ANTIVIRAL RESEARCH PROGRAM AVAILABLE AT OCHSNER CLINIC

Antiviral research programs are sponsored by pharmaceutical companies. Research studies do not generally involve costs for the patients, except as this may apply to screening visits to determine eligibility or for the cost in travel to and from the Ochsner Clinic. Sometimes research budgets allow for partial compensation for ground travel. The research programs are conducted on an outpatient basis and patients self-administer the medication. Most studies involve a comparison of the investigational drug's performance and safety to a standard medical treatment, such as interferon. Some research trials incorporate the use of placebos (inert agents with no antiviral effects), but these studies generally allow for treatment with the investigational drug if it is shown to have proven benefit in the patients who are initially treated.

TREATMENT OF CHRONIC HEPATITIS C

Background

Until recently, conventional treatment of chronic hepatitis C has involved the use of six months of interferon therapy given alone in a dose of 3 million units three times weekly. While this regimen was generally well tolerated, only a small minority of patients (10 to 20%) was found to respond in a lasting way. Recently, it has been recommended that interferon be given for one year. This results in a somewhat higher rate of lasting response (20 to 30%), but may be less well tolerated. At the Ochsner Clinic, it is our contention that some of the unpleasant side effects as well as the limited efficacy of interferon is due to the fact that this agent has been given intermittently (i.e., three times weekly) and in too low a dose. The following research programs available at Ochsner will hopefully lead to a more effective way of treating chronic hepatitis C with equal if not better tolerability than current regimens:

1. Combination therapy with interferon and ribavirin. Ribavirin is a broad spectrum antiviral nucleoside analogue that can be taken orally. It has little activity against hepatitis C when used alone, but a number of medical reports indicate that there is a higher lasting response rate when this agent is used in combination with interferon. Currently, we are studying the use of interferon and ribavirin for the following three groups of patients:

Treatment new or naive

Relapsers after previous interferon treatment

Interferon nonresponders

Important facts to keep in mind about the combination protocols:

(1) All patients in this study are treated with the combination therapy; there is no placebo group.

(2) Patients must have insurance which enables them to cover the cost of the interferon therapy (ribavirin is provided free) and any additional costs for their care at the Clinic. This is necessary because the studies are not financially supported by the pharmaceutical industry.

(3) Finally, the studies take advantages of several innovations in interferon therapy:

First, induction therapy is used. This means that interferon is given daily for the first month; there are data which indicate that this may lead to a higher rate of initial virologic response.

Second, therapy is continued for one year, which as mentioned above is more effective than six months of treatment.

Third, therapy is given on alternate days for 11 consecutive months rather than three times weekly to deliver more drug.

Finally, therapy is combined with ribavirin to increase the chance of a lasting response.

In these studies, the dose of interferon is based on the age of the patient. Patients less than 50 years of age, receive 5 million units for one month, followed by 5 million units on alternate days for 11 months. Patients over the age of 50 receive 3 million units. We feel that the regimens described above provide the greatest chance of lasting biochemical and virologic response.

2. Sustained release (PEG) interferon. Polyethylene glycol is an inert carrier in a number of medications. Four interferon molecules are bound to this material in a sustained release formulation of interferon (PEG interferon) which is designed to provide more steady blood levels. The medication needs to be given once weekly instead of three times weekly.

More sustained blood levels of interferon could be a more effective way of giving interferon, since it could result in a lower rate of interferon resistant viral variants. Equally important, sustained release interferon appears to be better tolerated, avoiding the "highs" and "lows" of interferon therapy given three times weekly. A study is underway at Ochsner Clinic comparing one year of PEG IFN given once weekly in one of three different doses to 12 months of conventional interferon given three times weekly (randomization is 1:1:1:1).

There are no medical costs associated with this research protocol since both the PEG interferon and study visits are supported by the manufacturer of the drug (Schering Plough).

FROM THE OKANAGAN

August 23^rd to 25^th, I attended the HCV Global Foundation conference in Oakland, California. It was appropriately titled "The Silent Epidemic of Hepatitis C."

I was invited by HCV Global to attend the conference and to make presentations on two panels. This was very difficult, as they had at least 6 other panels happening at the same time, and I wanted to take them all in, not attend the ones I knew the most about!

I was asked to speak on the topics of Hepatitis C and Youth, as well as the FDA Lookback. I felt privileged to be presenting with Thelma King Thiel (HFI-Hepatitis Foundation International), Dr. Norwood Hill (Texas Blood Banks), Dr. Nora Hirshler and Dr. Thomas Jackson. It was very interesting to listen to the different perspectives on what the FDA lookback study should look like when it finally gets implemented. They were very interested to hear what had been done in Canada and about any flaws in the process we had found!

My being in California on these panels brought forth opportunities I never dreamed of nor imagined. I was invited to join the Pacific HCV Support Group Coalition. This is an organisation of support group leaders from Washington, Oregon, California and B.C. who will meet regularly (via email) to discuss HCV walks, ribbons, information, media, speakers, scholarships, newsletters, organ donation awareness, clinical trials, etc. It sounds like a very committed group, with many goals to work toward!

I met some awesome individuals and left California with my wheels spinning. Roulette Smith gave an absolutely brilliant talk about research and the future of HCV. Jean Shinoda Bolen, MD, was inspiring as she described her journey to the mind, body, spirit connection. Chris Sandoval and Matthew Dolan offered other approaches to dealing with the same issues. From Alternative Approaches to Harm Reduction, Social Security & Disability Issues to Substance Abuse there really was something in it for everyone. I managed to take in a few of the panels and found them very informative and entertaining. Ron Duffy and all his helpers at HCV Global need to be applauded for a very successful conference.

Upon my return home I was called and asked to join, as an advisory board member, the team at Hepatitis C Hope Incorporated. It is an honour to have been asked and accepted as a member. This is the group based in Texas that has launched the $50 billion class action suit, on behalf of those transfused with hepatitis C. I am very excited about travelling to Texas and working alongside C. W. Henderson, Dr. C. Everett Koop and Andi Thomas. The windows of opportunity are opening in my direction.

We will be travelling to Ottawa for the opening of Parliament the week of the 21^st of September. I am thrilled to be joining many others as we gather to let the Prime Minister know we have voices and are prepared to use them in seeking fair compensation for all!

Until next time....take good care of yourselves,

Ms. Joan King-Diemecke

Treasurer, Hepatitis C Society of Canada, Victoria Chapter

1611 Quadra Street

Victoria, BC V8W 2L5

Dear Ms. King-Diemecke

Thank you very much for your letter of September 1st. We enjoyed meeting you and your colleagues from the Victoria Chapter of the Hepatitis C Society of Canada, You were particularly interested in how the Canadian HIV Trials Network could assist with the development of an enhanced hepatitis clinical trial capacity in Canada. We were happy for the opportunity to learn more from you about the challenges of living with hepatitis C.

Like you, many others have noted the parallels between HIV and the hepatitis C virus. Both are chronic, debilitating diseases and both will continue to take a dramatic toll on the health of Canadians for decades to come. For neither disease is there anything even approaching definitive therapy, and the need for better treatments and a cure is urgent and compelling. Sadly, both these epidemics are converging in our most vulnerable populations, and the number of people who are co-infected is rising. As a result of these clear parallels, we are often asked whether the CTN model shouldn't also be applied to HCV.

We believe hepatitis C treatment remains at the stage HIV was 10 years ago with a few relatively ineffective drugs to offer patients. The need for clinical research is clear. But, our ability to attract experimental therapies at the earliest possible time for affected Canadians will depend on whether our country has a ready and able research infrastructure, and on Canada's ability to attract state-of-the-art clinical trials.

I think there are a couple of options as to how we can help you in your quest to establish an HCV trials network. One means is to expand the mandate of the CTN to include HCV. This has been suggested by a number of people in the recent past. But as I explained, this would require some important steps. We would need to consult with the HCV patient community and with those physicians and health care workers already treating people with HCV and perhaps doing research in the field to ensure that they are all an integral part of this important response. Equally, we would need to discuss this with our own advisory boards and the HIV community. There may be concerns that time and energy spent on HCV might detract from HIV research. On the other hand, it has been pointed out that efforts against HIV and HCV can be synergistic rather than competitive, and that the whole could be greater than the sum of its parts.

The second way we could help is to transfer everything we've learned from our eight years in operation to a new "trials network for HCV."

Many observers have tried to impress on us the efficiency of expanding the CTN's mandate rather than setting up a whole new infrastructure. The CTN already has a network of investigators comprising Canada's leading infectious disease specialists, many of whom are involved with the treatment of Hepatitis C, or who work closely with colleagues who do. The CTN is also experienced in working cooperatively with advocates and activists. After successfully including people living with HIV on all our committees, we've learned research can be inclusive and scientifically excellent at the same time, a reality that is sometimes lost on researchers in other fields. Because the CTN already has a data centre in place, the need for a new infrastructure to collect and process data from clinical trials need not be duplicated. This infrastructure includes computers and computer networks, academic faculty, database programmers, data analysts, biostatisticians, and data managers. Finally, we have a standing National Ethics Review Committee and a Safety and Efficacy Committee already in service. All of this together means the saving of Canadian tax dollars, and most importantly, the saving of time for people living with hepatitis C who desperately need access to new and better treatments for the disease.

I know it is difficult for you and your colleagues at the Hepatitis C Society to focus on research while the compensation issue is still outstanding. We agree with you that both issues should be pursued simultaneously. Also, we agree with your view that any funds put towards HCV research by the federal government should in no way replace or jeopardise compensation dollars.

Whether Canada chooses to build on the CTN infrastructure to support hepatitis C trials or to create a new national trials network, we will assist you in any way we can. Please feel free to contact us about this for further discussion. As you suggested, we would be happy to meet with your colleagues at the national level at their earliest convenience.

Sincerely,

About the time I was finishing the 1st edition of the Handbook, I was becoming increasingly aware of the shortcomings of interferon based therapies for hepatitis C, as well as their lack of suitability and efficacy for many patients. Market conditions and the structure of the pharmaceutical industry meant that alternative therapies, such as amantadine, were being edged out, or only offered with interferon. Thus the available options were settling down to interferon or nothing for most people. When I actually analysed the figures for contraindicators (both lifestyle and clinical) and incorporated the non or partial response rates, coupled with the outright patient refusal rate, it was readily apparent that the generally available solutions were not well matched to the actual needs of most patients. I was also beginning to meet apparently "cured" interferon patients, who reported that they were more debilitated after therapy than before it.

It was also crystal clear that just about all of the patients attending the Gateway clinic were saying that they were getting better, particularly in terms of day-to-day functionality, but also reporting improved clinical results. It was also noticeable that John Tindall's patients who decided to "do" interferon were finding the side effects far more tolerable than those who did not take concurrent herbal treatment; this was obvious from the greatly diminished "drop out" rates among his patients taking interferon based therapy.

I had been using Chinese herbs prescribed by John Tindall of the Gateway clinic, (an internationally respected National Health Service resource located in London), for a while, and had experienced dramatically improved levels of energy, and had noticed that my LFTs had become persistently normal. This experience was normal among his patients. Then I received the results of a recent PCR test, showing that my viral load had declined from 5 million units (2 tests before starting herbs, 1 in the early stages) to 40,000 units. In other words, my viral load was now less than 1% of the level that it had been prior to the commencement of Tindall's Chinese herb based therapy.

Although I knew that feeling better and having healthy LFTs would be of interest to many patients as therapeutic outcomes, it was the decline in the viral load that really triggered me into some action. I discovered a few other examples of diminished or disappeared virus (though usually only interferon patients have PCR measured in London, so results are hard to come by). Generally, it was obvious that this was, in many respects, a more attractive, better qualified and deeply rooted option to currently available drug therapy.

I had some doubts about getting involved in the production of medicines for HCV, largely because I was a respected writer on the subject, and I knew it might raise questions of impartiality. However I also thought that it would be ethically questionable not to do something that might benefit other patients, particularly when I knew that the balance of evidence strongly suggested that this was a great source of potentially beneficial treatments and that I was very well placed to take this initiative.

I therefore approached John and asked him if he thought it would be possible to produce some broad range herbal formulations for general use, with a view to letting a wider percentage of the patient population benefit from his expertise.

He decided that he could design some broad range formulations which could deliver a good probability of benefits in particular subgroups of patients. Above all it was possible to design formulations which would be safe, so that the worst outcome would be that they would not work. (This remains the qualification to these products). We approached East West Herbs and were able to negotiate the production of heavily quality controlled tableted versions of our first 2 formulations.

John, I, and around 15 other patients, some of whom are extremely able and well-qualified, are now involved in setting up a national charity which will aim to create a centre of excellence for the multidisciplinary treatment of HCV, and will also serve as a centre for research. This will be called The Yuan Centre. (Or clinic?) (Yuan means "source"). It is hoped that the herbs will become sources of income for the Yuan Centre thus benefiting everyone, and removing the hassle from John and me.

But the hard part of this treatment is remaining PCR negative because the odds do not necessarily favour me. I did not respond initially and my PCR was very high. Both of these parameters have been shown to negatively affect a sustained response.

I have heard some people refer to the combination as a possible cure. As hopeful as I am, a word of caution is necessary. We need to remember several things. First of all, the criteria for measuring a cure has been remaining PCR negative for six months. This is far too short time. We all know how successful this virus is at hiding. If someone were to remain undetectable for five years, I might consider using the term cure.

The second item of concern is the fact that the PCR is still performed using blood. We all know that the virus resides in the liver. But performing a PCR on liver tissue is beyond our current resources. This test is very specialised and requires expensive equipment that isn't readily available. But a person could be PCR negative using blood and PCR positive using liver tissue. This is very frustrating for all of us.

So we must use great caution when we use the word cure. It can have the effect of placating the public and removing HCV as a cause for concern. We must have research dollars from the government going into hepatitis C. We must have funding for clinical trials for HCV. Every single person that has HCV should be receiving some kind of treatment, or be in a clinical trial. What happens to the people that fail to respond to combination therapy? At this point there is nowhere for them to go. We sit and wait. Waiting for another treatment option. Waiting for the virus to continue its damage. Pushing the envelope of time closer and closer to the edge. This is not an acceptable alternative.

I implore those of you that are not symptomatic to get involved. We need to lobby the government for funds. We must have a clinical registry set up for HCV trials. We dare to hope for a cure, but only YOU can make this objective our reality. Do not become passive victims. Get involved. Collectively we CAN make a difference.

Elections for the steering committee of the Victoria Chapter of HeCSC will be held at the November meetings. Nominations may be made in person at the October and November meetings.

Camp Church and Associates

Sharon Matthews / Kim Graham

4th Floor, Randall Building

Vancouver, BC V6B 1Z5

1-888-236-7797

Grant Kovacs Norell

Bruce Lemer

Grosvenor Building

930-1040 West Georgia Street

Vancouver, BC, V6E 4H1

Phone: (604) 609-6699 Fax: (604) 609-6688

Before August 1, 1986

Klein Lyons

David A Klein

805 West Broadway, Suite 500

Vancouver, BC V5Z 1K1

(604) 874-7171 or 1-(800) 468-4466

(604) 874-7180 (FAX)

also:

Dempster, Dermody, Riley and Buntain

William Dermody

4 Hughson Street South, 2nd Floor

Hamilton, Ontario L8N 3Z1

(905) 572- 6688

The toll free number to get you in touch with the Hepatitis C Counsel is 1-(800)-229-LEAD (5323).

Pre 1986/post 1990

Mr. David Harvey

Goodman & Carr

200 King Street West

Suite 2300

Toronto, Ontario, M5H 3W5

Phone: (416) 595-2300

Fax: (416) 595-0527

TRACEBACK PROCEDURES:

The Canadian Red Cross Society

4750 Oak Street

Vancouver, BC, V6H 2N9

1-(888) 332-5663 (local 207)

This information is for anyone who has received blood transfusions in Canada, if they wish to find out if their donors were Hep C positive.

If you would like more information about class action/compensation, you can contact:

Tricia Plunkett Tel. (250) 479-5369

E-mail: plunket@islandnet.com