INNOVATION IN RETINA

A “Tipping Point” for Retina R&D: Implications and Expectations

PRAVIN U. DUGEL, MD ∙ EMMETT T. CUNNINGHAM, Jr., MD, PhD, MPH

As retinal physicians, we learn about new products at scientific meetings, in medical publications or via participation in clinical trials. These products have an entirely different side that we often don't see: the business side. Why should this matter? Why should we care?
The influence of industry in retina has never been more evident. We have formed an unplanned but fortuitous partnership with industry that has rapidly influenced the treatment of virtually every patient in our clinic. This almost accidental, newly forged partnership will continue to have an impact on daily practice for the foreseeable future. It is therefore imperative to understand retina and retinal products from a business perspective.
The goal of this new column is to introduce the readers to the men and women in industry who will help shape our world. We will study the development of drugs and devices; the risk and rewards of venture capitalism; and the world of product acquisition and development. In the end, we hope to give the readers a better understanding of our partners… and of our partnership.

In the opening pages of Malcolm Gladwell's incisive book, The Tipping Point, Gladwell describes the meteoric rise in popularity of Hush Puppies, the classic American brushed suede shoes with the lightweight crepe sole. He examines the seminal moment in 1996 when Hush Puppies won the prize for the best accessory at the Council of Fashion Designers awards dinner at Lincoln Center. Although most would point to this award as being the critical moment, Gladwell questions whether this was actually Hush Puppies' “tipping point.” Digging deeper, he concludes that the tipping point actually came when a few kids in the East Village and Soho started wearing the shoes precisely because no one else would wear them. He then traces how the fad spread to fashion designers and, eventually, to haute couture and the masses.

The field of retina has seen an equally meteoric rise in innovation in the last decade. Most would point to the introduction of Lucentis as that critical event. Some may even more precisely point to the ASRS meeting in Montreal in 2005, when the results of the ANCHOR and MARINA studies were announced, as this exact moment. It was, after all, the first time any of us witnessed a therapy of any type that actually reversed vision loss in patients with neovascular AMD (nAMD) — the leading cause of blindness in the developed world.

However, was this really our field's “tipping point”? As Gladwell dug deeper to find the tipping point for Hush Puppies, we, too, should dig deeper to find the tipping point for innovation in retina. A good argument can be made that the tipping point actually occurred in 2004 with the approval of Macugen, which validated VEGF as a target in nAMD and introduced most of the retina community to pharmacotherapy. Others might say the tipping point came five years earlier in, 1999, when PDT was first shown to slow vision loss in patients with nAMD.

For decades prior to 1999, therapeutic innovation in retina was slow and limited primarily to the findings of MPS and ETDRS and information from a few major academic centers or the National Eye Institute. New thoughts and ideas were few and far between. There was very little, if any, industry involvement in our field. The few companies that were involved in retina (eg, Alcon, Bausch+Lomb, Storz, Grieshaber), were device-oriented and involved almost exclusively in the surgical, not the medical, realm. The October 1999 issue of Archives of Ophthalmology represented the first time a major innovation in retina occurred with the sponsorship of a commercial entity, QLT. This changed everything. The doors were opened to the commercial opportunities in retina. Industry understood the tremendous unmet needs and, consequently, opportunities available.

It also understood that retina is a very closely knit, tight community, and that retina specialists are quick to embrace promising new technologies. Few commercial arenas offer the rapidity of adoption and the potential for return on investment seen in retina. The lessons of various companies that have realized and squandered opportunities, made and broken networking relationships, and initiated and floundered in clinical trials may one day provide a number of interesting case studies in business schools. Nonetheless, there is no denying that the very fabric of our field, retina, has been transformed. Nowhere is this more apparent than in the flow of innovation.

Prior to 1999, we certainly did have brilliant thinkers and doers in our field. To be sure, there were important in ventions, such as laser photocoagulation and vitrectomy sur gery. These inventions were usually a product of academicians who freely shared their ideas in meetings, and then practitioners in private practice adopted them. There were few venture capitalists, angel investors or patent lawyers interested in ophthalmology, let alone retina. Nevertheless, the introduction of PDT and the VEGF inhibitors may be considered monumental innovations. By the time information reached clinicians, an enormous amount of work had gone into establishing the scientific foundation and advancing treatments through randomized clinical trials of the sort required by the FDA.

This all required a huge financial investment, and risk. The investment in financial infrastructure, patent protection, marketing, etc., had already been made. A significant monetary risk had been taken and an equally significant return on investment was expected. Indeed, retina was no longer an exception, a bastion of academic inquiry, but had been em braced by corporate America, where products were investments and time was money. Inventions were now transformed into innovations.

In the last decade, there has been a shift of thinkers and doers from just a handful of major academic institutions to many institutions, and not only confined to academia, but also large private practices. In fact, the distinction has been blurred. Because time is money, most clinical trial recruitment actually occurs in large private practices. That is not to say that academic institutions are still not essential as a breeding ground for brilliant young minds. However, where those minds go to work may not only be in academia — it may be private practice, industry or even investing.

The flow of information has now changed from being purely a small arena of academics to a flow from academic laboratory-based research sponsored largely by the NEI, to early clinical trials performed mostly in private practices and funded by venture capitalists (VCs), to large companies that specialize in commercialization. Each entity has a critical and complementary role. Figure 1 illustrates the change in investment in the last decade. Obvious is a sharp in crease in R&D funding from VCs and large industry (as represented by Alcon). The fact that NEI funding has remained essentially flat for a number of years is alarming. Academic institutions and the NEI are the breeding ground for early innovation and, without adequate funding, we can expect the introduction of innovative products to slow.

Figure 1. Total R&D funds by sector: National Eye Institute (NEI), venture capital (VC) and Alcon. While Alcon is the largest dedicated ophthalmology company, and its annual R&D investment now exceeds that of the NEI, the total investment from all public companies involved in ophthalmic R&D is much larger.

The extent of the change in the fabric of retina and the opportunities that lie ahead was highlighted at the inaugural “Ophthalmology Innovation Summit” held in San Francisco prior to the AAO meeting last year. In fact, over 400 people from various fields attended the standing room only venue (see Figure 2). This meeting was so successful that a second such meeting is planned prior to the AAO in Chicago (www.ophthalmologysummit.com).

Figure 2. Delegate attendees by sector at 2009's Ophthalmology Innovation Summit in San Francisco.

So who attends these meetings? And what do they do? Malcolm Gladwell describes three different types of people necessary to create a “tipping point” — the Connec tors, the Mavens and the Salesmen. Gladwell writes, “In the end, Tipping Points are a reaffirmation of the potential for change and the power of intelligent action. Look at the world around you. It may seem like an immovable, im placable place. It is not. With the slightest push — in just the right place — it can be tipped.”

Indeed, our retina world has been tipped. The purpose of this new column is to meet the Connectors, Mavens and Salesmen in our world who have “tipped” us and now help influence and shape our field. We hope that, in the end, it will be a reaffirmation of how far we have come in the last decade and of the great future potential we have to improve the treatment of blinding retinal disorders. RP