Innovation in Retina

Samir Patel: A pioneer in anti-VEGF


Samir Patel: A Pioneer in Anti-VEGF

Jerry Helzner, Senior Editor
Edited by Emmett T. Cunningham Jr, MD, PhD, MPH, and Pravin U. Dugel, MD

Samir Patel, MD, president and CEO of Ophthotech, a developer of drugs for the treatment of retinal disease, felt so passionately about the potential of anti-VEGF drugs as an effective treatment for wet AMD that he left a secure and prestigious academic position at the University of Chicago in the late 1990s to pursue a high-risk venture as a principal in the biotech start-up Eyetech Pharmaceuticals.

“I did have to give up a lot of the patient contact that I enjoyed in the academic clinical setting, but at Eyetech I had the chance to work with anti-VEGF pioneers like Tony Adamis and others,” he says. “We all felt strongly that anti-VEGF was going to be a key to having success in treating wet AMD.”

Dr. Patel says the loss of patient interaction he experienced in leaving academic practice was offset by the opportunities offered in biotech to work with venture capitalists, create intellectual property and develop clinical trials.

“Much of what I did at Eyetech was new but it was also a continuum of the research I had been doing in the AMD space at the university,” he notes. “So I felt comfortable in making the transition.”


As the retinal community well knows, Eyetech was the developer of Macugen, the first anti-VEGF approved for the treatment of wet AMD. Macugen has the ability to stop or slow the progression of the disease in the majority of patients but was not able to improve visual acuity significantly. Thus, Macugen's moment in the spotlight proved to be relatively brief, as it was soon surpassed in efficacy by Lucentis, albeit with the need for repeated intravitreal injections.

“Macugen did represent an important step in not only advancing the treatment of wet AMD, but also in the validation of anti-VEGF as a key to treatment and in creating a great interest by venture capitalists in funding capital-intensive companies that develop drugs for retinal diseases,” asserts Dr. Patel. “So in those respects, Macugen has been very important.”


Today, Dr. Patel is exploring new ideas in drug development at Ophthotech, which is based in Princeton. One concept that has moved into a phase 2 clinical trial is a combination therapy that employs an anti-VEGF agent (Lucentis) with an anti-PDGF aptamer.

“A major limitation of the monotherapy anti-VEGF approach is lack of regression of the new vessels, which are responsible for the visual loss in wet AMD,” says Dr. Patel. “Therefore, a therapeutic regimen that induces neovascular regression would likely result in enhanced visual acuity for these patients. Ophthotech's anti-PDGF aptamer, E10030, targets PDGF, which regulates neovascular pericytes.”

Another Ophthotech initiative is a complement inhibitor that Dr. Patel believes could be effective against both the wet and dry forms of AMD. The company describes its anti-C5 aptamer, named ARC1905, as “a potent and selective inhibitor of factor C5 of the complement cascade.”

“We would love to develop the first successful therapy for dry AMD,” says Dr. Patel. “It's a great opportunity, given the large number of people we would be helping.”

Dr. Patel feels that the future of AMD treatment lies primarily in combination therapies.

“With monotherapy anti-VEGF treatment, two-thirds of the patients do not demonstrate substantial vision gains,” he notes. “We now have much greater knowledge of how angiogenesis progresses and we can see the value of combining therapies in a more effective manner.”

E10030 therapy results in stripping of neovascular pericytes from the CNV.


In addition to his focus on drug development, Dr. Patel also has a keen interest in the potential of more patient- and physician-friendly drug delivery systems.

“Our first thought is with the drug. Is it efficacious?” he asserts. “And in terms of the potential of any drug delivery system, it must not disrupt the efficacy of the drug. It's quite possible that we will find that we will need a range of different delivery systems for different types of drugs.”

Though both retina specialists and patients are eager to reduce the burden that intravitreal injections entail, Dr. Patel is quick to point out that intravitreal injections offer specific advantages that might be difficult to replicate in an alternative drug delivery format such as sustained release.

“Intravitreal injections have an attraction, which is primarily the simple, direct application to the site of the disease,” he notes. “Plus, intravitreal injections have proven to be relatively safe and they meet the requirement of not sacrificing the efficacy of the drug. However, given the treatment burden, there is no question: an elegant and effective drug delivery system would be a huge step forward.”


Dr. Patel says that the CATT study results were “pretty much in line with the general expectations” and shouldn't change usage patterns in the short term.

“What can change in the longer term is if the CATT results drive dramatic changes in reimbursement,” he says.

Dr. Patel does not see the CATT data as a government intervention with implications that could threaten future private investment in ophthalmic therapies.

“We are in a rapidly expanding field that is focused on developing therapies for unmet medical needs,” he says. “I don't believe the CATT study will discourage venture capital investment.”


Asked what advice he could offer to retina specialists who would like to become involved in entrepreneurship and innovation, Dr. Patel says the first requirement is to make sure any intellectual property you have developed is protected.

“There are no guarantees for innovators and the process involves quite a bit of risk,” he says. “But, certainly, as an innovator, you will get to interface with many interesting and talented people. The entire process is dynamic. If you have a passion for innovation, don't be deterred.” RP