So, I realize the vast majority of my readers don’t want to hear about my personal health issues – y’all can skip this post. But, to be honest, I’ve spent much of January in doctor’s offices or hospitals and many of the topics I’ve been following most closely are medical ones. And now I find myself very interested in a bit of a medical controversy, a controversy involving a drug I’m hoping to have injected in my eye in about a month.
I’ve been a type 1 (juvenile onset) diabetic for 21 years. I monitor my diabetes very closely and am in “tight control” (hgbA1c = 5.3, for you diabetes geeks out there). But, like a lot of diabetics, I’ve been having problems with diabetic retinopathy. For those unacquainted with this charming disease, it’s the result of the degredation of very small blood vessels in the retina of the eye. Excess sugar in the blood causes the vessels to swell and degrade. Parts of the retina get insufficient oxygen, so the body responds by trying to grow new vessels on the retina. Unfortunately, these new vessels are fragile and malformed – they have a very high chance of breaking and causing bleeding within the eye, which can cause vision loss or blindness. Diabetic retinopathy is the leading cause of blindness in adults.
Once this sort of retinopathy – proliferative diabetic retinopathy – starts its course, the major weapon you’ve got to preserve your eyesight is “photocoagulation”. This procedure involves shining a green laser through your pupil to cause burns on the retina. These burns kill off the new blood vessels – the opthamologist doesn’t target the center of the retina, just the periphery, which means it damages your peripheral vision, though not the central vision.
I’ve had eight photocoagulation treatments done over the past year, with another scheduled for tomorrow morning. They suck. Everything you read about the procedure suggests that it might be “uncomfortable” – believe me, when the laser hits a branch of the optic nerve, it’s more than uncomfortable. I’ve learned to prepare for treatments with a large dose of aspirin and a shot of whiskey before I get into the operating room… I actually have formal medical instructions telling me to drink a shot of rye half an hour before the treatment.
Photocoagulation kills off the blood vessels, but it doesn’t stop them from regrowing. In most diabetics, you fry a few thousand holes in the retina and tell the patient to get their blood glucose under control in the hopes that vessel growth will slow. But my glucose is about as good as it’s going to get, and we’re starting to look for other options. One (really bad) option is vitrectomy, the surgical removal of the vitreous humor that fills the inside of your eye. While the surgeon is scooping goop out of tiny incisions in your eye, she scrapes the new vessels from the retina. This is very effective – very few people experience new proliferation of blood vessels afterwards – but it’s major surgery, and something I’d very much like to avoid.
Doctors have been wondering if there’s a way to turn off blood vessel regrowth in retinopathy patients. They’re focused on blocking the effects of a protein called VEGF (vascular endothelial growth factor) which promotes blood vessel growth. There’s a bunch of drugs that block VEGF – most of them need to be injected into the eye, close to the retina, to be effective. Two of the most effective drugs are made by Genentech – Avastin, which was developed as an anti-cancer drug, and Lucentis, which was developed specifically for use in the eye.
The drugs work through similar mechanisms and are chemically similar, though the drug in Lucentis is a smaller molecule. Genentech believes this means that Lucentis will bond more tightly to VEGF (a good thing, as that’s what we’re trying to block) and will leave the system faster than Avastin (a good thing, as it lessens chances of side effects.)
But there’s a major reason that people want to use Avastin instead of Lucentis – it costs $50 a dose, as compared to Lucentis, which is priced at $1950 a dose. And eye doctors believe it’s as effective as Lucentis, possibly more effective.
What you’d really like to do in this case is a side by side study of Avastin versus Lucentis to see whether there’s really a measurable difference in efficacy and safety between the drugs. But Genentech has made it clear they’ve got no interest in running that study. Why should they? They’ve spent millions of dollars developing a drug specifically for retinopathy and macular degeneration – sure, it’s expensive, but it’s far cheaper than fitting your computer out with a braille reader, or getting another half dozen sessions of photocoagulation.
Most of the patients who would be receiving Lucentis are elderly. Many of those patients are on Medicare, which means the $2,000 per shot is financed by the US taxpayer. This is likely one of the factors that inspired the National Institutes of Health to run a side-by-side study of the drugs, estimated to cost $16 million over the course of four years. The cost difference per year for American taxpayers, if Avastin were available for this use, is estimated at $5 billion.
NIH says that they’re not performing the study for cost reasons – their reason for the study is that an uncontrolled study is already taking place, with opthamologists purchasing Avastin and using it in an off-label use instead of Lucentis. (This off-label treatment is something I’m currently scheduled for late next month.)
Genentech is evidently pretty pissed that a US government agency is running a drug trial instead of allowing them to choose whether or not to test a drug for a particular use. Irv Arons, who writes about opthamology issues on his blog, quotes a report from an American Academy of Opthamology meeting:
Industry entities (pharmaceutical and device companies in general – not just Genentech) reportedly are attempting to prevent the newly announced head-to-head trial sponsored by the National Eye Institute (NEI) of Genentech’s Lucentis and Avastin in AMD. Dr. William Rich, an American Academy of Ophthalmology legislative expert, said, “We are very concerned about an intervention of industry into getting this trial carried out…We are monitoring it very carefully…We do anticipate some interference with the start of this trial by industry…Industry is going to petition not to see this trial carried out…I wouldn’t be surprised (to see the trial stopped). And public interest groups (e.g., AARP) around the country are going to be watching carefully, too.”
I’ll be watching, too. I understand and respect the need for pharma companies to recover their research costs. I understand that having Avastin approved for this use would likely cost Genentech billions of dollars and would likely tank their stock price. (My opthamologist has advised me to short Genentech based on this controversy…) But given the cost differential and the fact that many opthamologists are already using Avastin, it seems pretty churlish to try to block this study.
Even if I’m able to scrape up several thousand dollars a year to afford monthly Lucentis injections (my HMO is unlikely to cover the full cost of the drug – Medicare covers less than a third of the cost of Lucentis), diabetes is a global disease that’s growing quickly. Doctors in middle income nations aren’t going to be able to persuade their patients to use a drug that costs over $10,000 a year. They’re going to use Avastin, for a few hundred dollars a year. Which means that it would be a really, really good idea to do a systemic study on the use of the drug to make sure that it doesn’t cause brain warts or the unexplained dissapearance of fingers and toes somewhere further down the line.
I trust the doctors who’ve been treating me. They haven’t even put Lucentis on the table as an option, possibly because they’re sufficiently antagonized by Genentech’s behavior. If they think Avastin is safe enough to inject it into my eye, I’m willing to give it a shot. Here’s hoping the National Institutes of Health will be able to tell me if I made a bad mistake in about four years.
We met at a conference in Madrid a while back and I was then as now in awe of your accomplishments and good works.
Just wanted to say I have my fingers crossed for you and thank you for sharing your travails so the rest of us can cheer you on.
With all best wishes,
Hey Ethan –
Even in the midst of surgery, you’re still blogging, analyzing and expanding our world. Hang in there.
All the best,
Glad of an update over here too.
And for the love of — I think someone owes you a rebate on about six months out of the last twelve, a glass box for the mantle shelf, with a preserved sennite or six for when you need them…
Anyway, may not be making much sense, but thinking of you. Take care.
I love how you share your life. In the dentist’s chair yesterday morning I wondered why I hadn’t had a shot (or three) of whisky.
Love from Zimbabwe
What a scary thing to deal with. All best wishes for the best possible outcome!
I wanted to hold forth on this sentence: “I understand and respect the need for pharma companies to recover their research costs.” As usual, you’re way too tolerant and kind.
I’m not a biomedical researcher, but as a biologist I’m close enough to the field to be reasonably familiar with how research into new drugs works.
1) The lion’s share–and this is a pretty big lion, about 90% I believe is the number–of basic, groundbreaking research for new drugs is done on government grants. Ever since Reagan’s day, the costs have been socialized while the profit has been privatized. This is supposedly necessary to give private enterprise the incentive to develop new drugs. And yet, funding for basic research continues to be almost entirely government-funded. In other words, you’ve paid for that part already.
2) The applied research carried out by industry is sometimes useful, but also includes things like figuring out new methods of drug delivery so that a profit-making drug due to go off-patent can be repatented in the new package. A recent example is Prozac, which appeared in a once-a-week dose to replace the usual daily dose just before the patent expired on that.
3) Some large proportion of the industry’s new drug costs (30%?) are marketing.
4) Doing the required clinical trials to bring a drug to market really is hugely expensive, and is something the industry can validly whine about.
5) Investors are an impatient lot. They want those “research” costs recovered as quickly as possible. I believe, ideally, that’s supposed to take no longer than 3-5 years. (17-year patent, and during the majority of that time, the money coming in is preferably pure profit, right?) Well, if industry insists on recovering the hundreds of millions of dollars spent on clinical trials and marketing (with a bit of research thrown in) all within a few years, then it’s no wonder that the so-called research costs are staggering. They could also amortize them over, say, twenty years. I’m not sure why it’s up to sick people to pay the price of the industry’s churlish business model. And of investors’ greed.
To hear, on top of all this, that these companies have the sheer, downright, vicious dishonesty to try to obstruct OTHER PEOPLE from doing research and comparisons — well, words fail me.
There was a parallel case a few years back with TPA (clot-buster drug) and some cheaper alternative that the Europeans were comparing. I think that was Genentech, too. Whichever company it was, they tried to stop the study, but couldn’t since it was backed by a foreign government. The result? Something like a 2% difference in effectiveness, for a 10-fold difference in price.
I’d be willing to bet they’d be less obstructionist about the Avastin study if they didn’t expect the same type of result.
Sending you the love from Toronto, Ethan – as always. Do you get a prescription for more whiskey afterwards?
Sorry for your travails — you should be able to find an ophthalmologist who will inject Avastin (at $50/dose) plus his fee. There are many around the country who are doing this.
I’m also hoping that via blogs like yours and my contacts with several journalists, to get the story behind the controversy uncovered — who really is behind the efforts to stop the comparitive study?
Thanks for mentioning my blog. I expect that several of your readership will take a look at what I’ve been writing about Avastin and Lucentis.
Best regards (and good luck),
I hope today’s round of zapping was . . . only as uncomfortable as necessary.
As someone whose role regrettably involves increasing pharmaceutical transaction costs (but doing other things that I think are good for the world), stories like this gall me particularly. And it’s amazing how often Genentech’s name comes up on the wrong side of them. I don’t doubt that there are plenty of other baddies out there (maybe most of them, in one way or another), and I know there is almost sure to be moral ambiguity to any situation involving pharmaceuticals, but at some point it stops being a coincidence, I think.
Anyway, good luck with the next round.
I fortuitously happened upon your post via the Nonprofit Blog feed. My mother-in-law who has diabetes just had a blood vessel burst in her retina a few weeks ago. When it happened, the doctor gave her an injection of what must have been Avastin (he said it was a drug used for colon cancer). Yesterday, she had the laser treatment. Thank God, she went from not being able to see well enough to read to being approved to start driving again as a result of these treatments. Thank you for providing such a clear explanation of how this problem occurs and its treatment — you’ve given me a much clearer understanding of what’s been happening with her, and I just sent her a copy of your post to read.
Best of luck to you with your treatment.
Thanks for the support, everyone. Yesterday’s surgery was fairly uncomfortable, but I’ve got high hopes it’s the last session for some time to come.
Nedra, I’m very happy these words were useful to you as your mother in law faces surgery. It’s remarkable how much has been achieved in the field of eye surgery in the past 30 years – she would have lost vision in that eye just a few decades ago. Let’s hope that medical advances mean that the lasers and needles are unhappy memories in another thirty years.
Quixote, I’m tempted to agree with most of what you’re saying – my problem is that I’ve also looked closely at the financials of pharma companies that are struggling, that aren’t spending huge sums on marketing and don’t have cash cows like Prozac to monetize. I think it’s really important to ensure that pharma companies have sufficient financial incentive to work on diseases that wouldn’t otherwise be a major focus.
That said, I can’t help feeling that Genentech made a poor pricing decision on this drug and is going to have that decision bite them in the ass. When someone’s going blind, $50k for treatment in both eyes is a sum that many people in the developed world will find a way to pay. But that doesn’t mean it’s right or ethical to charge that amount if the price of producing the drug is significantly lower (which I suspect it is.) Betsy – who knows a lot about this world – offers an intriguing comment about Genentech – I’ll be interested to see if that impression is more widely shared…
Thanks, everyone, for the comments and support.
Thank you for posting your information on retinopathy treatment. My huband was just diagnosed today, and we will be meeting with his doctor next week to discuss treatment options. Possibilities mentioned include laser, injections, and possible participation in a clincal trial (we don’t have any specifics yet). Your post will certainly help us in formulating questions about his treatment.
As far as Genetech is concerned, I suppose we shouldn’t be surprised at their actions. After all, we live in the USA, where the profit margin is the moral compass.
Good luck in your ongoing battle with retinopathy. There is hope that with so many people with the condition, newer, more effective, and more comfortable treatments will be a priority in the research community.
Thanks again for your information,
I had diabetic retinopathy bleeding late Nov. 2006 in my “good’ eye. Having had numerous laser surgeries on my right eye, I knew the end result of that! That laser permanently removed enough of my sight as it coagulated the bleeding blood vessels that I am legally blind in my right eye. So, having been there, done that, I was not anxious to do the same in my left eye. Even though I had questioned my specialist many times before when he was doing laser on my right eye, the option of just waiting it out had never been presented to me. This time, I chose to wait it out. Now in middle Feb 2007, my eyesight is slowly improving in my left eye w/o laser. From an 80% loss of vision, I can now see almost everything. Still some cloudiness to needs to clear up, but slowly everything is becoming clear! Since the eyes regenerate their own blood vessels and since I have tight control of my Ha1C (4.4), I decided to give them to regenerate and that they would be healthy. So far, so good. I am taking vitamins that are supposed to help in eye health, lutein, e, a, c and fish oil. I did find support on the internet regarding waiting it out. Is there anybody else that has chosen to wait it out?
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here’s the audio from an interview i did with Dr. William Rich from the American Academy of Ophthalmology on the head to head trial between Lucentis and Avastin.
i’m going to talk to someone from medicare next week on the delay to funding the research. more to come…
My mom is a 65 y/o diabetic with all sorts of complications such as heart muscle issues, incontinence, leg/foot ulcers and neropothy of tissues, and now she has lost her sight from diabetic retinopathy and blood hemorrhaging. The doctors want to try Avastin for treatment in Detroit, but claims that it is $300 per injection. He did not mention Lucentis at all. My mom only has Medicare at this time and I am wondering why he did not mention a drug that was approved and covered?
I have just had my fourth shot of Avastin. I went from barely seeing anything in my one good eye, to 20/25 at my last exam. My left eye is legally blind as a result of myopic macular degeneration occuring about 10 years ago.
It was a miracle for me to go from VERY dim vision to where I am today. Unfortunately, a blood vessel was broken this time, and there is still blood showing in my eye. Today the news that Avastin has been dropped from lung cancer trials because of patient’s extreme reactions and even death. I wonder if there is a down side to the injections in the eye that are now known or being discussed at this time.
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It’s been a while. I hope that you get the best procedure for your eye.
Your ailment makes me appreciate the little that I take for granted everyday.
This is an ongoing controversy for some time now. My mom was treated with Avastin because Lucentis was not approved or available at the time. Now it’s been a year later and the progression of her disease has halted, which is great!
Hi my husband is diabetic and just been told that avastin is no good for diabetic macular oedema he has had no treatment on his eyes for over 6 months as they kept losing his records we are now being told his vision is so bad he cant drive if someone could help us i would be grateful
i am not diabetic but i had a retinal branch vein occlusion 8 years ago. have had numerous laser surgeries for retinal bleeding. for the last two years i have had macular edema due to fluid back up in the macula. i had seven avastin injections over a period of 15months. they were quite expensive, not covered by insurance, and not that effective. took 3 weeks to work, bought me a month of clearer vision and then desired effect started to wear off. within 3months after injection fluid buildup was worse and required another injection. about 9months after the first injection my sense of taste changed. things started to taste tainted. i totally lost my taste of wine – it all tasted bitter. during that time i also noticed that my beautiful skin started to look withered and my hair started to fall out. one day, after the seventh shot, i sat down and asked myself “what is different ?” i realized that the only thing different was the avastin. i researched side effects with intraoccular injections. no info on whole body sides effects with local application. also my retina specialist had no info. when i researched avastin sides effects as a chemo drug – there were my symptoms. i refused more avastin. i have since had an ozurdex implant and it has worked very well almost from the start. three months later it is still working. don’t know if that would solve your problem but if you choose avastin be prepared for significant side effects beyond redness at the sight of the injection and infection. oh and it was at least four months afer the last injection that my skin started to look good again, hair is doing better (but not great) and hada glass of wine saturday night. tasted great.
I received Avastin shots in my right for diabetic retinopathy/macular edema(once a month for 8 months) – H1ac 6.0. Initially the symptoms were suppressed for 30 to 32 days, but by the end of 8 months it was lasting only 22 days. I’ve received monthly shots of Lucentis for the past 2 months and it seems to be woking the full month. Next month I will be getting shots in both eyes.
A couple of diet changes also impacted effectiveness, no nitrates/processed lunch meats, reduced red meat consumptions, taking fish oil supplements.
Hello, I am reading this to help y Dad. He has diabetic retinopathy and practically can’t see, just shadows ,I really want him to try either Avastin or Lucentis. He has lost faith that he can see again, but I haven’t. He lives in Peru and recently both injections are available. I dont want to give him too much hope that he would see again, but is there anyone out there that have tried any of this medications and was able to see clearly – from almost blind condition?
Please advice, getting my father to get into this treatment is expensive plus I dont want him to get depressed if it doesn’t work.
Thank you in advance!