Date: May 1st, 2011
Exciting treatments make slowing and even restoring vision loss in wet age-related macular degeneration (wAMD) patients a reality. Two of the most frequently used treatments are currently in the spotlight as they go head-to-head in clinical trials comparing their effectiveness, and to some extent, exploring their costs.
The Anti-VEGF Treatments
AMD is the leading cause of irreversible vision loss in Americans age 60 and over. This progressive eye disease involves the breakdown of the macula—the light-sensing portion of the retina—resulting in the loss of sharp, central vision. With wet AMD (wAMD), the more advanced form of the disease, abnormal blood vessels grow under the macula, often leaking blood and fluid which damages the vision cells.
Although there is no cure for wAMD, relatively new therapies have proven to slow the progress of the disease and even restore vision in some patients. These drugs are injected into the eye where they target VEGF (vascular endothelial growth factor)—a protein involved in the growth of new blood vessels. By blocking this protein and therefore new blood vessels, these Anti-VEGF drugs are able to reduce the leaking which ultimately damages the macula.
Lucentis® is a broadly available Anti-VEGF that is considered the best treatment currently approved for wAMD. Clinical trials show that it stabilizes the vision loss of most patients and restores a significant amount of vision in around 40% of those receiving the injections.
Avastin®—a drug produced by the same manufacturer as Lucentis®—is another Anti-VEGF drug that also works by targeting that critical protein. One major difference between the two is that Avastin® hasn’t been approved by the US Food and Drug Administration for the treatment of wAMD (although it has been approved for playing an anti-blood vessel roll in advanced colorectal cancer). This means that the drug hasn’t gone through the FDA’s rigorous safety and efficacy testing for wAMD.
Despite this fact, many ophthalmologists use Avastin® when treating their wAMD patients. They defend this “off-label” use by noting the similarity of the two drug molecules, which they believe means they will have similar safety. The other major difference between the two drugs is also the reason ophthalmologists and patients are drawn to Avastin®—the cost difference. While Lucentis® costs $1,500 per injection; Avastin® injections cost only $50.
The Comparative Effectiveness Trials
There are a number of different trials taking place around the world, in the US, UK, Germany, France, Norway, and Austria, that are comparing these two drugs to find out if they are equally effective. The results from the US trial sponsored by the National Eye Institute at the NIH—CATT (Comparisons of Age-Related Macular Degeneration Treatments Trials)—will be released in early May and are expected to show that Avastin® is as effective as Lucentis® in reducing and restoring vision loss. Similar results are expected from the other trials.
While these trials are not comparing costs, a desire to find cost-savings in the treatment of wAMD is a motivator for most, if not all, of these trials. These motivations have a number of stakeholders—from patient groups to innovators—worried about what will happen with these results and what this could mean for safety, patient access to these and future drugs, and future investments in innovation.
Innovation & Access
Avastin® was developed to treat advanced colorectal cancer. In these patients, it’s administered through an IV where it then travels throughout the body and targets lurking cancer cells. Many experts believe, as did the manufacturer of the drugs, that the Avastin® molecule was too big to pass effectively through the layers of the eye in order to reach the retina and inhibit blood vessel formation. That’s why the manufacturer developed a small molecule specifically for wAMD—Lucentis®. This is also why many fear that Avastin® is not as effective as Lucentis®, and potentially not as safe. Because the CATT Trial only includes 1,200 patients, it may not be large enough to truly determine safety.
Also at issue with safety is how Avastin® is sold. Because it’s produced for cancer where much higher doses are used, in order to use it with wAMD patients Avastin® must be divided into much smaller quantities. This sometimes happens at an experienced compounding pharmacy, but often occurs right in the physician’s office. This can lead to inappropriate doses and other safety concerns
There are also concerns that if the trials find the two drugs to be similarly effective, private and public insurers could decide to only reimburse for Avastin® since it’s a significantly cheaper treatment. Decisions like these obviously restrict patient access and while most agree that with sky-rocketing health care spending cost concerns must be addressed, advocates are also concerned that this type of decision could lead down a slippery-slope where treatments are one-size-fits-all and where individual risks and needs are placed second to cost.
Advocates are also concerned about what cost-based decisions could do to future innovation. Manufacturers are obviously worried about scenarios where they spend a huge amount of money to develop a drug, only to be pushed out of the market because a cheaper alternative is determined by insurers to be the only necessary.
The fear is that this type of climate could lead to a world where manufacturers choose to only invest in treatments that are completely different from any that are currently available, and avoid research that leads to advances in existing treatments and improvements to delivery of care. This is why it’s critical that the decision to conduct these types of trials, and the decision of what to do with the results, must find a proper balance between containing costs and ensuring patient access and future innovation.
To learn more about the Anti-VEGF drugs, the head-to-head trials, and comparative effectiveness research visit the CER Repository on-line.