I presented the exciting results of our novel treatment strategy for diabetic macular edema at the World Ophthalmology Congress in Abu Dhabi, United Arab Emirates.  The strategy is RaScaL, or Ranibizumab plus Scatter Laser.

Our study demonstrated that patients with diabetic macular edema and damage to the peripheral retinal vessels (peripheral nonperfusion) imaged on the Optos P200Tx Instrument have a better and longer-lasting response to a new treatment strategy of laser to the areas of poor circulation in the peripheral retina and intraocular injection of lucentis.  In the trial, patients treated with conventional treatment had an 80% recurrence rate needing retreatment before 6 months.  The RaScaL treatment patients only had a 33% recurrence rate at 6 months.  The study was conducted at Retina Associates of Florida, and was sponsored by Genentech.  It used a unique instrument, the Optos P200Tx to image the peripheral retina to classify the patients and direct the laser treatment.  Retina Associates of Florida and Dr. Suner have been involved in the development of this instrument since 2003 and are one of only a few practices across the country to have this instrument.

Eylea (aflibercept, Regeneron) just received FDA approval for treatment of Wet Macular Degeneration.  It is being billed as better than Lucentis and Avastin because “it lasts longer.”  Is this true?  Will it replace Lucentis and Avastin?  What are early issues with using this medication?

Eylea works by a similar mechanism as Lucentis and Avastin (blocks Vascular Endothelial Growth Factor or VEGF).  Instead of being an antibody to the VEGF molecule, it is a fusion protein consisting of portions of the receptors for the VEGF molecule (VEGFR-1, VEGFR-2), thereby binding and blocking VEGF.

The results of their pivotal FDA studies (VIEW 1 and VIEW 2) showed that 1)Eylea injected every month, 2)Lucentis injected every month, and 3)Eylea injected every month for three months then every two months after that had very similar results at one year (see Table below):

To summarize, the three groups gained between 8.4 and 9.25 letters (almost 2 lines of vision) at one year.  There were no significant differences between them.  Biggest problem:  there was no comparative group of Lucentis every 2 months.  So… we really don’t know if Lucentis every 2 months would be the same.

So, there is no clear evidence that this new drug is more effective than Lucentis.  The price is also similar to Lucentis (about $1,800 per injection).  Even though it is approved for every two months, it can be used every month.  Their Year 1 to Year 2 extension study (using treatment when there is leakage), showed Eylea patients needed an average of 4.2 injections while Lucentis patients needed 4.7 injections (not a big difference).  Also, when treatment was done “as needed” instead of on a regular monthly schedule, patients lost about a letter of vision.

Best use for this drug:  current Lucentis or Avastin patients that are not effectively controlled on current regimens

Biggest problem:  Because this drug is new, it does not yet have its unique “J code” for reimbursement.  As a result, it may be tricky to get your insurance company to cover it and you may be stuck with a big bill.  This will likely improve with time when it obtains a J code.

BOTTOM LINE:  Eylea is a new drug for Wet AMD that may be helpful in patients that do not completely respond to Lucentis and Avastin.  It has the potential to last longer than Lucentis and Avastin, but so far the evidence is not terribly strong and the visual acuity results are not different.  Currently, obtaining insurance coverage for the drug may be challenging as it does not yet have a J-Code.

Why, if they are so similar and made by the same company are the costs so different?  The answer is actually quite complicated.  In reality, a dose of Avastin for its true indication (cancer) is about $3,000.  What happens is that when it is used for treatment of retinal conditions, a compounding pharmacy prepares and aliquots the doses for eye injections (50-60 doses in one vial of Avastin).  That is why the cost for a dose for eye treatments goes down.  Therefore, Avastin is an anomaly that is quite unique in medicine.

This brings up the question: Why are drugs so expensive anyway?  The answer here is that the government, in other words, the Food and Drug Administration (FDA) requires a complex and expensive process for drug approval.  It is estimated that the cost of developing a drug and making it through the FDA process costs between $800 million and $1 billion.  If one then factors in that less than 10% of drugs developed are approved by the FDA, then one sees that developing a drug and getting FDA approval is a high stakes, risky proposition.  So, when a drug company prices a drug, it factors in the costs of development, FDA approval, and potential earnings of that drug, but also of other drugs that did not make it through the process.  If drug companies could not make a return on their investment, drug development would end and we would see the end of new therapies for the many unmet medical needs.

BOTTOM LINE:  We prefer to use an FDA-approved drug when it is available and covered by your insurance because: 1) it shown to be safe for use in the eye, 2) it is the “right” thing to do to allow the drug development process for future therapies.  The cost issue stems directly from the government’s process of drug approval, and should not factor into a physician’s decision in providing the best care for a patient.  The issue of cost should be addressed by the government and the pharmaceutical industries to allow for cost-effective medical care in the future.

How do they work and why was a cancer drug used for the eye? Both Lucentis and Avastin block Vascular Endothelial Growth Factor (VEGF), which is the predominant molecule resulting in leakage, bleeding, and growth of abnormal, destructive blood vessels in the retina. Both drugs were developed by the same company, Genentech, but they were designed with different specifications for different reasons.  We saw spectacular results of Lucentis treatment for wet AMD, but it was not yet available due to the FDA review process.  Avastin is an FDA-approved drug for treatment of some cancers, and was approved before Lucentis.  During this window before approval of Lucentis, Avastin was successfully tried in an off-label use. Since we knew of the spectacular results of Lucentis in clinical trials for wet AMD but it was still being reviewed for approval by the FDA, retina specialists tried using Avastin in an off-label form.  This proved to be a wonderful option for our patients during this period of almost a year as there was no better treatment.

How are they different?

Avastin is (1) a much larger antibody that was developed for cancer treatment.  It was developed as a larger molecule to stay in the circulation longer to fight cancer cell.  This longer duration, however, could in theory, have a higher risk of high blood pressure, heart attack, and stroke.  It is (2) manufactured for injection into a vein, not the eye, so the preparation standards are not as strict as in Lucentis, which has to meet higher standards of purity for injection inside the eye.  As a result, there may be contaminants that can cause inflammation in the eye, which see in some patients.  Also, (3) it has to be mixed, diluted, and aliquoted in a commercial pharmacy and delivered to our office.  As a result, there is a risk of contamination during this step.  This has resulted in outbreaks of serious eye infections in several cities.  We have not seen this in Tampa, but it is a potential risk during additional processing step.

Lucentis was designed as a smaller molecule to penetrate the retina better, and, to minimize the risk of side effects as whatever small amount goes from the eye into the systemic circulation is eliminated more quickly (cleared within a few days as compared to a few weeks with avastin).  Lucentis is manufactured under more strict purification conditions for injection inside the eye, as a result, inflammation is much less common.  Finally, there have been no reports of contamination as it comes directly from the manufacturer.

BOTTOM LINE: Both these drugs are quite effective and have resulted in spectacular results in previously untreatable, blinding retinal disease.  We prefer to use Lucentis if your insurance covers it because: (1) it is the drug that is specifically FDA approved for the eye, (2) it is prepared with more strict purification guidelines for use inside the eye, (3) it is not processed by a commercial pharmacy as it goes directly from the manufacturer to our office, and (4) the molecular design of lucentis theoretically has less risk of systemic side effects.  However, we also use Avastin in our practice if the patient’s insurance only covers Avastin or if the patient needs to pay out of pocket, as costs for Avastin are much less than those for Lucentis (the reasons why will be addressed in a future blog).