In 1994, we published an article entitled "How to Handle Acute Allergic Conjunctivitis" with an image of airborne pollens, a table listing available topical drugs, and even the author's head shot—all in a single page.
Needless to say, since those early days our ap-proach to covering complex clinical and surgical topics has become a bit more generous to our editorial contributors in terms of space. Fortunately, the contributor of that one-page allergy piece stayed with us through our evolution, and even helped define the changes along the way.
Dr. Mark Abelson has been with the Review since the beginning and we're proud to congratulate him on recently surpassing the 200 mark with his monthly column, Therapeutic Topics. An ophthalmologist by training and chairman and chief scientific officer of Ophthalmic Research Associates, Dr. Abelson has a unique perspective of more than 30 years on the evolution of the ophthalmic drug industry. In fact, Ora has participated in the development more than one-third of the ophthalmic drugs on the market today.
The two-century mark gave me an opportunity to talk with Dr. Abelson about where product development has been and where it's going. One of the surprising things you learn is that many of the challenges of the early days still remain.
"I think you'd have to call these years a period of evolution rather than revolution," says Dr. Abelson. "We still continue to search for the same things: a safe steroid; the antibiotic without resistance; the anti-allergic that has a great effect on all the signs, redness as well as swelling. We're still looking for a new glaucoma drug. Restasis was an improvement but not so much a breakthrough. The anti-VEGF drugs in retina are significant, but still only for a small percentage of patients."
Doubles and singles but no home runs. That's not to say things haven't changed for the better. Talk to Dr. Abelson about the current drug development landscape and positive signs abound.
"We're a mature specialty now," he says. "We no longer wait to repurpose a drug," from another therapeutic area.
A sign of that maturity is the presence of ophthalmology within the development process. "When I started out, for an ophthalmologist to be involved in pharmaceuticals was like being a leper," he says. There were no full-time ophthalmologists at the pharmaceutical companies. And back then, there were three ophthalmic pharmaceutical companies. That's it."
When I started out, for an ophthalmologist to be involved in ophthalmic pharmaceuticals was like being a leper... Now every start-up company has an ophthalmologist as a medical director. —Mark B. Abelson, MD
Owing to economic pressures, the drug development process itself has undergone a sea change. According to the
In response, throughout medicine a new type of product development collaboration has emerged. A sign of its presence in ophthalmology occurred before this year's AAO: the highly successful, second annual Ophthalmology Innovation Summit, which brings together venture capitalists, drug company executives and R&D experts, academics, physicians and regulatory specialists to share new ideas about emerging products and technologies in drug and device development. (Ora ran a similar program tailored to dry eye at this year's ARVO meeting.)
"Venture capital funding has revolutionized things, says Dr. Abelson. "The new paradigm is to get some funding, a venture capital board and a drug. And everything else is virtual and farmed out, so there's no setting up a duplicate lab and hiring all kinds of staff, which can burn time and funds. The financial people are getting more of their dollars spent at the bench and in the clinic than in the administrative component, so there are more dollars available."
And ophthalmology is well-positioned to take advantage, says Dr. Abelson. "The venture capitalists today are so bright. Many of them are MDs or ophthalmologists. One of the first is Gilbert Kliman. Others such as David Guyer and Les Kaplan, who ran Allergan's R&D for years, are in key advisory roles" for a host of start-ups, he says.
But improved tools have played an equally important role in making ophthalmic drug development a more efficient process, especially in the areas of dry eye and allergy. Ora has been at the forefront of innovation with such processes as the Conjunctival Allergen Challenge and the Ocular Surface Disease Index.
"Our interest has always been to improve the process," says Dr. Abelson. "Get the process right, at the clinical level—the challenges, the stress test, the endpoints—and then you move upstream and make sure that you're searching for compounds that act on worthwhile therapeutic targets. With things like high-throughput clinical models, one can screen rapidly with smaller numbers of patients, so you can do different dose-responses and look at different chemical entities within the same class more efficiently.
"As we have more precise ways of predicting in these areas, more drugs are going to come through. As you speed up the process, your hit rate is going to increase and the likelihood of a blockbuster is more reasonable."
Dr. Abelson believes a host of de-velopments have converged to make this a very promising time for ophthalmic drug development.
"The universities' job has always been to provide the background, the foundation, the proper targets," he says, "and I think that's alive and well. Mimetogen as a drug for dry eye, for example, came out of the work that Darlene Dartt [of Harvard and Schepens] did in identifying a receptor."
Despite the criticism of the agency overall, in ophthalmology, there are even reasons to view the FDA favorably. "We have Dr. Wiley Chambers at the FDA; he's an ophthalmologist," says Dr. Abelson. "Not all the divisions are run by people who understand the business as well as he does ophthalmology. I can't speak for other divisions, but in ophthalmology, the rest of the world looks to the FDA as a standard. We have very well-educated ophthalmologists and pharmacologists and regulatory people there who understand the business. You go and speak to people in other countries and it's just not the same level.
"So you have the regulatory process, the academic backup, the venture capital and a patent system that gives enough assurance that if you invest and your product works, at least you'll get enough of a runway to get a return on your investment.
"We have a system in place now that is running on all cylinders."
After 200 columns, we're happy to say that Dr. Abelson's column appears to be running on all cylinders as well. Says he, "There isn't a single column that I haven't learned something from." Me too.
