have written in your own handwriting. Both should be the same. If they are different, talk to your pharmacist first. If this doesn’t clear up the problem, call your doctor’s office.


Help with Medicines Some of the medicines totreat hepatitis B (HBV for short) are expensive. Even if you have medical insurance it may be dif-ficult to come up with the mon-ey for the co-payment fee. If you do not have insurance it can be even more difficult. There are some ways for people who can’t afford the hepatitis B drug treatment. The first one is applying to the com-panies that make the drugs to treat HBV. You will have to work closely with your doctor or nurse to apply for these programs.

These programs also have many services and offer support that you can take advantage of while on treatment. If you are having a hard time paying your bills and have no medical insurance, another op-tion would be to try to get into an HBV clinical trial. Clinical trials are regulated very closely now, and the person who coordi-nates the trial is an advocate for the people who enroll in the trial. Many clinical trials will pay for the medications and for some or all of the lab work that is needed.

FOR MORE INFORMATION

Contact these Patient Assistance Programs

Bristol Myers-Squibbhttp://www.bms.com/products/patient-assistance Documents/

baraclude-patient-assistance-program application.pdfCall: 855-898-0267

Gileadhttp://www.viread.com/co-pay-coupon.aspx

Call (877) 627-0415

Partnership for Prescription Assistance 1-888-477-2669 – www.pparx.org

Needy Medswww.needymeds.org

Clinical Trialswww.clinicaltrials.gov

VERSION 5 • September 2016

Alan Franciscus

Taking HBV Medicines

There are two types of

medicines used to treat

chronic or long-term hepati-

tis B (HBV for short) – antiviral

pills that work by blocking the

hepatitis B virus from making

more copies of itself (repli-

cating), and interferon, which

boosts the immune system to

help fight HBV.

Interferon does not cause drug

resistance, but some of the HBV

pills can cause drug resistance

which could mean that the drug

no longer works against HBV.

Your doctor/nurse will instruct

you on how to take the HBV

medicines – how many, how of-

ten and if you need to take them

with food.

It is very important that you follow the doctor’s instructions

carefully because…

• HBV medicines are more likely to work if all of the medicines

are taken

• It will help to prevent HBV from developing drug resistance.

Drug resistance can develop when the full dose of the drug

is not strong enough to kill all of the virus

• If you stop taking the medicines or reduce the amount of

drug taken, this could lead to a ‘flareup’ or worsening of

the damage to the liver

• Make sure to follow the doctor or nurse’s instructions about

whether you should eat food when you take the pills

Drug resistance is when the hepatitis B virus is able

to ‘resist’ and ‘escapes’. In other words the drug

will no longer work to stop the hepatitis B virus from

replicating or making more copies of itself.


Hepatitis B TreatmentNot everyone who is infected with the hepatitis B virus (HBV) always needs treatment. Doc-tors generally recommend treat-ment only if the virus is damag-ing your liver. There are many factors your doctor will consider, such as

your ALT level (elevated ALT lev-els means liver cells are dam-aged), viral load (HBV DNA), and how sick your liver is. There are two types of drugs available to lower amount of the hepatitis B virus in your blood and help reduce liver damage. Antivirals – are medications (in pill form) that make it hard for HBV to reproduce (replicate), but they usually work for only as long as you take them. They are able to lower the amount of HBV in your body and stop liver damage in about 70% to 90% of patients. Some antivirals lose their effectiveness over time because HBV is able to “resist” the medication and keep replicating. This is called drug resistance.Interferon – Pegylated interferon, given as a weekly injection, boosts your immune system to fight infection. This treatment is most effective when ALTs are elevated and your viral load is not very high. It is successful in up to about 42% of the time. Unfortunately, these treatments cannot cure hepatitis B. To-day, doctors often try one drug (either an antiviral or inter-feron) first, and then may try another if you continue to have a high viral load and signs of liver damage. There are many researchers who are trying to find a cure.

REMEMBER…• Not everyone needs to be treated.• Antivirals can lower your viral load while you take them. Talk with your doctor about the one with the lowest risk of viral resistance.

• Most doctors won’t treat you unless your ALT is elevated, or you have been infected for many years, or you have other signs of liver damage.• Work closely with your doctor and discuss the best treatment options that are right for you.

CLICK TO DOWNLOAD

HCV Advocate’s ClinicalTrials Reference Guide for information about HCV clinical trials that are currentlyenrolling patients.

http://hcvclinical.hcvadvocate.org/

CLINICAL TRIALS

The local, state and national election is November 08, 2016.DON’T SIT THIS ONE OUT!

To find out how to register in your state. Go to the official website of the United States Government listed below



https://vote.gov/?1

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www.hcvadvocate.orgHCSPP.O. Box 15144Sacramento, CA95813

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