This morning I read with great satisfaction that Gilead Sciences is proceeding with yet even more studies on Ledipasvir combined with Sovaldi (Sofosbuvir), with and without Ribavirin. What is noticeably absent is the mention of the dreaded bug juice- Interferon.
For over a decade we have been subjected to more and more new, improved products that swore to be able to kill the dragon. Each one ratcheted up a few percentage points in success but none even came close to the magic 80% and beyond. In fact, if you go back to the early Interferon days, we were shooting up what would be considered a week’s dose in one shot. People who did this are either no longer with us or are so compromised as to be mushrooms in the basement. Actually, if you were to even contemplate that size a dose today, doctors would tell you it was a death wish. Where the hell were they when our good friend Mark of recent VA win fame was told it was okay to shoot up two doses a week instead of one (of the huge doses) as it would probably hasten his SVR. This brain fart came from-who else- VA doctors.
The advent of Ribavirin was heralded as the panacea to knock this bug on its ass. If you consider an increase in SVR (Sustained Virologic Response aka a cure) from 33% to 37% a watershed event, then you were a born optimist. When I took my first shot April 12th, 2007, I was told I had a 66% chance of killing it (genotype 3A) within 26 weeks. Unfortunately, they neglected to read their own baseline testing and spot the autoimmune issues staring them in the face. Much like Roseanna Rosannadanna, I almost died.
The next big invention (that is actually still being promoted) was the triple drug cocktail involving Telepravir/Boceprivir combined with our other two old friends Interferon and Ribavirin. The percentage of SVRs continues to go up but they in no way shape or form got to the magic land above 80-85%. How about 65% if you could stand the side effects long enough to attain remission? Recently, Vertex pharmaceuticals, the makers of Teleprevir, sold out their product for $152 million- in effect conceding the future of protease inhibitors is going down the tubes. Smart choice. I suspect it won’t be long before Merck-Victrelis (Schering-Plough etc.)(Boceprevir) and the others follow suit assuming they can find someone interested in buying it.
I think the biggest 800 lb. gorilla infestation that resided on the living room sofa all these decades was the continued insistence that Interferon caused no more than”flu-like symptoms”. More recently, the Vertex/Victrelis cheerleaders were saying it causes “diarrhea”. Pardonnez moi. I beg to differ. Everyone, and I do mean everyone I’ve talked to, that has used Interferon has a far different take on it. Since when did downstream issues after the flu entail going blind, thyroid cancer, endless depression, anemia, malaise and making your teeth rot out of your head? If you were watching TV and the announcer started running off a litany of things (as they currently do) that might be considered adverse effects, like having a stiffy for over 4 hours because you really wanted to be all you could be in bed, you’d nod sagely and say ” Ne problemo.-not me”. But if that same announcer began with “If symptoms continue or you notice your teeth falling out, discontinue use and call your doctor. Has caused thyroid cancer in most lab rats. May cause blindness and major clinical depression to include thoughts of harming oneself. As with all drugs, results may vary.”
I have read extensively about Interferon since its discovery in 1959. The wonder drug, touted as being nothing more than a ” medical leg up” and “something your body manufactures naturally”, was initially produced and proclaimed a cure for cancer. Funny how that story changed in a hurry. I notice cancer is not on the verge of disappering any time soon. Again, in the late eighties it was trotted out as the new panacea for AIDS. That revelation quietly died (along with a lot of AIDS sufferers) and we didn’t see it appear again until the mid-90s when-guess who- arrived. Each succeeding “medical breakthrough” on this drug was accompanied by the “Let’s just give it a chance to work. We know it works. Some just need to do it several times to kill the bugs.” This idiotic mindset that the drug was (and is) safe has festered now for over forty years. The trail of destruction in its wake is amply documented but they still drag it out as some kind of wunderdrug with acute, non-life threatening consequences.
Gilead has been combining it in a new triple drug therapy with Sovaldi and Ribivirin as the go-to combo to kill recalcitrant Genotype 1A and 1B. When do you suppose they’ll get around to doing a retrospective study of the folks who were horribly maimed by the “flu-like symptoms” but never cured? Fortunately for us, the days of Interferon vis-a-vis HCV are coming to a close but not soon enough to avoid irreparable damage to yet even more souls. Sure, the new cocktail is 100% effective in 8-12 weeks but they’re still not talking about that 800 lb. Interferon gorilla. What is it about Interferon? Who owns this crap that allows them to keep producing it? It’s more insidious than Agent Orange.
Within a decade HCV will become as rare as Smallpox or Polio. The cure will not entail going blind or require a few blood transfusions to “bulk up’ on your platelet count. You won’t come down with horrible autoimmune disorders secondary to the treatment either. I personally have waited for a shot (pun intended) at this Interferon-free treatment for seven years praying it would show up before I hit stage 4 or hepatocellular carcinoma- the dreaded HCC called liver cancer. With Porphyria Cutanea Tarda, the odds jump 33% higher that I’ll get it (HCC). Sovaldi is merely the cusp of the revolution. When combined with Ledepasvir, it is expected that the SVR will climb into the high 90 percentile for all the genotypes. Eventually, genotype will have no bearing in the success rate. Gilead and the other companies will keep it on the shelf for the occasional outbreak in a third world country and we’ll all breathe a sigh of relief.
Gilead had an opportunity, and indeed did trials, with a combination of Sovaldi and Daclatasvir. The results were off the chart (almost 100% again and again) but Gilead couldn’t reach a modus vivendi with Bristol Myers over combining the two and splitting the profits. Without casting stones, I suspect Gilead, like any big company, wants it’s own sole-source drug and the concomitant profits associated with it. They’re apparently right. When you have the only craps game in town and the only pair of dice, you pretty much control the horizontal and vertical. Johnson and Johnson’s Olysio isn’t going to be a serious competitor. It’s a day late and a dollar short. Besides, it’s also a retread of the Telepravir/Boceppravir protease inhibitor line of products and is yesterday’s news -like Interferon.
The new paradigm is the NS5A inhibitor which is what Sovaldi is. Daclatasvir and Ledipasvir are, too. These are just the tip of the new drug iceberg. Interferon was like the old Franchi-SPAS 12 gauge street sweeper. The collateral damage was never cataloged because they were too busy trying to prove it was the miracle cure for Hep. If a majority suffered and fell by the wayside, well, tough shit. It worked for over 34% so get over it. NS5A drugs do not run around and “shotgun” the HCV virus like Interferon did with its horribly predictable side effects. They work much like that goo you put between the shoulder blades of you dog or cat for fleas. Frontline® and its similar flea juice competitors interrupt the cycle of flea-breeding. NS5As operate identically and work much like RU-485- the “day after” pill to prevent conception. Anyone with an ounce of sense can see taking a contraceptive is far more logical than opting for a risky 1950s-style, late-term abortion in a back room somewhere with a 34% chance of terminating the pregnancy.
Having talked with over a hundred of you lucky souls who were cured on the Gilead trials, the worst side effect I’ve heard of is itching and gastrointestinal issues like flatulence. I say that beats the pants off thyroid cancer and incurable mental depression. Personally, I’ll take farts over blindness any day. Besides, for me it will be the longer 24-week course. For the majority of you, it will only be the eight, twelve or sixteen-week course. I’m stocking up on Febreeze and a back scratcher, dude.
The saddest part of this is that medical researchers were willing to sacrifice us on the altar and tell us we could hack the course and suffer no lasting side effects from the bug juice. In some respects, it mimics Thalidomide in the sixties. Little or no testing resulted in a generation of children disfigured for life. At least they were not killed outright in the pursuit of a cure for morning sickness. Small consolation in retrospect. I’m sure they’ll say the same of Interferon fifty years from now.