Genentech (South San Francisco, Calif.), part of Roche (Basel, Switzerland), announced in January that Lucentis (ranibizumab injection) was approved by the Food and Drug Administration for the treatment of myopic choroidal neovascularization, a sight-threatening complication of high myopia. MCNV affects more than 41,000 people in the United States.1
Myopic choroidal neovascularization is a complication of high myopia (eyes with a refractive error of -6 D or greater, and/or axial length of 26.5 mm or more)1 in which the eye progressively lengthens from front to back and degenerates, and neovascularization develops. The condition is most prevalent in people ages 45 to 64.1
Until this approval for mCNV, the FDA-approved standard of care for mCNV has been verteporfin photodynamic therapy, although anti-VEGF injections were previously used off label and recommended as first-line treatments.2 Lucentis inhibits choroidal neovascularization by binding to and interfering with the vascular endothelial growth factor VEGF-A, the protein implicated in the formation of incompetent blood vessels.
The findings of the RADIANCE study form the basis of Genentech’s approval.3 This Phase III, 12-month, randomized, active-controlled study enrolled mCNV patients from 76 centers worldwide. They were randomized into three treatment groups: Group I received Lucentis 0.5 mg injection on day one, month one and thereafter as needed per visual acuity stabilization guidelines. Group II received Lucentis 0.5 mg injection on day one of the study and as needed thereafter per disease-activity criteria. Group III received vPDT on day one, but were permitted treatment with Lucentis and/or vPDT based upon disease activity, at investigators’ discretion, from months three through 11. Groups I and II showed dramatic gains in mean average best-corrected vision as measured by ETDRS letters through three months (10.5 and 10.6, respectively), compared to Group III (2.2 letters gained). Mean BCVA gains from baseline to month 12 were 13.8 letters for Group I: 14.4 for Group II; and, 9.3 for Group III, who were able to get Lucentis injections after three months. The results show that treatment with Lucentis on either schedule I or II resulted in dramatic early gains, and gains in BCVA continued throughout the study period. Group I patients received a median of four injections over 12 months; Groups II and III underwent a median of two. There were no adverse safety events.
“I think that having an FDA approval for Lucentis benefits patients and supports reimbursement from payers, as it is clearly superior to the other FDA-approved treatment, PDT,” says John A. Wells, III, MD, of the Palmetto Retina Center in West Columbia, S.C. “The RADIANCE study confirms my personal experience, and the collective experience of retina specialists, that PDT is vastly inferior to Lucentis 0.5 mg for the treatment of myopic CNV.” Dr. Wells adds that the upswing in ETDRS letters gained by the PDT group once Lucentis was allowed after three months is also important in illustrating “that PDT is not a good option for myopic CNV if anti-VEGF therapy is available.”
1. Willis JR, Vitale S, Morse L et al. The prevalence of myopic choroidal neovascularization in the United States. Ophthalmology 2016;123:8:1771-1782.
2. Adatia FA, Luong M, Munro M, Tufail A. The other CNVM: A review of myopic choroidal neovascularization treatment in the age of anti-vascular endothelial growth factor agents. Survey of Ophthalmol, 2015;60:3:204-15.
3. RADIANCE: A randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia. Ophthalmology 2014:121;3;682–692.
ReSTOR Toric MF: New Options And Challenges
As Alcon begins its scheduled first-quarter rollout of the new ReSTOR +3 D Multifocal Toric intraocular lens, which was approved in late December of 2016, surgeons are understandably interested in giving their patients a new alternative for vision correction post-cataract, but say it’s best to enter into the combined multifocal/toric world with eyes open, and to be prepared for new idiosyncrasies associated with getting the implantation right.
In the FDA study, at one year, the mean near acuity with the news lens was 20/25, and the mean binocular intermediate acuity at 60 cm was 20/25. Mean distance vision was 20/20. The lenses had rotated an average of around 2.5 degrees at the year mark. In terms of cylinder, at one year 75 percent of the first-implanted eyes were within 0.5 D of the preop target. Eighty percent of the second eyes were within 0.5 D of the target.
Alan Crandall, MD, director of glaucoma and cataract at the Moran Eye Center at the University of Utah, says being able to treat astigmatism adds a new dimension to the multifocal lens that patients respond to. “The increaased acuity, lack of glare and unwanted images—be they from straylight or halos—is really what most of our patients are excited about when you just correct their astigmatism with a toric lens,” he says. “But when they also have the ability to have distance and near vision, that’s a good combination. In the past, when working with multifocals where you had to try to do limbal relaxing incisions to correct the astigmatism, they were never as accurate as what you could get with a toric lens. Patients would come back and still say it wasn’t as sharp.”
But Dr. Crandall says these improved outcomes come at a price. “When you put these lenses in, you have to be right on target,” he avers. “I wouldn’t say it demands it, but you’re better off if you have a topography device that images both anterior and posterior corneal values. You also have to use multiple formulas–the Barrett, the ASCRS formula, the Olson—and then it helps to have something like ORA or Holos intraoperative aberrometry. I think this is why the penetration of toric lenses isn’t high: People are concerned about getting it properly on-axis.”
As for the best patient for the lens, Dr. Crandall says someone with extreme dry eye wouldn’t do well, nor would someone on medication for glaucoma because the lens will result in a little loss of contrast, which such a patient can’t afford. “Someone with pseudoexfoliation might not do well because the optics of the lens depend somewhat on the pupil,” he adds.
Trabodenoson Fails Phase III Trial for Glaucoma
On January 3, Inotek Pharmaceuticals Corporation (Lexington, Mass.), announced that its proposed glaucoma treatment, trabodenoson, failed its FDA phase III trial. Specifically, the drug didn’t achieve its primary endpoint of significantly reducing intraocular pressure compared to the placebo at every time point. Trabodenoson is designed to lower a patient’s IOP by altering the natural function of the trabecular meshwork.
The MATrX-1 Phase III trial was a randomized, double-masked, placebo-controlled trial, looking at 303 subjects diagnosed with primary open-angle glaucoma or ocular hypertension and an IOP greater than or equal to 24 mmHg and less than or equal to 34 mmHg. The trial lasted for three months. The subjects’ IOP was measured at four time points during the day: 8 a.m.; 10 a.m.; 12 p.m.; and 4 p.m. on days 14, 28, 42 and 84. The researchers administered three doses of trabodenoson: 3%/1,000 mcg once daily; 4.5%/1,500 mcg twice daily; and 6%/200 mcg once daily.
There were no significant safety or tolerability events reported in the study. The safety of trabodenoson was comparable to the placebo. Just four subjects (2.2 percent) discontinued the trial because of treatment-related adverse events.
The 6%/2,000 mcg dose of trabodenoson was superior to the placebo at days 84, 42, 14 and marginally superior at 28. Daily IOP reduction at three months for this dosage was 4.25 mmHg compared to the placebo’s 2.38 mmHg. This normal response confirms that the trial was properly conducted, Inotek says. However, the trial didn’t achieve its goal of significantly reducing IOP compared to the placebo at all time points. Researchers attribute this to a placebo response that was 2 to 3 mmHg greater than previously observed in their Phase II trial of the drug.
David Southwell, president and chief executive officer of Inotek, addressed the results in a conference call after the news broke. “Phase III results always contain unexpected elements, which teach us about the compounds we are developing,” he said. “We clearly need to better understand these results and, particularly, what drove the placebo response.”
However, Mr. Southwell remained optimistic. “Trabodenoson has identified itself as a drug with very clean safety profiles, with low side effects, both in the eye—such as hyperemia—and in the systemic compartment,” he said. “This trial, by some measure, showed an even better safety and tolerability profile than previously observed, particularly with hyperemia.” REVIEW