Noticing that her sight had become fuzzy, Lois Otto of Stuart thought she might need new glasses. She went to the doctor’s for what she thought would be a routine visit, and found out she had wet macular degeneration in both eyes.
Otto is in her mid 70s, lives alone and still works; she needs her eyesight. Luckily, because of recent advancements in treatments for this disease, she still has her vision.
Presently, Otto is part of a clinical trial testing a new drug, VEGF Trap-Eye. (If it weren’t for the drug, I’d be blind,” she said. “I go every month to Retina Care Specialists and they check my eyes. Sometimes I need an injection in the eye that is part of the study, and sometimes I need it in the other eye.
“I can tell when I need an injection because my vision gets blurry. After I get an injection, I go home and sleep, and in a couple of days, I’m seeing pretty well again.
“I can drive, I see road signs, the lights, the traffic. I’m told I’m a pretty good driver.”
Age-Related Macular Degeneration (AMD), the disease
A genetic disease affecting about 13 million people in the United States more than 40 years old, most patients diagnosed as having macular degeneration have the mild or intermediate form of the disease (dry macular degeneration). Only 6-8 percent of patients 75 years or older has the advanced form, wet macular degeneration (Otto is one of them).
Wet AMD, the leading cause of blindness of the elderly, occurs when certain proteins (vascular endothelial growth factor or VEGF) cause abnormal blood vessel growth in the back of the eye. As the blood vessels grow, they can leak blood and fluid, which damage the macula—the part of the retina that lets one see color and fine detail.
For the most part, laser treatment, which eliminates the abnormal blood vessels, is no longer used to treat AMD because it causes scar tissue. Another treatment, using light to activate the medication, Visudyne, is seldom used either. Newer medicines – first Eyetech’s Macugen, then Genentech’s Lucentis and Avastin, are far more effective, explained ophthalmologist Philip Rosenfeld with Bascom Palmer Eye Institute with offices in Miami and Palm Beach Gardens.
“In 2001, I was the lead investigator in phase 1 trials for Lucentis. The paradigm shifted. Lucentis changed everything. Rather than simply slowing down vision loss (with Macugen), we got dramatic vision improvement in a day or two. Patients were seeing better.”
Lucentis binds VEGF, stopping the growth of abnormal blood vessels (When a cut heals, it’s thanks to VEGF. In cancer, when a tumor grows, it’s also because of VEGF).
Around that same time, a new imaging modality, Optical Coherence Tomography (OCT), became available. With a light, doctors could see into the back of the eye. “This was great technology. After a patient was treated with these new drugs, with OCT, we could see where the blood vessels were and if leakage was occurring, and we could see that we were getting rid of the fluid in a day.”
Then, in 2003, something “truly miraculous” happened, he said. “And I can take credit for it.” Rosenfeld, who also has a Ph.D. in genetics, began studying Roche-owned Genentech’s literature and found that Avastin, a drug that Genentech was developing for cancer that also blocks abnormal blood vessel growth, uses the same molecule as Lucentis to bind VEGF.
Lucentis VS. Avastin
“I went to Genentech and said, patients don’t like having a needle stuck in their eye, so let’s use Avastin systemically and they said, no. They did not want to use Avastin for eye disease.
“So I raised money for a trial in Miami and Palm Beach Gardens on Avastin, systemically, and it worked great. I was convinced it would work just as well as Lucentis, without a patient needing to get a needle stuck in their eye.”
But, his colleagues didn’t want to take the 1-percent risk of heart attack or stroke with a systemic treatment (that a cancer patient would be willing to take because it would prolong life).
“Then we had the Eureka moment. We realized if we injected the same amount of Avastin as Lucentis, we would have the same amount of inhibitory activity, and it worked.
“The big difference? Once we prepared Avastin, it cost about $10 compared to Lucentis, which was $2,000.
“This was in 2005. We presented this to meetings and it spread all over the world, and Avastin was ready before Lucentis was available. Avastin got FDA approval (for colon cancer) in February 2004. We first used Avastin as an injectible into the eye in 2005, and Lucentis was approved in 2006.”
Avastin spread globally because it was affordable and it worked, he said. In the meantime, since Genentech would not do a trial for Avastin to be used for macular degeneration, the National Institutes of Health sponsored a trial to compare Lucentis and Avastin head-to-head. Results should be published either in late April or early May. “We are anxiously awaiting the results.”
Doctors are being incentivized to use Lucentis, he said. Medicare reimburses physicians 6 percent of the sales price for the drug they use, and Genentech started a rebate program for high-volume Lucentis users.
“Although that amounts to being paid double and a good sum of money, up until now 60 percent of U.S. doctors use Avastin over Lucentis,” he said. “That’s really a credit to our profession that so many doctors are concerned with saving money.”
Other countries – The United Kingdom, France, Germany, Germany, Austria, Norway and Brazil – are also conducting trials comparing the two drugs. “In early March this year, in the UK, NICE (National Institute for health and Clinical Excellence) decided that Lucentis would not be covered for diabetes (diabetic macular edema), and that’s the first example of a national health organization saying, ‘No, it’s too expensive and we are not going to cover it,” Rosenfeld said.
Meanwhile, other drugs are also in trials. One of them is VEGF Trap-Eye by Regeneron.
Dr. Adrian Lavina, an investigator in Regeneron’s VIEW 1 study, offers his patients the choice to use VEGF Trap-Eye at his practice, Retina Care Specialists in Palm Beach Gardens.
“This drug is similar to Lucentis in that it represses VEGFs, but it has a higher affinity, he said. “It binds more tightly to VEGF molecules and another molecule, Placenta Growth Factor.”
While Lucentis is given every four weeks for two years, longer periods of time can go between doses of VEGF Trap-Eye, and even though Lavina’s patient, Otto, said that the injection is painless, people don’t like getting an injection in their eye.
For the VIEW 1 study, which started about a year and a half ago, after a loading dose of three monthly injections the patient gets a VEGF Trap-Eye injection every two months, rather than once a month. Initial results were released in November 2010, and VEGF Trap Eye was found to be just as good as giving Lucentis every single month after one year of the trial.
The results of a sister study, VIEW2, were released at the same time and mirrored the results of the VIEW1 study. Now is the right time to present the drug for FDA approval, Lavina said.
Lavina uses Lucentis and Avastin for patients who are not candidates or interested in taking part in a trial. He also uses Eyetech’s Macugen, a company headquartered in Jupiter, in select cases – for high risk patients who’ve had a recent stroke, or patients already stable on Lucentis. “It’s a niche market. It also binds VEGFs, but only one isoform of it. There are five active isoforms, and medicines like Lucentis, and VEGF Trap-Eye bind to all five. “
Now, Lavina is in the second year of the two-year study, where injections are given every three months, more if needed.
“It’s very exciting to give the very best and to be able to offer medicines that are up and coming and might be better than what is currently available and we have a duty to move our field forward and be on the forefront of developing treatment,” Lavina said.
Rosenfeld, too, finds the advancements in treating AMD exciting, and he agrees that less frequent dosing is a real benefit, but he asks, what will VEGF Trap Eye cost?
That’s a big question – Lavina said, because pricing would not be released until after FDA approval.
(for follow up on costs for VEGF Trap Eye and FDA approval, go here.)
(for follow-up story on Lucentis and Avastin, go here.)
In the meantime, Rosenfeld is turning his attention to dry macular degeneration. An FDA-approved drug to block another disease (PNH or paroxysmal nocturnal hemoglobinuria), Alexion’s Soliris is under trial in his Palm Beach Gardens and Miami offices. “It’s already shown to be a safe drug, and we know the appropriate dosage and the dosing interval.”
written for palm2jupiter