It's been a while since we discussed the Avastin-Lucentis controversy, but the battle has been taken up by another blogger, Howard Brody at Hooked:
Quick overview--Genentech, the biotech firm, is maker of a very successful drug (brand name: Avastin) that is quite useful in colon cancer. The drug works by counteracting the tendency of tumors to create a lot of new, small blood vessels to keep the growing tumor supplied with blood. Some smart person figured out that the eye disease called wet macular degeneration is caused by a similar proliferation of new blood vessels and so the same sort of drug might help that condition too. (Wet macular degeneration occurs mostly in older folks but is not the most common sort of macular degeneration, a common cause of progressive vision loss. Still it affects a large number of people.)So some retinal specialists tried Avastin by injection into the appropriate area of the eye and found that it really worked just great--highly effective and apparently very safe. The special bonus was the price. Avastin is extremely expensive for colon cancer, costing many thousands of dollars for a course of treatment. But the dose you need to treat an eye is a tiny fraction of the dose you need for colon ancer. So a single very expensive vial of Avastin can produce hundreds of relatively cheap doses for eye use. (Hooked, hat tip Roy Poses at Health Care Renewal)
It was too cheap. Genentech decided to make a substitute, just for the eye, that was a lot more expensive. They got FDA approval and are marketing it under the name, Lucentis. There followed the usual marketing juggernaut to the docs to convince them that Lucentis worked better (no evidence for that, however) and that if they used Avantis off label they could get sued. Hooked reports a calculation that if everybody with macular degeneration used the hyper expensive Lucentis preps it would soak up Medicare's entire eye treatment allocation.
Now I'm of the age where I have a retinal specialist and I asked him about it. He said he was still using Avantis, breaking up the large dose into the smaller ones. Good for him. And Hooked tells us he isn't the only one:
Despite all this pressure, the obvious rightness of using the good, cheaper drug continued to win out, and a significant number of specialists were using Avastin for wet macular degeneration and passing the savings along to the patient or the insurer.
Genentech was furious that the docs were refusing to be bribed, as usual. They cranked up their campaign, threatening to cut off supplies of Avastin to anyone who was making it available for eye use. They did this of course not for slimy financial reasons, but for good scientific reasons because they wanted to promote the very best quality of care.
Genentech claims this decision was a result of "communications" from the FDA. I first wrote, "Hard to believe ..." but then decided that, no, it wasn't that hard to believe. This is the Bush FDA, after all, an extension of Big Pharma's Office of Legal Counsel.
At this point the American Society of Retina Specialists (ASRS) and the American Academy of Ophthalmology weighed in:
Last Friday, the leadership of the Academy and the American Society of Retina Specialists (ASRS) met with three of Genentech's top leaders: the company's chairman/CEO, president and chief medical officer. We had a frank and open discussion about Genentech's decision to stop sales of Avastin® to compounding pharmacies and impressed upon them our deep concern for its impact on patients' access to this treatment option. We are encouraged by the meeting results and hope our optimism will be justified by future actions.
Genentech has blinked, at least for the moment. After the meeting they agreed to delay the Avastin sales embargo to compounding pharmacies until Jan. 1, 2008 to allow time to find work-around solutions; not to impede physicians or other legal agents (e.g., group purchasing agents) from ordering Avastin or using compounding pharmacies after the embargo is in place; and to work with appropriate parties to make anti-VEGF therapy (Avantis and Lucentis) available for eligible low-income or under-insured patients.
It's a start. But I have insurance and wonder why my insurance company should pay higher prices just because I'm insured. If Avantis works, it works. And it does.
If Genentech succeeds in intimidating doctors from prescribing effective, low cost treatment for macular degeneration, a major cause of blindness amongst the elderly, because it wants to make a pot of money, it deserves to have its name dragged through the mud.
We'll be glad to help with that.
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There's one yardstick you can use to determine whether the drug is worth it, and that is cost-effectiveness. We recently published in Ophthalmology a cost-utility analysis on cataract surgery and although it's a fair amount of work, if one has the outcome data, and the charged price of the drug, one can determine if it's worth it by using the benchmarks that have been established. For example, an intervention that costs $20,000/QALY gained (QALY = quality adjusted life year) is considered very cost-effective.
Marissa: Interestingly enough NICE (the UK health technology assessment body) is in the process of conducting an evaluation of just this matter. Their preliminary judgement appears to be that Lucentis (generic name Ranibizumab) is cost-effective for more advanced forms of wet AMD with a cost-effectiveness ratio (CER) of $30-60,000 per QALY. Note that this is at UK drug prices (UKP 761.20 excluding VAT at 17.5% per injection) in the UK healthcare system, so this may not transfer directly to the US context.
However, if there is no clinical difference in outcomes between using Avantis off label and Lucentis on label, then the incremental CER of using Lucentis is infinite. And we don't generally consider that an efficient figure. So until there is some kind of evidence for improved efficacy or effectiveness for Lucentis over Avantis, there remains a case to be made for not using the former.
Glad to see people bringing attention to this. My father uses the Medical Letter to get the education credits he needs for his license. He likes to have me (not a doctor, but an ace at multiple choice questions) review his answers before he submits his tests.
I had to stop double-checking his work this summer when I came across a blurb about these drugs and, yes, a summary of a study that said there was no clinical difference in outcomes. When I saw the difference in price and the threats of lawsuits against doctors who continue to use Avantis off-label, I grilled my father to make sure I was really understanding what I was reading.
He just kind of shrugged and said that was the way things were. I had to take a break to get my blood pressure down.
There is at least one objective risk to using Avastin over Lucentis.
Avastin is supplied without preservatives in vials intended for single-use. Using Avastin cost-effectively for AMD means using a single vial for many patients. Re-using the same vial carries the risk that the vial could become contaminated with bacteria. Since there is no preservative, bacteria could multiply in the vial over time (using the Avastin as a food). This could potentially result in an intra-ocular infection for the next patient.
This sort of risk is precisely why FDA normally requires preservatives in injectable drugs packaged for repeated use (e.g. insulin).
That said, if a compounding pharmacy practices good aseptic technique, the risk should be miniscule, and wouldn't come close to outweighing the cost benefit versus Lucentis.
qetzal: Yes, you are correct about that. The solution, of course, is for Genentech to package Avastin in single use vials. Yeah, right.
For more on the head-to-head study, being funded by the National Eye Institute, please see my web Journal.
Here is the link:
http://irvaronsjournal.blogspot.com/2007/11/catt-study-update-4-avastin…
Also, more on the Avastin vs Lucentis controversy can also be found on my Journal:
http://irvaronsjournal.blogspot.com/2007/10/avastinlucentis-update-18-g…
Irv Arons
The problem with this starts with one supposition, that is that the drug belongs to the world and not the corporation that made it. Oh, I agree it should be broken up and made into smaller lots but thats not our decision now is it? We can haggle of course but Big Pharma got that way by political pressure on electeds and collusion with the insurance companies, the health care system in the US got that way because of lawyers and the torts involved. How much is a person entitled to when that drug does a job on them or doesnt produce the results its supposed to?
To be profitable it is within the purview of Genentech and any one else for that matter to sell what belongs to them, at the price they think the market will bear. Its a totally defensible position. Go in and tell your boss you arent going to go to work today for the money he is paying. You want more. He will make a decision based upon company economics and fire you. Same at the grocery. Walk in, pick up your food items and tell the checkout girl that you want that stuff to be reduced in price and in more manageable sizes. I have the number to legal aid in 50 states.
The whole comentary above is suggesting that they are doing something wrong. They arent. In 06 they spent 19% of their total net sales in R&D and the stockholders are entitled to the benefits of what they sell. They raised the shareholder value per share by 1.97 but that was only 15% of the total sales diluted and after all liabilities were factored in. They have several hundred million outstanding shares.
It pisses a lot of people off that drug companies make a lot of money, but they spend a lot of it getting there too. After a few years it becomes generic and they have to go back to the boards to make a new cash cow. Genentech MADE 7 billion dollars and change in 06, they spent 6 billion and change getting there. They sold those shares to get into the business and in business you make MONEY! What a horrible concept.
You made too much money on this product so I think you need to sell it more cheaply...and right damned now!
Sanofi-Pasteur also cranked it up on the EU and the US. They are all the same.
I am defending them only in their right to make money just like you or me not in the rabid anti-incentive diatribe above. They have one hell of a lot of mouths to feed in their business and none of this is cheap. If they want to sell THEIR product as any other company then they should be allowed to do so. Just like you sell your car. Its YOURS and not someone elses. Lets keep that in mind.
What is suggested here is a taking. Force them to sell it at a level that is not cost effective or is detrimental to the health of the company that spent all the money, time and effort to make it. Its like graduating from medical school and then a socialist steps up and says you are going to make this much, you will report at this time, and you will like it.
Is it immoral or wrong that this doesnt conform to the thought that this should be made available to the public cheaply? Who the Hell made the product and by what law or right can anyone say anything different? Is it another attempt to redistribute the wealth? Remember the drug was generated by the incentive to rise higher and improve. What is suggested is that someone would take that away and by force it sounds like. We can go around and around but BF is a good example. The initial vaccine that works will be so expensive that only a few will be able to afford it anyway. Why? LIABILITY FOR STARTS, then there is the effectiveness and backend side effects. What is suggested above ensures there would be NO incentive to make new vaccines and drugs. Why? Because no one would make any money off of it. It would be too expensive, have too much liability attached to it and that would apply to every other drug out there too. Not to make it a UHC issue but they would never field it. Why? By the time it got out there the population wouldnt be there to take it. But it doesnt matter, Big Pharma wouldnt even try.
The market should always determine the price of any product or service. That means drugs are a product, healthcare is a service. Neither are rights. Nor is there a right to force a company or person from their property. Again, keep it in mind. Write letters to the company and ask, dont tell them what you think needs to be done. Also write a letter to your Senator and Congressman and ask NOT for government controls, but for a cap on liabilities for drugs and medical malpractice.
Guy, thanks for the heads-up; will be interesting to see where the numbers fall.
M. Randolph Kruger appears to miss the point.
Avastin will continue to be used to treat colon cancer, and make money for Genentech, just as intended. It appears that Avastin is also useful to treat macular degeneration at very low cost. Note that using it to treat Macular Degeneration is not going to cut any of their profits on colon cancer treatment. On the face of it, this move to deny anyone the use of Avastin for treating Macular Degeneration appears to be primarily a ploy to preserve their market for fantastically expensive Lucentis, and incidentally, deprive poorer sufferers from an affordable and effective treatment.
Our host may have missed the bullseye, too:
From what I've been able to find on the web, it appears that Lucentis was already in trials when Avastin was first being used to treat macular degeneration, so this suggestion of greed seems a bit exaggerated. In 2005, a news item on Lucentis appeared, and mentioned testing of Avastin, "But a tiny amount of the drug has been injected directly in the eye in five patients and was effective at controlling the new blood vessels in wet AMD."
According to an article on a site called HealthDot, Lucentis costs about $2,000 per treatment, while Avastin costs about $20. Lucentis, at 0.5 mg, is recommended for intravitreal injection once a month. Note that this reduces to about $4/microgram. Medical News Today agrees with those figures. It also reports "According to Bloomberg/Times, the study could "jeopardiz[e] almost $1 billion in estimated annual sales" of Lucentis for Genentech (Bloomberg/Los Angeles Times, 10/3)."
Another report from 2005 reported that Lucentis appeared to be quite effective in treating wet macular degeneration. At that time, it also reported "It will probably take a year and a half for Lucentis to be approved by the FDA." It also pointed out that "Avastin is the parent molecule for the smaller Lucentis. Genetech originally split off the smaller Lucentis fragment from the larger Avastin molecule because they thought Avastin was too big to penetrate the retina."
Note: they were wrong! --and apparently didn't even try.
Note that the consumer's out-of-pocket expenses for the portion of Lucentis that Medicare does not pay for are a multiple of the entire cost of treatment with Avastin for the same condition.
No Dan, I didnt miss it. I just wanted to make the point that if it was one dollar or ten million its THEIR product and the Constitution of just about every country states for the better part that no person (corporation) shall be deprived of life, liberty, pursuit of happiness AND property without due process of law.
The assertion is that they should be forced to break it up into more marketable dosages. Cant do that wihout a law. So if we get into the just make a law deal as the Dems did in the 60's to late 70's making just about everything subject to governmental intervention we will be up crap creek without a running Johnson. They will simply move all production off shore and put thousands out of work. The idea though is that "we should just work it out with them." No way! It doesnt belong to the leftist idea or the rightist one both of which are deemed as government in the US. Its decreed in the law. It just IS theirs to do with, and sell it for whatever they think the market will bear. I dont gouge when there is a disaster for my services. Indeed I drop the prices because I make a lot of dinars off of it. But I dont have to.
Indecent profits? No, they pay income taxes too. Its the class warfare thing and it makes me puke. Hundreds of millions in fact last year. No one ever mentions how much they pay, their employees pay and how much you can lose if those things suddenly get legislated out. Those same taxes that government would take to go and make it somewhere would be gone. No one paying into the system because the jobs are gone. Now how are they going to pay for the socialist idea? Gasoline tax..., groceries tax. Oh, cant have socialism without taxes and A MANDATE, that ensures control.
No Dan, I see what you were saying and I appreciate the idea. If there was a way then it would jump up and bite us. I am feeling pretty good about the chances of it not happening right now.
Does anyone know of the workarounds that ophthalmologists will use to get Avastin after the sale embargo begins January 1, 2008?