Protons, Electrons, and Hepatitis C

Protons, Electrons, and Hepatitis C

Well, technically that title should be PROTON, ELECTRON, and Hepatitis C, the first two words being the names of two recent studies of PSI-7977, a potential new drug for treating hepatitis C virus (HCV).

The Latest Findings

There’s a lot to talk about with PSI-7977—mainly in light of study resultspresented a few days ago at the 62nd Annual Meeting of the Association for the Study of Liver Diseases (AASLD) in San Francisco. So let’s get the elephant in the room out of the way before we go any further: I do not know what POSITRON and ELECTRON stand for. Nor do I know what FISSION, PROTON, and ATOMIC stand for—but more on that later. All I can tell you is that at some point in the history of drug development, pharmaceutical companies and/or clinical trial cooperative groups decided that acronyms were necessary or advantageous for some reason, paving the way for many a BLT, BOLERO and COMFORT for years to come.

PSI-7977 is kind of exciting. In the PROTON study, this drug, a nucleotide analog, was combined with the then-standard of care, pegylated interferon plus ribavirin. (Since PROTON was done, telaprevir and boceprevir were approved, changing the standard of care.) In PROTON, 96% of patients had a sustained virologic response (SVR), which is the measure of cure for HCV. Now, to balance this, is a wonderful moment of parsing the data: 96% is impressive, no doubt, but it has to be mentioned that the total number of patients in that study was 25, with 24 patients being actually evaluable. It was an early-phase study, so that small number of patients is not unusual, but most reports about the latest PSI-7977 results are highlighting that initial 96%, and it’s hard to find the actual N of the study. Here is a PDF of the full report of the PROTON study.

After PROTON delivered its encouraging results, Pharmasset, the maker of PSI-7977, launched ELECTRON, a phase II study in which a number of patients were given the experimental drug plus ribavirin. And that is the key: 10 of the enrollees received NO pegylated interferon. And guess what: the combination worked. All 10 of those HCV patients had an SVR.

Now, a couple of things to explain. First, these were patients with genotype 2 or 3 HCV. The reason why these genotypes were selected is because they tend to be highly responsive to interferon. Wait – so, why were those the people who were not given interferon? Well, the logic was that if PSI-7977 plus ribavirin didn’t work, those patients could be more easily rescued with a course of pegylated interferon + ribavirin than HCV patients with, say, genotype 1, the most difficult to treat variety of the disease. As it turned out, that rescue therapy wasn’t needed, but still, the logic is interesting when it comes to understanding drug trials.

more:  Protons, Electrons, and Hepatitis C

Hepatitis C:"Joe, it's the end of you. Fat drives the progression of the disease."

Hello folks, I have to admit, this is a pretty down day for me. The gravity of having a life threatening illness sometimes gets the best of me. I am not looking for sympathy, but it is nice to know that I am not the only one. I want to write today about a fact that I learned all too late for me, but it may be just in time for someone out there who happens to read this in search for answers to the Hepatitis C dilemma. I was over weight when I was re-diagnosed with Hepatitis C, genotype 3, in 2000. Although my GI doctor frowned about my obesity, (ironically, he is now obese!), I do not remember him saying anything more than cautioning about the usual consequences and said, "... you are in stage 1with minimal scarring to the liver. You'll probably die of something else altogether". In 2006, he did a liver biopsy and still stage 1. In 2009 the bomb was dropped, stage 2-3 and still no instructions about my weight. (I'm getting to the point, thanks for your patience). In January of this year 2011, I was referred to an end stage hepatoligist, (a liver specialist), in my city once a month. But I was drawn to this other doctor in Oakland, about 40 miles away. He said,”Joe, it's the end of you. Fat drives the progression of the disease and you are now stage 4 of 4. You have no doubt a fatty liver and that is why your 2nd treatment attempt failed.

Stunned, I left the office and drove home in a daze. How could this be? Why didn't anyone tell me? I will lose this weight! I knocked off 50 of the 60 lbs. I needed to lose in 6 months with diet change and exercise. Weight Watchers is a good method because you can eat whatever you want and still hold yourself accountable.

When I returned to the doctor in Oakland, he was astonished. "You look so much younger! This is huge!"

So the bottom line is now that I have lost the weight and am in the best shape ever, I have a good chance of treatment being effective, but I still have only around a 50%-60% cure rate because of the prior attempts and no new drugs that work on genotype 3 as their are for other genotypes of Hepatitis C.

I have a resting pulse rate of a runner, but it may be all but academic. My hope is that I can save someone else like I could have been saved by knowing this information. Yes, it may have progressed anyway, but I know in my heart of hearts, it was the fat that made me have to bail in the 3rd week of my 2nd treatment attempt. There is a passage in the bible that says, "Without knowledge, my people perish". I'll get the chapter and verse and add it in later but I must post this now!