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Demographics and demand spur innovation in ophthalmology

As the economy rebounds and demand for eye care increases, ophthalmology stands on the threshold of a new era of innovation and growth, according to some observers. Recognizing new opportunities, venture capital firms are investing in small startup companies that develop innovative new drugs and devices.

In addition, the U.S. Food and Drug Administration has taken steps to improve and expedite the regulatory review process.

“There’s a triangle of the essence of growth, I call it, in ophthalmology,” Jim Mazzo, executive chairman and CEO of AcuFocus and an operating partner at Versant Ventures, said. “If you look at the patient population, anytime you look at any category for growth, you look at what the drivers are. Demographics tend to be one of the largest drivers of any category, anything from video games to ophthalmology.”

George O. Waring IV, MD

Development in the ophthalmic drug and device markets should be focused on treating the largest possible number of patients, according to George O. Waring IV, MD.

Image: George Woolston/Charleston Mercury

Unmet clinical needs and globalization complete the “triangle of growth,” Mazzo said.

“When I entered this industry 34 years ago, you really had secular markets,” he said. “Today, one of the greatest penetrations of phacoemulsification cataract surgery is in Vietnam. One of the greatest penetrations of LASIK is in Korea. Brazil [has] one of the greatest penetrations of cataract surgery.”

Ophthalmology is entering an unprecedented period of development, according to Eric D. Donnenfeld, MD, OSN Cornea/External Disease Board Member.

“Despite all of the concerns about the economy, the FDA and the future of medicine, I don’t think there has been a more vibrant time in startups and development of new technology in ophthalmology,” Donnenfeld said. “At the present time, there are a number of new innovations that are being developed that are extremely exciting. They include not only pharmacologics but also surgical devices.”

Richard A. Lewis, MD, OSN Glaucoma Board Member, said that an aging population and improved diagnostics have increased the demand for treatment of serious eye diseases; an increasing number of patients require eye care and more disease is being diagnosed.

“We certainly haven’t cured blindness. In fact, as our aging population continues to expand, we have more disease than ever,” Lewis said. “With newer diagnostic equipment, we’ve been able to hone in on some diseases, for example, macular degeneration, which kind of broadens the need for medical therapy.”

Development should be focused on treating the largest possible number of patients, according to George O. Waring IV, MD.

“In terms of opportunities for growth in the ophthalmic drug and device markets, whenever we’re speaking to startup companies or venture capital firms, we’re always advising them to look at opportunities to help a lot of people,” Waring said.

Barbara S. Fant, PharmD

Barbara S. Fant

Consultant Barbara S. Fant, PharmD, noted that ophthalmology leads all medical specialties in terms of innovation.

“I’ve worked in many different therapeutic disciplines, and I always say that ophthalmology is the most inventive discipline that I’ve ever worked in,” Fant said. “When they see a problem and they see an unmet clinical need, they design something that meets that clinical need.”

Growing demand and unmet needs

As baby boomers age, they develop conditions such as age-related macular degeneration, dry eye disease, glaucoma and presbyopia, Donnenfeld said.

“I think that the more demanding population that many ophthalmologists are seeing, the demographics of the increasingly aging baby boomer population, and the diseases associated with aging such as AMD, dry eye, glaucoma and cataract surgery are proving to be the perfect storm for patients who are demanding better outcomes,” he said.

The challenge is meeting the high expectations of Generation Y, Generation X and baby boomers, who lead more active lives than their predecessors, Mazzo said.

“Our eyes are being challenged across all three age groups,” he said. “You have demographics driving it. If you talk to people, one of the biggest issues they face is their vision. They tend to overlook some other things but never their vision.”

Waring shared a similar observation on patients’ high expectations.

“Patients are fighting aging changes. They’re not going down easy,” Waring said. “They want solutions to stay young.”

Presbyopia correction is a great opportunity for development and growth, Waring said.

“Presbyopia is a ubiquitous disorder. Everybody gets it,” he said. “Half of Asia is presbyopic right now, and there will be over 2 billion presbyopic patients by the year 2020. Multiply that by two eyes, and that’s a great opportunity to make a difference. When you think about those numbers, coupled with technologies in the pipeline, it’s really changing the way that we approach patients.”

Thanks to new diagnostic technologies and femtosecond lasers, Waring’s practice is moving toward making the surgical correction of presbyopia and lens-based refractive surgery (or dysfunctional lens replacement) a new subspecialty.

“We’re even thinking about starting one of the first fellowships in the surgical correction of presbyopia,” Waring said. “We’re not only working on the cornea, we’re working much more on the lens and we’re doing this with laser. We’re addressing the entire optical system. We can often do that with just one [strategy], and sometimes we’ll use two or more strategies to get the patients the best quality of vision long term.”

Waring noted that his practice is using advanced diagnostics objectively assess functional aspects of vision and to educate patients about the effect of their aging disorder.

“We are using all advanced diagnostics that basically take patients on a digital tour of their eye,” Waring said. “When you’re talking about visual acuity, 20/20 is great, but there’s so much more to it. It’s quality of vision, functional vision.”

Small companies drive innovation

In the past, innovation typically took place in large companies, Donnenfeld said.

Eric D. Donnenfeld, MD

Eric D. Donnenfeld

“Now, however, because of the risk associated with innovation because of delays in FDA approval and the pathways being more difficult, companies are not willing to spend large numbers of dollars on research,” he said. “They would rather have technology being developed by small startup companies and venture capital-funded companies that can assume risk and be a little bit more nimble because they’re smaller. Because the larger companies are doing less in-house research, it has created an extraordinary opportunity for these small startup companies to fill the void that has been left behind.”

Donnenfeld said that some companies are moving overseas to develop new technologies.

“Because of the difficulties of working in the United States, a lot of companies are going abroad to develop these new technologies, which lends itself toward these startup companies that may be a bit more nimble,” Donnenfeld said.

Large companies tend to focus more on the development of new technologies, while small companies concentrate on research, Mazzo said.

“What needs to be accomplished is to provide products through the [research],” he said. “These small, independent entities where I’m involved now at Versant actually do the [research].”

Mazzo said that smaller companies generally have a single focus, which results in a rapid pace of innovation.

“Either you execute or you’re out of business,” Mazzo said. “So, our innovation is coming from these entrepreneurial practitioners and individuals who identify an unmet need and then just have that zealous approach. In ophthalmology, it seems to be much more prevalent than in some of the other categories.”

Fant shared a similar observation about small companies having a single focus on one technology.

“The smaller companies, their focus is definitely on that single technology, or it may be a planned series of technologies based off the same platform,” Fant said. “You have to not only sell the company resources in terms of gaining funding for that, but you have to sell that technology and the value of that technology, from a market perspective as well as from a clinical perspective.”

Small companies focusing on research and large companies focusing on development enjoy a symbiotic relationship, Mazzo said.

Jim Mazzo

Jim Mazzo

“[If you] look at all of the products that these [large] companies have, I can tell you that a good majority of them go back to one small company started in a venture group and was then acquired and built upon: IntraLase, Visx, things of that nature,” he said. “They all started somewhere in a smaller environment and then were populated by the great breadth and depth of these large strategics. It’s that entrepreneurial attitude.”

Mazzo also noted a strong relationship between industry and practitioners.

“This is probably one of the few industries where I see industry and the practitioner base in very strong collaborative efforts and not antagonistic,” Mazzo said. “The practitioners are involved with the companies, and the companies are involved with the practitioners in advancing these technologies. … I would say that it’s primarily these small entrepreneurial entities driving ophthalmology forward.”

Streamlining regulatory review

Fant said that large and small companies need to understand the regulatory review process, a critical step in innovation.

“The startup companies that do it the best get their regulatory consultant involved and their regulatory strategy in place from the very beginning of the process and then let the regulatory process drive their development,” Fant said.

One challenge faced by small companies is negotiating the regulatory review process. A small company needs to have a global strategy with regard to regulatory review, she said.

“Is the U.S. the last entry into the marketplace? Are they going to obtain CE mark so that they can sell their products internationally in Europe and any of the other countries that accept CE mark? Are they going into China or Japan? The Asian strategy is different than the South American strategy and the Latin America strategy, etc.,” Fant said.

The Food and Drug Administration Safety and Innovation Act, signed into law on July 9, 2012, expanded the FDA’s authority and strengthened its ability to safeguard and advance public health by collecting user fees from device manufacturers submitting premarket approval and new device exemption applications.

The Medical Device User Fee Amendments of 2012, or MDUFA III, took effect on Oct. 1, 2012, and are scheduled to expire on Oct. 1, 2017. The amendments authorized the FDA to collect user fees over 5 years that will enable the FDA to hire more than 200 full-time-equivalent workers to expedite the review process.

In exchange for the fees, the FDA is committed to render decisions on approval within a specific timeframe.

MDUFA III is the product of more than 1 year of public input, negotiations with industry representatives, and discussions with patient and consumer representatives.

“In my experience working with a number of startup companies, I don’t think we’ve reached the optimal solution. I can’t say that I’m happy with the speed of innovation and the way that the process has improved,” Donnenfeld said. “But I will say that the approval process is better today than it was 2 or 3 years ago, and I think we’re moving in the right direction. The FDA, I do believe, is committed to meeting the performance goals that were designed within MDUFA III.”

Mazzo, who participated in MDUFA III negotiations as chairman of AdvaMed, said the initiative has strengthened the collaboration between industry and the FDA.

“I would say that this has been the best time that I have seen industry and the FDA work in a collaborative effort,” Mazzo said. “The reason is very clear objectives. When you don’t have clear objectives or clear milestones and you don’t have accountability on both sides, you then have a mixture of misunderstandings and nothing gets accomplished.”

In addition, the Center for Devices and Radiological Health’s 2014-2015 Strategic Priorities focus on strengthening the clinical trial enterprise; striking a balance between premarket and postmarket data collection; and providing excellent customer service, an FDA document said.

“The strategic initiatives are strengthening the clinical trial enterprise and increasing innovation in the U.S., where FDA has finally recognized that innovative technology and development is going offshore,” Fant said, “Their goal is to increase the number of first-time studies in the U.S. and ways to facilitate the development in the U.S.”

The FDA and ophthalmic societies have joined forces to streamline the review of ophthalmic devices. In March 2014, the Center for Devices and Radiological Health and American Academy of Ophthalmology held a workshop focusing on the development of appropriate study endpoints for premium IOLs. In February 2014, the FDA and American Glaucoma Society held a public workshop to address challenges in the assessment of implantable minimally invasive glaucoma devices, according to a report published in JAMA Ophthalmology. In 2011, the National Eye Institute and FDA held the first symposium on functional vision outcomes and how they are used in clinical trials for retinal prostheses.

Ongoing advances and challenges

Innovative products from small research-oriented companies run the gamut from analgesics and glaucoma drainage devices to diagnostic imaging systems, drug-eluting implants and stem cell technology.

“The technologies that I find extremely exciting now are some that have actually come to the FDA and been approved,” Donnenfeld said.

For example, the iStent (Glaukos) satisfies the need for glaucoma management without medications, and WaveTec’s intraoperative aberrometer improves refractive outcomes in cataract surgery, Donnenfeld said.

Omidria (phenylephrine and ketorolac injection, Omeros), which the FDA approved in May 2014, is indicated for use in cataract surgery or IOL replacement to maintain pupil size by preventing intraoperative miosis and to reduce postoperative pain.

“Sometimes innovation relies upon dramatic improvements in technology, and sometimes very simple ideas can really lend themselves to improved patient care,” Donnenfeld said. “[Omidria] is not high-tech, but it will be a great innovation for ophthalmologists.”

Lewis noted recent advances in refractive and astigmatic diagnostics.

“The way we’re diagnosing [astigmatism] now is far superior to what it was a couple of years ago,” he said. “We have a better appreciation for the front of the cornea and the back of the cornea. It’s like the chicken and egg argument. Which is coming first, the need for therapeutics or the need for diagnostics? One of them pushes the other one forward.”

Ongoing IOL development will be critical to refractive outcomes, Lewis said. Emerging technologies include toric multifocal lenses and extended depth of focus lenses.

“We have all these measurements we take for the length of the eye and the curvature, so there’s that area of breakthrough,” he said. “And then you have the actual calculation itself. What implant are we putting in there? Then, the next big endeavor is how we can modify the implant to make it better yet. We really haven’t pushed the envelope as much as I would have hoped on implants in the last 10 or 15 years.”

Overall, novel drug delivery methods are the frontier of ophthalmology, Lewis said.

“I think there’s a huge push for drug delivery and that’s going to tie in both drug and device,” he said. “The balance of power right now is how we administer and the concept of injecting drugs for retinal disease. Sooner or later, that’s going to end. We’re going to look back and say, ‘Can you imagine that we used to inject every 6 weeks?’ At some point we’re going to have something in the eye that’s going to deliver drugs for 3 to 6 to 12 months.”

Drug-eluting implants are of great interest to regulators and clinicians, Lewis said.

“There’s a lot of money currently being spent on these delivery systems. I think the FDA is onboard and excited to see it. Certainly, the clinician welcomes it,” he said. “It’ll solve the compliance and adherence problem. And I think the pharmaceutical companies will be excited because it gives them access to a portion of the eye they don’t have access to. So, it’s happening as we speak.”

Waring said that extended-release devices, nanotechnology, stem cell therapy and biomechanical alteration will revolutionize treatment.

“I think the paradigm is going to change. We’re going to have more flexibility with drugs to easily address patients’ needs more effectively and with less dosing. It’s much easier for the patient,” Waring said. – by Matt Hasson

References:

Agenda for developing novel endpoints for premium intraocular lenses (IOL) workshop. www.aao.org/meetings/upload/FDA_iol_workshop_agenda.pdf.
Breakout session discussion questions for the participants www.aao.org/meetings/upload/Breakout-Session-Discussion-Questions-for-the-Participants.pdf.
CDRH 2014-2015 Strategic Priorities. www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cdrh/cdrhvisionandmission/ucm384132.htm. Updated June 13, 2014.
Eydelman MB. JAMA Ophthalmol. 2014;doi:10.1001/jamaophthalmol.2014.2826.
Food and Drug Administration Safety and Innovation Act. www.fda.gov/regulatoryinformation/legislation/federalfooddrugandcosmeticactfdcact/significantamendmentstothefdcact/fdasia/ucm20027187.htm. Updated Aug. 20, 2014.
Haimovitch L, Lachman M. 2014 OIS@ASCRS Executive Report. ois.net/2014-oisascrs-executive-report/. Published July 15, 2014.
Medical Device User Fee Amendments 2012. www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/MDUFAIII/. Updated June 26, 2014.
OIS Podcast. ois.net/category/podcast/.
Varma R, et al. Invest Ophthalmol Vis Sci. 2010;doi:10.1167/iovs.10-5627.
Weinreb RN, et al. Invest Ophthalmol Vis Sci. 2011;doi:10.1167/iovs.11-7895.

For more information:

Eric D. Donnenfeld, MD, can be reached at Ophthalmic Consultants of Long Island, 2000 North Village Ave., Rockville Centre, NY 11570; 516-766-2519; email: ericdonnenfeld@gmail.com.
Barbara S. Fant, PharmD, can be reached at Clinical Research Consultants Inc., 3308 Jefferson Ave., Upper Level, Cincinnati, OH 45220; 513-961-8200; email: bsfant@crc-regulatory.com.
Richard A. Lewis, MD, can be reached at 1515 River Park Drive, Sacramento, CA 95815; 916-649-1515; email: rlewiseyemd@yahoo.com.
Jim Mazzo can be reached at AcuFocus Inc., 32 Discovery, Suite 200, Irvine, CA 92618; 949-585-9511; email: jmazzo@acufocus.com.
George O. Waring IV, MD, can be reached at Medical University of South Carolina Storm Eye Institute, 167 Ashley Ave., Charleston, SC 29425; 843-792-1414; email: georgewaringiv@gmail.com.

Disclosures: Donnenfeld is a consultant for AqueSys, Glaukos and WaveTec Vision. Fant has no relevant financial disclosures. Lewis is a consultant for Alcon, Allergan, AqueSys, Ivantis and Oculeve. Mazzo is an operating partner at Versant Ventures. Waring has no relevant financial disclosures.

POINTCOUNTER

How do you think the Physician Payment Sunshine Act will hinder innovation in ophthalmology?

POINT

It may limit physician-industry interaction

John A. Hovanesian, MD, FACS

John A. Hovanesian

The Physician Payment Sunshine Act will certainly limit our industry’s interest in working with physicians on new drugs and devices. In general, I favor transparency of the financial relationship between doctors and industry. Why should payments to doctors be a secret? Most companies are doing nothing unethical or illegal. But the act does create a great deal of paperwork and added cost to both government and industry for documenting payments that are made. Every $2 bagel that any industry representative buys any physician needs to be tracked and reported on the Centers for Medicare and Medicaid Services website.

It is difficult to imagine the monumental cost of government employees entering all these payments into the government’s system, and most drug and device companies providing the data have contracted with third-party firms to create the documentation at arm’s length. According to some of my industry colleagues, the new rule has more than doubled their cost in working with physicians. So, how do companies respond to this cost pressure? By limiting their interaction with physicians and consultants. Will this hinder innovation? Probably not, but it will certainly reduce the involvement of physicians, who provide an important voice of reason in the process of developing drugs and devices that will meaningfully improve the care of their patients.

John A. Hovanesian, MD, FACS, is OSN Cataract Surgery Section Editor. Disclosure: Hovanesian consults with a number of health care companies.

COUNTER

Reporting burden may limit academic exchange

Michael X. Repka, MD, MBA

Michael X. Repka

I am very much in favor of transparency in payments, whether it be Medicare claims payments, research dollars or consultancies. But the biggest caveat there is that they have to be properly presented and vetted and they have to include things that are important, not things that are trivial. The Sunshine Act includes too much that is trivial, such as reprints of academic articles. Some physicians can get them electronically, but others, if they get a reprint from a company, the company has to include the value of that reprint in its reporting for that person. Gifts of textbooks are reportable, as well as videos. That type of educational material is not reasonable to include.

The ultimate question is, will the reports be so reliable as to be trustworthy?

I think it is reasonable for the public to ask the question, “Are my doctor’s decisions impacted in ways that are not in my interest based on financial or other influences?” I think that happens uncommonly. I think the bill’s negatives far outweigh the benefits.

Michael X. Repka, MD, is medical director for governmental affairs, American Academy of Ophthalmology. Disclosure: Repka has no relevant financial disclosures.

As the economy rebounds and demand for eye care increases, ophthalmology stands on the threshold of a new era of innovation and growth, according to some observers. Recognizing new opportunities, venture capital firms are investing in small startup companies that develop innovative new drugs and devices.

In addition, the U.S. Food and Drug Administration has taken steps to improve and expedite the regulatory review process.

“There’s a triangle of the essence of growth, I call it, in ophthalmology,” Jim Mazzo, executive chairman and CEO of AcuFocus and an operating partner at Versant Ventures, said. “If you look at the patient population, anytime you look at any category for growth, you look at what the drivers are. Demographics tend to be one of the largest drivers of any category, anything from video games to ophthalmology.”

George O. Waring IV, MD

Development in the ophthalmic drug and device markets should be focused on treating the largest possible number of patients, according to George O. Waring IV, MD.

Image: George Woolston/Charleston Mercury

Unmet clinical needs and globalization complete the “triangle of growth,” Mazzo said.

“When I entered this industry 34 years ago, you really had secular markets,” he said. “Today, one of the greatest penetrations of phacoemulsification cataract surgery is in Vietnam. One of the greatest penetrations of LASIK is in Korea. Brazil [has] one of the greatest penetrations of cataract surgery.”

Ophthalmology is entering an unprecedented period of development, according to Eric D. Donnenfeld, MD, OSN Cornea/External Disease Board Member.

“Despite all of the concerns about the economy, the FDA and the future of medicine, I don’t think there has been a more vibrant time in startups and development of new technology in ophthalmology,” Donnenfeld said. “At the present time, there are a number of new innovations that are being developed that are extremely exciting. They include not only pharmacologics but also surgical devices.”

Richard A. Lewis, MD, OSN Glaucoma Board Member, said that an aging population and improved diagnostics have increased the demand for treatment of serious eye diseases; an increasing number of patients require eye care and more disease is being diagnosed.

“We certainly haven’t cured blindness. In fact, as our aging population continues to expand, we have more disease than ever,” Lewis said. “With newer diagnostic equipment, we’ve been able to hone in on some diseases, for example, macular degeneration, which kind of broadens the need for medical therapy.”

Development should be focused on treating the largest possible number of patients, according to George O. Waring IV, MD.

“In terms of opportunities for growth in the ophthalmic drug and device markets, whenever we’re speaking to startup companies or venture capital firms, we’re always advising them to look at opportunities to help a lot of people,” Waring said.

Barbara S. Fant, PharmD

Barbara S. Fant

Consultant Barbara S. Fant, PharmD, noted that ophthalmology leads all medical specialties in terms of innovation.

“I’ve worked in many different therapeutic disciplines, and I always say that ophthalmology is the most inventive discipline that I’ve ever worked in,” Fant said. “When they see a problem and they see an unmet clinical need, they design something that meets that clinical need.”

Growing demand and unmet needs

As baby boomers age, they develop conditions such as age-related macular degeneration, dry eye disease, glaucoma and presbyopia, Donnenfeld said.

“I think that the more demanding population that many ophthalmologists are seeing, the demographics of the increasingly aging baby boomer population, and the diseases associated with aging such as AMD, dry eye, glaucoma and cataract surgery are proving to be the perfect storm for patients who are demanding better outcomes,” he said.

The challenge is meeting the high expectations of Generation Y, Generation X and baby boomers, who lead more active lives than their predecessors, Mazzo said.

“Our eyes are being challenged across all three age groups,” he said. “You have demographics driving it. If you talk to people, one of the biggest issues they face is their vision. They tend to overlook some other things but never their vision.”

PAGE BREAK

Waring shared a similar observation on patients’ high expectations.

“Patients are fighting aging changes. They’re not going down easy,” Waring said. “They want solutions to stay young.”

Presbyopia correction is a great opportunity for development and growth, Waring said.

“Presbyopia is a ubiquitous disorder. Everybody gets it,” he said. “Half of Asia is presbyopic right now, and there will be over 2 billion presbyopic patients by the year 2020. Multiply that by two eyes, and that’s a great opportunity to make a difference. When you think about those numbers, coupled with technologies in the pipeline, it’s really changing the way that we approach patients.”

Thanks to new diagnostic technologies and femtosecond lasers, Waring’s practice is moving toward making the surgical correction of presbyopia and lens-based refractive surgery (or dysfunctional lens replacement) a new subspecialty.

“We’re even thinking about starting one of the first fellowships in the surgical correction of presbyopia,” Waring said. “We’re not only working on the cornea, we’re working much more on the lens and we’re doing this with laser. We’re addressing the entire optical system. We can often do that with just one [strategy], and sometimes we’ll use two or more strategies to get the patients the best quality of vision long term.”

Waring noted that his practice is using advanced diagnostics objectively assess functional aspects of vision and to educate patients about the effect of their aging disorder.

“We are using all advanced diagnostics that basically take patients on a digital tour of their eye,” Waring said. “When you’re talking about visual acuity, 20/20 is great, but there’s so much more to it. It’s quality of vision, functional vision.”

Small companies drive innovation

In the past, innovation typically took place in large companies, Donnenfeld said.

Eric D. Donnenfeld, MD

Eric D. Donnenfeld

“Now, however, because of the risk associated with innovation because of delays in FDA approval and the pathways being more difficult, companies are not willing to spend large numbers of dollars on research,” he said. “They would rather have technology being developed by small startup companies and venture capital-funded companies that can assume risk and be a little bit more nimble because they’re smaller. Because the larger companies are doing less in-house research, it has created an extraordinary opportunity for these small startup companies to fill the void that has been left behind.”

Donnenfeld said that some companies are moving overseas to develop new technologies.

“Because of the difficulties of working in the United States, a lot of companies are going abroad to develop these new technologies, which lends itself toward these startup companies that may be a bit more nimble,” Donnenfeld said.

Large companies tend to focus more on the development of new technologies, while small companies concentrate on research, Mazzo said.

“What needs to be accomplished is to provide products through the [research],” he said. “These small, independent entities where I’m involved now at Versant actually do the [research].”

Mazzo said that smaller companies generally have a single focus, which results in a rapid pace of innovation.

“Either you execute or you’re out of business,” Mazzo said. “So, our innovation is coming from these entrepreneurial practitioners and individuals who identify an unmet need and then just have that zealous approach. In ophthalmology, it seems to be much more prevalent than in some of the other categories.”

Fant shared a similar observation about small companies having a single focus on one technology.

“The smaller companies, their focus is definitely on that single technology, or it may be a planned series of technologies based off the same platform,” Fant said. “You have to not only sell the company resources in terms of gaining funding for that, but you have to sell that technology and the value of that technology, from a market perspective as well as from a clinical perspective.”

PAGE BREAK

Small companies focusing on research and large companies focusing on development enjoy a symbiotic relationship, Mazzo said.

Jim Mazzo

Jim Mazzo

“[If you] look at all of the products that these [large] companies have, I can tell you that a good majority of them go back to one small company started in a venture group and was then acquired and built upon: IntraLase, Visx, things of that nature,” he said. “They all started somewhere in a smaller environment and then were populated by the great breadth and depth of these large strategics. It’s that entrepreneurial attitude.”

Mazzo also noted a strong relationship between industry and practitioners.

“This is probably one of the few industries where I see industry and the practitioner base in very strong collaborative efforts and not antagonistic,” Mazzo said. “The practitioners are involved with the companies, and the companies are involved with the practitioners in advancing these technologies. … I would say that it’s primarily these small entrepreneurial entities driving ophthalmology forward.”

Streamlining regulatory review

Fant said that large and small companies need to understand the regulatory review process, a critical step in innovation.

“The startup companies that do it the best get their regulatory consultant involved and their regulatory strategy in place from the very beginning of the process and then let the regulatory process drive their development,” Fant said.

One challenge faced by small companies is negotiating the regulatory review process. A small company needs to have a global strategy with regard to regulatory review, she said.

“Is the U.S. the last entry into the marketplace? Are they going to obtain CE mark so that they can sell their products internationally in Europe and any of the other countries that accept CE mark? Are they going into China or Japan? The Asian strategy is different than the South American strategy and the Latin America strategy, etc.,” Fant said.

The Food and Drug Administration Safety and Innovation Act, signed into law on July 9, 2012, expanded the FDA’s authority and strengthened its ability to safeguard and advance public health by collecting user fees from device manufacturers submitting premarket approval and new device exemption applications.

The Medical Device User Fee Amendments of 2012, or MDUFA III, took effect on Oct. 1, 2012, and are scheduled to expire on Oct. 1, 2017. The amendments authorized the FDA to collect user fees over 5 years that will enable the FDA to hire more than 200 full-time-equivalent workers to expedite the review process.

In exchange for the fees, the FDA is committed to render decisions on approval within a specific timeframe.

MDUFA III is the product of more than 1 year of public input, negotiations with industry representatives, and discussions with patient and consumer representatives.

“In my experience working with a number of startup companies, I don’t think we’ve reached the optimal solution. I can’t say that I’m happy with the speed of innovation and the way that the process has improved,” Donnenfeld said. “But I will say that the approval process is better today than it was 2 or 3 years ago, and I think we’re moving in the right direction. The FDA, I do believe, is committed to meeting the performance goals that were designed within MDUFA III.”

Mazzo, who participated in MDUFA III negotiations as chairman of AdvaMed, said the initiative has strengthened the collaboration between industry and the FDA.

“I would say that this has been the best time that I have seen industry and the FDA work in a collaborative effort,” Mazzo said. “The reason is very clear objectives. When you don’t have clear objectives or clear milestones and you don’t have accountability on both sides, you then have a mixture of misunderstandings and nothing gets accomplished.”

PAGE BREAK

In addition, the Center for Devices and Radiological Health’s 2014-2015 Strategic Priorities focus on strengthening the clinical trial enterprise; striking a balance between premarket and postmarket data collection; and providing excellent customer service, an FDA document said.

“The strategic initiatives are strengthening the clinical trial enterprise and increasing innovation in the U.S., where FDA has finally recognized that innovative technology and development is going offshore,” Fant said, “Their goal is to increase the number of first-time studies in the U.S. and ways to facilitate the development in the U.S.”

The FDA and ophthalmic societies have joined forces to streamline the review of ophthalmic devices. In March 2014, the Center for Devices and Radiological Health and American Academy of Ophthalmology held a workshop focusing on the development of appropriate study endpoints for premium IOLs. In February 2014, the FDA and American Glaucoma Society held a public workshop to address challenges in the assessment of implantable minimally invasive glaucoma devices, according to a report published in JAMA Ophthalmology. In 2011, the National Eye Institute and FDA held the first symposium on functional vision outcomes and how they are used in clinical trials for retinal prostheses.

Ongoing advances and challenges

Innovative products from small research-oriented companies run the gamut from analgesics and glaucoma drainage devices to diagnostic imaging systems, drug-eluting implants and stem cell technology.

“The technologies that I find extremely exciting now are some that have actually come to the FDA and been approved,” Donnenfeld said.

For example, the iStent (Glaukos) satisfies the need for glaucoma management without medications, and WaveTec’s intraoperative aberrometer improves refractive outcomes in cataract surgery, Donnenfeld said.

Omidria (phenylephrine and ketorolac injection, Omeros), which the FDA approved in May 2014, is indicated for use in cataract surgery or IOL replacement to maintain pupil size by preventing intraoperative miosis and to reduce postoperative pain.

“Sometimes innovation relies upon dramatic improvements in technology, and sometimes very simple ideas can really lend themselves to improved patient care,” Donnenfeld said. “[Omidria] is not high-tech, but it will be a great innovation for ophthalmologists.”

Lewis noted recent advances in refractive and astigmatic diagnostics.

“The way we’re diagnosing [astigmatism] now is far superior to what it was a couple of years ago,” he said. “We have a better appreciation for the front of the cornea and the back of the cornea. It’s like the chicken and egg argument. Which is coming first, the need for therapeutics or the need for diagnostics? One of them pushes the other one forward.”

Ongoing IOL development will be critical to refractive outcomes, Lewis said. Emerging technologies include toric multifocal lenses and extended depth of focus lenses.

“We have all these measurements we take for the length of the eye and the curvature, so there’s that area of breakthrough,” he said. “And then you have the actual calculation itself. What implant are we putting in there? Then, the next big endeavor is how we can modify the implant to make it better yet. We really haven’t pushed the envelope as much as I would have hoped on implants in the last 10 or 15 years.”

Overall, novel drug delivery methods are the frontier of ophthalmology, Lewis said.

“I think there’s a huge push for drug delivery and that’s going to tie in both drug and device,” he said. “The balance of power right now is how we administer and the concept of injecting drugs for retinal disease. Sooner or later, that’s going to end. We’re going to look back and say, ‘Can you imagine that we used to inject every 6 weeks?’ At some point we’re going to have something in the eye that’s going to deliver drugs for 3 to 6 to 12 months.”

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Drug-eluting implants are of great interest to regulators and clinicians, Lewis said.

“There’s a lot of money currently being spent on these delivery systems. I think the FDA is onboard and excited to see it. Certainly, the clinician welcomes it,” he said. “It’ll solve the compliance and adherence problem. And I think the pharmaceutical companies will be excited because it gives them access to a portion of the eye they don’t have access to. So, it’s happening as we speak.”

Waring said that extended-release devices, nanotechnology, stem cell therapy and biomechanical alteration will revolutionize treatment.

“I think the paradigm is going to change. We’re going to have more flexibility with drugs to easily address patients’ needs more effectively and with less dosing. It’s much easier for the patient,” Waring said. – by Matt Hasson

References:

Agenda for developing novel endpoints for premium intraocular lenses (IOL) workshop. www.aao.org/meetings/upload/FDA_iol_workshop_agenda.pdf.
Breakout session discussion questions for the participants www.aao.org/meetings/upload/Breakout-Session-Discussion-Questions-for-the-Participants.pdf.
CDRH 2014-2015 Strategic Priorities. www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cdrh/cdrhvisionandmission/ucm384132.htm. Updated June 13, 2014.
Eydelman MB. JAMA Ophthalmol. 2014;doi:10.1001/jamaophthalmol.2014.2826.
Food and Drug Administration Safety and Innovation Act. www.fda.gov/regulatoryinformation/legislation/federalfooddrugandcosmeticactfdcact/significantamendmentstothefdcact/fdasia/ucm20027187.htm. Updated Aug. 20, 2014.
Haimovitch L, Lachman M. 2014 OIS@ASCRS Executive Report. ois.net/2014-oisascrs-executive-report/. Published July 15, 2014.
Medical Device User Fee Amendments 2012. www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/MDUFAIII/. Updated June 26, 2014.
OIS Podcast. ois.net/category/podcast/.
Varma R, et al. Invest Ophthalmol Vis Sci. 2010;doi:10.1167/iovs.10-5627.
Weinreb RN, et al. Invest Ophthalmol Vis Sci. 2011;doi:10.1167/iovs.11-7895.

For more information:

Eric D. Donnenfeld, MD, can be reached at Ophthalmic Consultants of Long Island, 2000 North Village Ave., Rockville Centre, NY 11570; 516-766-2519; email: ericdonnenfeld@gmail.com.
Barbara S. Fant, PharmD, can be reached at Clinical Research Consultants Inc., 3308 Jefferson Ave., Upper Level, Cincinnati, OH 45220; 513-961-8200; email: bsfant@crc-regulatory.com.
Richard A. Lewis, MD, can be reached at 1515 River Park Drive, Sacramento, CA 95815; 916-649-1515; email: rlewiseyemd@yahoo.com.
Jim Mazzo can be reached at AcuFocus Inc., 32 Discovery, Suite 200, Irvine, CA 92618; 949-585-9511; email: jmazzo@acufocus.com.
George O. Waring IV, MD, can be reached at Medical University of South Carolina Storm Eye Institute, 167 Ashley Ave., Charleston, SC 29425; 843-792-1414; email: georgewaringiv@gmail.com.

Disclosures: Donnenfeld is a consultant for AqueSys, Glaukos and WaveTec Vision. Fant has no relevant financial disclosures. Lewis is a consultant for Alcon, Allergan, AqueSys, Ivantis and Oculeve. Mazzo is an operating partner at Versant Ventures. Waring has no relevant financial disclosures.

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POINTCOUNTER

How do you think the Physician Payment Sunshine Act will hinder innovation in ophthalmology?

POINT

It may limit physician-industry interaction

John A. Hovanesian, MD, FACS

John A. Hovanesian

The Physician Payment Sunshine Act will certainly limit our industry’s interest in working with physicians on new drugs and devices. In general, I favor transparency of the financial relationship between doctors and industry. Why should payments to doctors be a secret? Most companies are doing nothing unethical or illegal. But the act does create a great deal of paperwork and added cost to both government and industry for documenting payments that are made. Every $2 bagel that any industry representative buys any physician needs to be tracked and reported on the Centers for Medicare and Medicaid Services website.

It is difficult to imagine the monumental cost of government employees entering all these payments into the government’s system, and most drug and device companies providing the data have contracted with third-party firms to create the documentation at arm’s length. According to some of my industry colleagues, the new rule has more than doubled their cost in working with physicians. So, how do companies respond to this cost pressure? By limiting their interaction with physicians and consultants. Will this hinder innovation? Probably not, but it will certainly reduce the involvement of physicians, who provide an important voice of reason in the process of developing drugs and devices that will meaningfully improve the care of their patients.

John A. Hovanesian, MD, FACS, is OSN Cataract Surgery Section Editor. Disclosure: Hovanesian consults with a number of health care companies.

COUNTER

Reporting burden may limit academic exchange

Michael X. Repka, MD, MBA

Michael X. Repka

I am very much in favor of transparency in payments, whether it be Medicare claims payments, research dollars or consultancies. But the biggest caveat there is that they have to be properly presented and vetted and they have to include things that are important, not things that are trivial. The Sunshine Act includes too much that is trivial, such as reprints of academic articles. Some physicians can get them electronically, but others, if they get a reprint from a company, the company has to include the value of that reprint in its reporting for that person. Gifts of textbooks are reportable, as well as videos. That type of educational material is not reasonable to include.

The ultimate question is, will the reports be so reliable as to be trustworthy?

I think it is reasonable for the public to ask the question, “Are my doctor’s decisions impacted in ways that are not in my interest based on financial or other influences?” I think that happens uncommonly. I think the bill’s negatives far outweigh the benefits.

Michael X. Repka, MD, is medical director for governmental affairs, American Academy of Ophthalmology. Disclosure: Repka has no relevant financial disclosures.