Regulatory burdens, rising costs hinder innovation in drug and device industries

A thriving partnership between academia and industry may help spur profitable and clinically beneficial research.

Increasing regulatory requirements, escalating research and development costs and other factors have significantly challenged pharmaceutical and device innovation during the last decade.

Academia and industry need to join forces to ensure productive research and timely drug approvals. Innovation needs to be built on enhanced insight into eye disease, Richard L. Lindstrom, MD, OSN Chief Medical Editor, said at the Ophthalmology Innovation Summit held before the American Academy of Ophthalmology meeting in San Francisco.

“The real core issue is continuing development of theory and understanding of the pathophysiology of the disease process,” Dr. Lindstrom said. “From my perspective, that really should drive research. It’s amazing how much research is done by industry, but much of it is also done in academia. We need to keep that partnership strong. We need to protect it, in my opinion, from attack from our friends in Washington, D.C.”

Dr. Lindstrom expressed optimism that ophthalmology research will increase in the next decade as investigators seek new treatments for prevalent eye diseases.

“I am starting to see some companies struggling and that makes me unhappy,” he said. “But … I do believe that ophthalmology may be a rare opportunity, even in the next decade, because of the number of opportunities they have that can significantly impact how our patients see.”

Diminishing returns

Dr. Lindstrom described an inverse relationship between research and development spending by the pharmaceutical industry and the number of new medication approvals granted over the last 10 years. In 1997, industry invested about $15 billion, resulting in more than 60 new medication approvals. In 2006, industry invested about $45 billion, generating fewer than 20 new medication approvals.

If the trend continues, $135 billion invested in 2016 would yield no drug approvals, Dr. Lindstrom said.

Research costs and the current length of the U.S. Food and Drug Administration approval process — 8 to 12 years — discourage research and investment, Dr. Lindstrom said.

In addition, on average only 8% of products currently in phase 1 clinical trials will ultimately receive FDA approval. The average non-capitalized cost of pre-market trials is $403 million per medication and $100 million per device. Currently, 446 ophthalmic medication studies are being conducted in the U.S. alone, which is positive, but investors are becoming much more selective in their new investments, he said.

“You do have to be objective about what you decide to invest in. Does it really have a chance to succeed? Is there going to be a big enough market?” Dr. Lindstrom said.

According to a 2008 member survey conducted by the Advanced Medical Technology Association (AdvaMed), the factor that most negatively affected the climate of innovation in medical technologies in recent years was FDA regulatory requirements (84%). Other leading factors were cost of clinical research (74.1%), Medicare coverage and reimbursement requirements (71.6%), research and development costs related to movement into new markets (66.7%), and U.S. private payer coverage and reimbursement requirements (63.9%).

Age-related eye disease

The baby boom generation, those who are age 45 to 63 years, numbers approximately 78 million people. The incidence of dry eye, blepharitis, cataract, glaucoma and age-related macular degeneration promises to increase dramatically as that cohort ages, Dr. Lindstrom said.

Currently, 3.2 million American adults undergo cataract surgery and 700,000 to 1.4 million adults undergo refractive surgery annually. Sixty-four percent of Americans wear glasses and 15% wear contact lenses. Also, more than 100 million adults are presbyopic, Dr. Lindstrom said.

As the baby boomers and successive generations age, ophthalmology needs new drugs and devices to prevent or treat ocular surface disease, cataract, presbyopia and glaucoma, he said.

“Ocular surface disease is ubiquitous in the elderly population,” Dr. Lindstrom said. “About 40% of patients we see in ophthalmology have ocular surface disease: dry eye, blepharitis, allergies. Significant growth in opportunity here is already meaningful.”

There is a need for more agents that enhance the production of natural tears in lieu of artificial tears, Dr. Lindstrom said.

In cases of blepharitis and allergy, new agents such as AzaSite (azithromycin ophthalmic solution 1%, Inspire Pharmaceuticals) and Tobradex (tobramycin and dexamethasone sterile ophthalmic suspension, Alcon) offer relief, but there is still room for more treatments, Dr. Lindstrom said.

“I think we’re running out of antibiotics,” he said. “I don’t know if we can find another fluoroquinolone that would actually be better.”

The future of ocular antibiotics lies in drug delivery systems that lengthen delivery time and enhance contact, and in antiseptic agents, Dr. Lindstrom said.

The treatment of presbyopia will continue to drive innovations in refractive surgery. For example, femtosecond lasers enable the creation of patterns in the cornea that treat myopia, hyperopia, astigmatism and presbyopia.

“It’s minimally invasive,” Dr. Lindstrom said. “Visual recovery is fast and it has an instant ‘wow’ factor.”

Advances in cataract and glaucoma

Femtosecond laser technology also promises to advance cataract surgery, Dr. Lindstrom said.

“We revolutionized LASIK surgery with the femtosecond laser, and I believe we’re about to revolutionize cataract surgery with the femtosecond laser as well,” he said.

For example, a femtosecond laser can make a perfect anterior capsulorrhexis that might enhance the performance of an accommodating IOL.

In glaucoma, companies such as Santen Pharmaceutical and Inspire are developing a Rho-kinase inhibitor that increases aqueous outflow by acting on trabecular meshwork cells. There is a need for a new category of glaucoma drugs, Dr. Lindstrom said.

Glaucoma patients should have a variety of treatment options, just as refractive patients may choose LASIK or corrective lenses, Dr. Lindstrom said. Most promising are minimally invasive glaucoma surgery devices.

“I want to be able to tell a patient who hates taking drops, can’t afford taking drops or who’s not compliant taking drops that I have a procedure that I can offer them as a reasonable alternative,” he said. – by Matt Hasson

• Richard L. Lindstrom, MD, can be reached at Minnesota Eye Consultants, 9801 DuPont Ave. S, Suite 200, Bloomington, MN 55431; 952-888-5800; fax: 952-567-6182; e-mail: rllindstrom@mneye.com.