Advancements continue in development of retinal disease treatments
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An intravitreal injection is now the most common surgical procedure performed in the United States by an ophthalmologist.
In some countries, intravitreal injections are performed in a hospital-based surgery suite or ASC. In the U.S., the vast majority are performed in the office and often in an examining lane. Antisepsis with povidone-iodine is routinely utilized, but beyond that, injection techniques vary, with some using sterile gloves, a surgical mask and a speculum and others no gloves, no mask and simply holding the lids open manually. Many apply an antibiotic eye drop after the injection. There is discomfort during and after the injection, and the ocular surface and conjunctiva are stressed. Postoperative therapeutic regimens vary, but topical drops to reduce discomfort and inflammation and restore ocular surface health are commonly employed. The endophthalmitis rate is about one per 2,500 injections, half the national rate for endophthalmitis following cataract surgery. Another significant adverse event is transient and occasionally permanent IOP elevation. Pain, inflammation, secondary glaucoma, vitreous hemorrhage and nonresponse to treatment are potential adverse events.
It was interesting to me to learn that the typical patient who receives an intravitreal injection in the U.S. is 81 years old and more commonly a woman. The average presenting visual acuity is about 20/80, which means the patient can no longer drive in most states. After treatment, the patient with wet age-related macular degeneration on average improves three lines, which brings them to 20/50 and puts them back behind the wheel of their automobile, a big benefit for a senior patient. It usually takes three injections 1 month apart to induce a full therapeutic response, and then most U.S. surgeons switch to a treat-and-extend protocol requiring on average six injections a year. Unfortunately, despite a positive response and improved visual acuity, many patients discontinue treatment by 1 year after their first injection. Some of these patients are poor responders, but others simply cannot manage the logistics and cost of repeated office visits, while a few do not tolerate the discomfort or develop an adverse event. Improving durability, or the length of time between injections, is a significant target for new investment and could meaningfully reduce the burden on patients, providers and payers.
In regard to providers, nearly 4,000 of the 18,500 U.S. ophthalmologists are now performing the 8 million-plus intravitreal injections being done every year in the United States. If divided equally, this is 2,000 injections apiece per year, and many retina specialists perform more than 50 intravitreal injections in a single day. The majority of the ophthalmic surgeons who perform intravitreal injections are fellowship-trained retina specialists, but every year more comprehensive ophthalmologists add intravitreal injections to their offering. An intravitreal injection pays the doctor about $120, but rebates from the drug manufacturers increase the reimbursement to the physician’s practice significantly.
We now have many effective drugs for intravitreal injections. All of them originated in pioneering research in oncology, where it was found that certain tumors responded well to having their blood supply reduced by therapy with an anti-VEGF drug. The first anti-VEGF tested at Bascom Palmer Eye Institute by Philip J. Rosenfeld, MD, PhD, for retinal disease was Avastin (bevacizumab) from Genentech. His early findings were extraordinary and catalyzed creation of the largest new vertical ever experienced in ophthalmology.
There are significant differences in anti-VEGF cost. Using trade names, Avastin by Genentech, approved by the FDA in 2004 for cancer therapy (it is not FDA approved for use in the eye), is available for about $70 per injection whereas the Genentech follow-on product Lucentis (ranibizumab) is priced at $1,950 for 0.5 mg dose for wet age-related macular degeneration and retinal vein occlusion and $1,170 for 0.3 mg dose for diabetic macular edema. Its newest entry, Vabysmo (faricimab), is $2,190 per treatment. Eylea (aflibercept 2 mg) from Regeneron is priced at $1,418 and the newest member of the Regeneron family, Eylea HD (aflibercept 8 mg), is about $2,774 per injection. Beovu (brolucizumab) by Novartis is in the middle of the pack at $1,997.
Pharmaceutical product pricing in the U.S. is multifactorial and complex, but the new vertical of anti-VEGF injectable therapy for retinal disease is large and growing, encouraging further investment of human and financial capital.
The future will include better AI-supported home and office diagnostics, which will improve the patient journey and reduce patient and provider time burdens. Topical, subcutaneous, oral, subconjunctival, suprachoroidal and intravitreal treatments with new molecules that extend the time interval between injections are being developed. Especially promising at present are several tyrosine kinase inhibitors. Extended-release platforms, cell therapy and even gene therapy that can modify retinal or retinal pigment epithelium cells to become an anti-VEGF “biofactory” are all a part of our future.
The innovation cycle is alive and well-funded in this arena of therapy. The future advances will likely surprise and even amaze us to the benefit of patients, physicians and payers. A win-win-win.
Editor’s note: This article was updated on May 8, 2024, to clarify the FDA-approved use of Avastin and the prices of Lucentis and Vabysmo.
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