In this MD Newsline exclusive interview with vitreoretinal specialist Dr. Murtaza Adam, we discuss treatment strategies for wet AMD and the latest research.
What is your treatment strategy for wet AMD and how is it tailored to each patient? How do these treatments work? How do you decide when to switch treatments?
Dr. Murtaza Adam:
“Current treatment for neovascular or wet AMD is primarily pharmacologic. The focus of the treatment is to stabilize or inhibit the leakage from neovascular membranes, aberrant blood vessels growing within and underneath the retina that can cause damage to macular cells.
Prior to the pharmacologic treatments we have today, we used to utilize laser treatments to cauterize those vessels. We found those treatments to be effective but destructive, with secondary damage to the macular tissue, and they had unwanted side effects of vision loss.
And so, these pharmacologic treatments are focused on stabilizing these blood vessels with an antibody or antibody fragment approach. These are biologics that we inject into the eye, and these biologics inhibit a family of vascular growth factors called vascular endothelial growth factors (VEGF). There are three major subtypes of VEGF that these drugs inhibit. Currently, we have four medicines on the market that slow the growth of and leakage from these vessels.
When it comes to individualizing treatment for each patient, we use a paradigm called ‘treat and extend.’ This paradigm is the one that’s most commonly used by vitreoretinal specialists. A patient is treated with an intraocular injection after being numbed and prepared with antibiotics, and the injection delivers these biologic medicines directly to the retina in the vitreous cavity. We start with monthly injections, and we watch the patient’s exam, imaging, and vision, looking for improvement over time.
As we start to normalize the anatomy and improve the vision, we then try to extend the time between the injections by a certain interval, usually by 2 weeks. And the longer and longer we go, we’ll find for some patients that we’ve gone too long, and they’ve gotten some recurrent vision loss because the effect of the medicine has worn off, so we tighten up the interval. On average, patients will make it every 6 or 8 weeks between treatments without having a recurrence or drop of vision.
There are some patients that we find that need to be treated every 4 weeks, while others can get away with being treated every 12 weeks. It’s very individualized care, and that way, we’re not undertreating, and we’re not overtreating. This approach really balances the need for efficacy and safety with treatment burden.”
Can your share with us your professional opinion of Beovu (brolucizumab) and if you use it with your patients?
Dr. Murtaza Adam:
“I should say I don’t use the drug as first-line. Brolucizumab or Beovu is the latest drug to be approved by the FDA for wet AMD. The unique design of the drug is that it has an extremely small molecular size, so that you can fit an extremely high dose in a small volume. With that high molar concentration, you can inhibit the activity of VEGF to a much higher degree than we previously could.
As retina specialists, we’ve been spoiled with a very low rate of inflammation as a side effect of treatment. Beovu, after its release, showed a rare but sometimes irreversible inflammatory event that could cause irreversible vision loss in patients. And so, there have been numerous investigations into the exact frequency and risk factors for the development of this rare complication.
In my practice, I use Beovu for my patients who are failing treatment with monthly injections of the other three currently available injectable drugs that we have for wet AMD. For me, that’s a very small percentage of patients. The drugs that we have work very well. For me, to take an extra risk in patients who are experiencing an adequate benefit from the drugs that we’re currently using—the risk-benefit’s [just] not there.
But there is a small handful of patients that I think could benefit and do benefit from Beovu. As we learn more about the risk factors and, perhaps, some biologic markers that we could pre-test patients for, there may be greater adoption of this medication by retina specialists. But we are highly biased towards something that’s safer over something that may be slightly more effective than what we have. And that’s where I think most retina specialists stand on Beovu.”
Which of the latest research studies on wet AMD are you most interested in regarding treatment safety and efficacy?
Dr. Murtaza Adam:
“In our practice of fourteen ophthalmologist subspecialists, including retina specialists, we run clinical trials all the way from phase 1 to phase 3. Being a part of cutting-edge wet AMD research is exciting and a privilege to participate in. I’m fortunate to have had exposure to a variety of treatments in the pipeline.
One of them that I’m really excited about is faricimab. Faricimab has been in development for many years and finally finished its phase 3 clinical trial. It’s the first bispecific molecule used for the treatment of wet AMD. All the molecules that we currently use to treat wet AMD are unispecific: they target a single protein in the eye. Faricimab targets two proteins in the eye: VEGF and ANG2. In combination, attacking two pathways, in theory, the drug is more effective.
An interesting thing about faricimab is that it can be used quarterly or slightly less than quarterly with the same efficacy as a drug that we use currently that’s used monthly. That’s a really exciting benefit for patients who have a high treatment burden, with family members taking them back and forth to their appointments. So instead of coming in 10 to 12 times a year, they might be able to get away with coming in 3 to 4 times a year for their maintenance treatments.
Another exciting technology is the port delivery system. It is a unique device. It’s about half the size of my pinky nail, if not a little bit smaller. It’s a silicone reservoir that’s like a gas tank. It can be implanted in the eye with a 30-minute procedure, and the device is filled with ranibizumab, which was the first FDA-approved anti-VEGF therapy for wet AMD. This medicine is slowly released by a titanium nanoparticle filter that allows the drug to be diffused into the vitreous cavity.
The amazing thing about this device is it can achieve efficacy equivalent to monthly injections of ranibizumab, with a refill rate of about every 6 months. That means you implant the device. It sits in the eye and secretes the drug at a controlled rate over 6 months. Then you refill the device in the office with a specialized refill needle, giving the patient another 6 months of continuous VEGF inhibition.
The last thing that I’m really excited about is gene therapy. There are two potential treatments for wet AMD in the pipeline. One is an injectable medication that’s injected into the vitreous cavity. The other is a drug that’s delivered with a surgical procedure called a vitrectomy. Both therapies involve adenovirus vectors that have genetic material that produces the biologic drugs that we inject in the eye.
So, basically, you trick the eye by infecting the eye with these modified adenoviruses. They insert this DNA material into the nuclei of the ocular cells, which then produce drugs like ranibizumab or aflibercept and inhibit VEGF in the long term. There’s some incredible phase 2 data showing patients that were getting injections 10 to 12 times a year, needing 0 injections after a year following a single treatment with this gene therapy. It could be curative.
So there are a lot of new treatments coming out for wet AMD. There are other exciting treatments that I didn’t even mention, but these are the critical ones for me.”
Responses have been condensed and lightly edited.