In an ideal world the drug industry identifies a disease, develops a cure through research and markets it to a ripple of applause. In the real world things are often a lot messier. But seldom are they quite as confused as they are in age-related macular degeneration, the most common cause of blindness in the UK. A new treatment exists that is eminently affordable, apparently safe and backed by a growing body of evidence that it works.
But the drug company that owns the rights in the UK cannot even talk about it, and — for commercial reasons — the US company that originally developed it will not be promoting it. Nor is it being taken up by the NHS.
As a result, thousands of people who develop the “wet” form of age-related macular degeneration (AMD) are being denied access to a promising treatment. Yet nobody, really, is behaving improperly. There are no villains in this story, just a lot of patients who may feel that the system is short-changing them.
The problem is real and urgent. Half a million people in the UK suffer from the condition, according to the Macular Disease Society. For most — those with the “dry” form of the disease — there are no treatments and no prospect of any. But for the 10 to 15 per cent who suffer from the “wet” form, which progresses more quickly and damages sight more profoundly, there are hopes.
AMD is caused by damage to the macula, the part of the retina responsible for precise vision. In the wet form, abnormal blood vessels grow behind the macula, leaking fluid and blood and causing rapid damage. Wet AMD is responsible for only 15 per cent of cases but it causes 90 per cent of the blindness. There is one treatment for wet AMD; Visudyne, licensed and approved for use in the NHS by the National Institute for Health and Clinical Excellence (Nice). It is not hugely effective and certainly not a cure, but it can help to slow the disease.
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Typically for a new medicine in the NHS, Visudyne was slow to reach any patients at all. And although there are now 50 specialist centres set up to provide the treatment, by last November a survey found that only half of the new patients were getting to the clinics in time to save their sight.
Visudyne is marketed by Novartis, which has also bought the UK rights to what appears to be a better treatment, Lucentis, developed in the US by Genentech. Lucentis works in the same way as some of the latest cancer drugs, by preventing the growth of the new blood vessels that cause the problem in wet AMD.
Lucentis is not yet licensed in the UK, but even when it is it will be expensive, and Nice approval will be needed before the NHS will agree to pay for it.
The same applies to another new treatment, Macugen, which does have a UK licence. On past history, the price of both is likely to prove a major obstacle: Lucentis is expected to cost more than £1,000 a treatment and Macugen £4,000 a year per patient.
So far, so familiar; but there is another dimension to the story. Genentech is also responsible for a colon cancer drug, Avastin, which uses the same mechanism as Lucentis but is far cheaper. A few eye surgeons, first in the US and now here, have been using it to treat wet AMD. The results, they say, are excellent.
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Shirley Davis, a retired NHS radiographer from Huddersfield, is one of the patients treated with Avastin in the UK. Wet AMD developed in her left eye five years ago and she was told then that nothing could be done. Recently her right eye began to deteriorate, too, and she faced the prospect of going blind. She is being treated privately at the Yorkshire Eye Hospital in Apperley Bridge, West Yorkshire. So far she has had one treatment from a surgeon, Shafiq Rehman, who was delighted with the results.
“I was very impressed,” he says. “Ordinarily, after AMD treatment you don’t see any effects when you look into the eye. But I am seeing real changes, less swelling and bleeding, the normal signs of wet AMD. I’ve treated only a handful of patients but 30 to 40 per cent have shown vision improvements. And so far, based on US experience, Avastin is safe. That’s important, and it works very well.Maybe Lucentis will turn out to be the gold standard but my guess is that Avastin is not far behind.”
Shirley Davis is unsure whether her sight has improved and is less excited than Mr Rehman. “He was jumping up and down,” she says. “It cheered me up. Maybe I was expecting too much, I was hoping for a miracle.” But she is encouraged enough to go back for further treatments and her main complaint is that after a lifetime of work for the NHS, she is having to pay for it privately. “I worked for the NHS and now they won’t treat me,” she says. “That makes me cross.”
Several other eye surgeons are using Avastin, all privately. Michael Lavin, consultant ophthalmologist at Manchester Royal Eye Hospital, calculates that the savings are huge. Avastin, he says, is 150 times cheaper than Lucentis: “Avastin is as effective as Lucentis and at least as safe, with safety data on almost 8,000 Avastin injections into the eye compared with Lucentis data on less than 800. It is highly effective, prevents blindness and is much cheaper and more effective than existing NHS treatment.”
Richard Gregson, consultant ophthalmologist at Queen’s Medical Centre in Nottingham, agrees that it is just as good as Lucentis. “But it is never going to be licensed for use in the eye, because that would need expensive clinical trials. It wouldn’t be in Genentech’s interest to conduct such trials and nobody else will do it,” he says.
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“The NHS used to conduct trials but it’s impossible now. The NHS has almost abolished clinical research of this kind by bureaucratic obstacles and lack of funding. It has always been backward-looking, having to be dragged kicking and screaming to introduce new treatments. There’s a culture of ‘don’t do it’.”
The problem for the NHS is that Avastin is not licensed for use in the eye. In medical parlance, it is being used “off label”. For that reason, Roche UK says that it is unable to comment on its use. Genentech, which markets Avastin in the US, says that it has no plans to block its use in macular degeneration. A spokeswoman says: “We have not done any testing or pre-clinical work on the use of Avastin in macular degeneration.
“We don’t know the right dose, or the pharmacokinetics (what happens to the drug after it is injected). Patients should know that Lucentis has been through trials and is formulated for the eye — it is purer and contains fewer particulates.
“We have been studying Lucentis since 1999. For us to go back and test Avastin in the same way would involve several expensive trials, with no indication that it would be any better than Lucentis.”
Doctors are permitted to prescribe medicines without a licence and the practice is quite widespread. Many medicines are used for conditions for which they do not have a licence. That is what enables ophthalmologists to prescribe Avastin privately, after explaining the circumstances to their patients and getting informed consent. So far, Mr Lavin says, only one patient has refused since he started using Avastin last October.
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His results have been excellent, he says. One patient was treated three times with Visudyne in the first eye that developed the condition, but he was still losing his sight.When the second eye lost vision, he came to Mr Lavin and was given a single injection of Avastin. Within a week he had recovered enough sight to drive.
Most of the clinical data comes from the US, where Dr Philip Rosenfeld and his colleagues at the Bascom Palmer Eye Institute, in Florida, pioneered the use of Avastin in AMD. In April, Dr Rosenfeld reported that 44 per cent of the patients whom he had treated had shown improvements in vision — this in a disease for which the best previous treatment had done no more than slow the deterioration.
Experience of more than 5,000 patients around the world indicates that it is safe. And a survey by the American Society of Retinal Specialists in March found that 92 per cent of those who responded found it “somewhat better” or “much better” than other treatments.
“With a cost difference of more than 100 times and with similar outcomes, it is clear that a large number of people could be treated effectively at modest cost by using Avastin,” Mr Lavin says.
“Waiting will cause many people to suffer permanent or irreversible blindness. It is not ethically or morally justifiable to withhold an effective remedy from people with a serious disease.”
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The problem is that the NHS is very reluctant to use a drug without an appropriate licence. “Several months ago I contacted all members of the British Vitreo-retinal Society and found that by February 2006 none had obtained access to Avastin for their NHS patients, despite many requesting this,” Mr Lavin says.
So there it is: a disease in desperate need of treatment, a drug that works and is affordable — and yet patients are still told that they cannot have it. It would be easier if there was someone to blame, but there isn’t. Everybody is behaving properly. Yet the patients are losing out.