New Drugs, New Treatments, New Hype

In mid-June of this year while at a baseball game watching my childhood hometown Minnesota Twins defeat my adopted home town team San Francisco Giants, a friend asked if I was excited about the news in the paper that morning about the new cure for Hepatitis C. He said that it cured 80% of all patients in clinical trials and that the treatment might last only 24 weeks instead of the standard 48 week therapy. The news was stunning. Which drug was it? I had been keeping up with the various new drugs in the FDA approval pipeline and had never heard of one with a viral clearance rate of more than 65%. Of course he couldn’t remember the name and none of us had a smart phone with us, so it took until after game and back at home before I could do any research.

This article appeared in the San Francisco Chronicle. It stated that about 80% of HEP C patients “with the most common strain” and relapsers from previous treatment were cured by the new drug. The drug was the protease inhibitor telaprevir, brand named Incivek by its developer Vertex Pharmaceuticals. Imagine the amount of money they must have paid a naming company to develop that brand name; rolls right off the tongue. The results from earlier studies had indicated that telaprevir increased the Sustained Viral Response (SVR) in genotype 1 HEP C, the most common genotype infecting US residents, to 65%. It seemed prudent to search out the source material to sort out all these percentages. A quick search of the web found this press release. In the fourth paragraph of the release it stated that “The sustained virologic response for patients treated with Incivek across all studies, and across all patient groups, was between 20 and 45 percent higher than current standard of care.” This seems to indicate that the low end of the SVR rate was indeed 65% and the high end might be almost 90%. The article and press release also indicated that 60% of treatment naïve patients achieved a rapid viral response (RVR) in 4 weeks and these folks not only would only be in treatment for 24 weeks, but had a 90% chance of achieving an SVR as well. It is not clear what the SVR rate for the folks who don’t achieve a RVR and continue for 48 weeks of treatment has been in the tests. It is also unclear whether there is a difference in SVR rates between genotype 1a and 1b. Folks who had relapsed after previous treatments had a 32% SVR rate when treated with the telaprevir, interferon and Ribavirin cocktail. This is very good news indeed for HEP C patients.

A month earlier, this article appeared in the NY Times announcing the debut of Victrelis the brand name of boceprevir (again where do these brand names come from) another protease inhibitor, this one developed by Merck. This drug, which is taken for either 24 or 48 weeks in combination with interferon and Ribavirin, has an SVR rate for treatment naïve genotype 1 HEP C patients of 65-70%. The SVR rate for patients who relapsed after previous treatment is about 40%. Boceprevir is a bit different in that the patient starts with 4 weeks of standard treatment and then adds the boceprevir for either an additional 24 or 48 weeks depending on the viral response. So we have two competing drugs available whose addition to the standard of care treatment increases the SVR rate by a range of 20 to 40 percent. Good news indeed but what is the rest of the story.

The rest of the story has several chapters from side effects to cost of treatment. Looking at side effects first, both boceprevir (Victrelis) and telaprevir (Incivek) have additional side effects to add to those caused by interferon and Ribavirin and both can somewhat intensify the interferon and Ribavirin side effects as well.

Boceprevir can increase the risk of anemia and neutropenia, cause strange taste sensations and cause intestinal tract issues.
Telaprevir also increases the risk of anemia, causes diarrhea, and most importantly can cause an itchy rash. The rash can be serious enough to require that the patient stop taking the telaprevir.

The new drugs are very much like the established treatment in that those with lower viral loads at the beginning of treatment have a better chance of success than those with high viral loads. Also like the established treatments, anyone who has ever tried a treatment, whether standard or experimental, and failed also has a considerably lower chance of success.

Both drugs are protease inhibitors. This means that they inhibit the action of an enzyme that the virus needs to reproduce. They are similar to the protease inhibitors developed to fight the AIDS virus. This means that they must be taken on a fairly rigid schedule: three pills per day, one every eight hours. If that means waking up to take it, wake up you must. They also need to be taken with food, so you cannot pop a pill and run off. You have to have certain types of food with the dose of the drug. This means that for 12 weeks (telaprevir) or 24-48 weeks (boceprevir) your life will be scheduled around your drug dosing.

Both drugs are vastly expensive as discussed in this article. Boceprevir/Victrelis will cost $1,100 per week making the cost of a full course of the drug either $26,400 (24 weeks) or $52,800 (48 weeks) depending on your viral response. Telaprevir/Incivek has been priced at $49,000 for the 12 week course of treatment. This cost is in addition to the $15,000-$20,000 (24 weeks) or $30,000-$40,000 (48 weeks) for the interferon and Ribavirin with which they must be taken. This also does not count the cost of the Procrit to fight anemia ($500 per week) or the Neupogen to fight neutropenia (also about $500 per week) should you need them. There are also the costs involved with antidepressants, sleep medications, thyroid medications, pain medications and whatever you will be using to deal with the rash and itching in the case of the telaprevir.

It is also not clear how quickly insurance plans will add them to their drug formularies. Kaiser Permanente, my HMO here in California, has added both to its formulary. I do not know which other insurance providers have done the same. Even if they are added, it is not clear what the requirements will be for a patient to be eligible to be prescribed and how easily insurance companies will make them available. From an economic point of view they should make them easy to get as even at these prices the cost of treatment is still much less than the cost of a liver transplant.
For those without insurance, I do not know how anyone but the wealthy could afford the additional cost. The cost of standard of care treatment is by itself so high as to exclude many HEP C sufferers from being treated. There are programs to assist those with low resources to get treatment but even with the drugs deeply discounted the ability to come up with as much as $20,000 for a course of treatment would seem impossible.

Despite all these potential problems, the advent of new drugs to combat HEP C is excellent news. Ramping up the SVR rate to a range of 60% - 80% is a vast improvement over the standard of care treatment rate that topped out at 45%. Psychologically, it is far more encouraging to go into a course of treatment thinking you have a 2-1 shot at beating the virus than to go in thinking you have just under a 50-50 shot. These drugs are also only the leading edge of a wave of new drugs and new therapy approaches that are under research and testing. There are new polymerase inhibitor drugs that have SVR rates similar to telaprevir, but with fewer and less severe side effects. Testing on the holy grail of finding a treatment regimen that does not have to include interferon is also underway with early stage results coming in soon. Within the past year, scientists have discovered a method of growing the HEP C virus in the lab. This means that future early stage testing of drugs can be done directly on the virus instead of with animal models. This should increase the pace of research dramatically. In all it is a good time to have HEP C if you are one of us infected. There are established treatments, there are promising new treatments and there are drugs and treatments in the research and development pipeline that seem to point to future in which HEP C can be attacked and treated with a high expectation that it will be successfully cleared from the human body.

Perhaps we can believe the hype surrounding these new drugs. Despite the problems of determining the actual efficacy of the drug in your own case, the potential difficulties in obtaining and paying for the treatment and persevering through the side effects, they have advanced the cause of combatting Hepatitis C.

The more cures, the fewer pig livers will have to be implanted in humans (sorry, I’ve been reading far too many science fiction novels during treatment).

Sitting In Limbo

After not getting in to the Vertex – Telaprevir study in January of 2009 and being thrust into a primary management role in my employer’s reorganization and construction project in early 2009, I ended up in limbo regarding my plans for dealing with Hep C. I was so exhausted from running the project that I did not have the energy and mental focus to make any informed decisions.

One of the good pieces of fallout from not being in the study was getting to meet the team at the California Pacific Medical Center (CPMC) Hepatology Center. The study coordinators are not only intelligent, empathetic people, but they genuinely felt bad about the circumstances of my not qualifying for the study. They knew that the bad test result had been a result of a lab testing glitch and that I was a good candidate for being in a study. So they kept me informed of the various studies that were in the pipeline at their center. I told them that I would not be able to do anything until the summer as I needed time to recover and get the new systems at work up and running. But as soon as May and June arrived, I began to get phone calls about studies. I turned down one that was an early phase 1 trial of another protease inhibitor as it was a short (4 week) trial to determine whether the drug had any efficacy against the Hep C virus. I did not want to do a short course of treatment. When I committed to a program, I wanted to have it be for a full-term course of treatment designed to wipe out the virus. I also did not want to give up my treatment-naïve status unless it was for a serious, later stage study that was trying to determine whether the test drug was good for a cure, not just good for some effect against the drug.

Treatment-naïve means that you have never taken drugs to combat Hepatitis C. This is the state that most researchers look for in test subjects. They want to test their compounds on people whose Hep C virus has never had the chance to react to any attacking drugs. You are only treatment-naïve once. As soon as you have taken drugs to attack your Hep C, whether it be the standard Interferon and Ribavirin therapy or a drug study involving alternate or additional drugs. So, if you are considering entering a medical research trial, you may want to protect your treatment-naïve status until you see a study you like. Of course, if you are in serious later stage liver disease, you take the treatment that sounds best to deal with the situation you have and the hell with preserving treatment-naïve status for the future.

There are also studies for treatment-experienced patients as well. These studies are often somewhat later phase 2 or 3 studies that are trying to determine if the study drug works were other drugs have not. Let’s face it, if you can develop a drug that not only can cure Hep C in treatment-naïve patients, but also can cure the disease in people have tried other treatments and failed, you are looking at a much bigger slice of the treatment money pie. So drug companies all want to know if their drug works where others have failed. There is no need to despair of being able to access experimental therapies just because you have already tried a drug regime and failed. This is a thought that I hold clearly in my head when I think about the possibility of relapsing after the trial ends. I can still go for other options, assuming I want to go through this experience again.

So I was indeed drifting a bit, trying to see if an interesting study came up and indeed thinking about the whole necessity of entering treatment Right Now. As the immortal Jimmy Cliff would have it, I was indeed sitting here in limbo, waiting for the dice to roll.