Letter re: Statements about Omidria

Issue: March 10, 2016

To the Editor:

We agree with Dr. Ferguson (Letter to the Editor, Ocular Surgery News, Feb. 25, 2016) about the importance of controlling surgical costs; however, many of the statements regarding Omidria (phenylephrine/ketorolac 1%/0.3%) in his letter are incorrect. The erroneous statements on pricing and reimbursement were addressed by Dr. Gustafson in his response to Dr. Ferguson’s letter, and other inaccuracies were clarified by Dr. Lindstrom in the editor’s response. We focus here on Dr. Ferguson’s significant misstatements not addressed by Drs. Gustafson or Lindstrom. For each, a factual correction follows.

“Preventing intraoperative miosis is already met by the addition of epinephrine.”

Epinephrine is a mydriatic agent only — it does not prevent surgically induced miosis caused by the action of prostaglandins, released as a result of surgical trauma, on the iris sphincter muscle. NSAIDs, like ketorolac in Omidria, directly inhibit inflammation and prostaglandin-mediated miosis. In clinical trials, Omidria was nearly fourfold better than phenylephrine in preventing pupil diameters less than 6 mm. Recent case-controlled studies independently conducted by surgeons also showed that use of Omidria, compared to epinephrine, statistically significantly reduced use of pupil-expanding devices and complication rates.

“Omeros reports up to a 24% adverse reaction rate ... that are essentially nil with the use of epinephrine.”

The adverse reactions referenced by Dr. Ferguson are those in the FDA-approved labeling for Omidria and were derived from the placebo-controlled clinical trials. As required by FDA, even adverse events that are inherent in routine cataract surgery (eg, eye irritation) are reported. Dr. Ferguson fails to cite that the adverse reaction rates for Omidria are essentially the same as those for placebo. For Dr. Ferguson’s comparison to be accurate, use of epinephrine must effectively eliminate the adverse events seen with placebo, ie, those inherent in cataract surgery.

Epinephrine has been used “without complication in irrigation solutions for more than 30 years.”

Numerous complications, including corneal transplantation, have been reported with epinephrine. The only epinephrine FDA approved for addition to ophthalmic irrigation solution (a significant accreditation concern for ASCs and HOPDs) is Adrenalin. The only other drug approved by FDA for addition to ophthalmic irrigation is Omidria. The labeling for intraocular use of Adrenalin includes warnings and adverse events specific to this use of epinephrine. Compounded epinephrine is not FDA approved and carries accreditation risk; there have been numerous high-profile safety concerns with compounding pharmacies including those that compound ophthalmology products.

Omeros developed Omidria by taking phenylephrine and ketorolac and “simply compounded them and ran clinical studies.”

Dr. Ferguson’s mischaracterization of the drug development process is surprising. While both phenylephrine and ketorolac are known entities and Omeros developed Omidria efficiently, Omeros spent over $350 million during the 10-year development process, culminating in FDA approval. The proprietary combination of phenylephrine and ketorolac in Omidria requires specialized formulation and processing to create a solution that maintains potency, stability, pH and sterility over its 36-month shelf-life. FDA viewed Omidria as a new drug, requiring that Omeros conduct toxicology, pharmacokinetics, pharmacodynamics, dose-finding, chemistry and manufacturing programs in addition to the required phase 1, phase 2 full factorial and two pivotal phase 3 clinical trials evaluating safety and efficacy.

“A 6-mm standard is simply an arbitrary parameter used to ‘prove efficacy.’”

FDA’s Dr. Wiley Chambers, based on literature, required that Omeros use the 6-mm pupil-diameter threshold to analyze the Omidria data, determining it to be an important and clinically meaningful endpoint. Clearly, Dr. Chambers’ decision was not arbitrary.

“Postoperative ‘pain’ is essentially nonexistent in this cadre of patients.”

While this may reflect Dr. Ferguson’s perspective, it is inaccurate. A recent literature review found that up to 42% of cataract surgery patients experienced pain within the first 72 postoperative hours. The incidence of moderate-to-severe pain in the first postoperative hours was up to 35%. Any opportunity to improve patient comfort and satisfaction should be a welcome benefit.

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Dr. Ferguson begins his letter by stating that his perspective was characterized by Allison Shuren as “misguided” at the 2015 ACES/SEE meeting. At the 2016 ACES/SEE meeting, Dr. Ferguson’s colleague Dr. Gary Wörtz mentioned in a panel discussion that he does not understand the value proposition for Omidria. As demonstrated in the Omidria clinical trials and in those conducted independently by surgeons following commercialization, the drug’s value is clear — improved patient outcomes and multiple economic implications of having been granted pass-through status by CMS, as described by Drs. Gustafson and Lindstrom, together with broad commercial coverage and the OmidriAssure patient assistance programs. Potential cost savings with Omidria include reduced need for pupil-expanding devices, reduced need for compounded products, which are not separately reimbursed and carry liability and accreditation risks, shorter surgical times and substantial reduction in costs associated with diagnosing and managing complications that can be avoided when Omidria is used.

With these clarifications, we hope that Dr. Ferguson, his colleagues and OSN readers have a better appreciation of the value of Omidria to ophthalmic surgeons and their patients.

Medical Affairs, Omeros Corporation

References:
Guzek JP, et al. Ophthalmology. 1987;doi:10.1016/S0161-6420(87)33424-4.
Narendran N, et al. Eye (Lond). 2009;doi:10.1038/sj.eye.6703049.
Porela-Tiihonen S, et al. J Cataract Refract Surg. 2013;doi:10.1016/j.jcrs.2013.03.012.