2/10/22, 11:49 AM
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`PIER data suggest a need for tailored injection schedule
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`September 01, 2006
`5 min read
`PIER data suggest a need for tailored injection schedule
`Patients could receive injections as needed rather than every quarter, according to one investigator.
`
`The schedule for injections of ranibizumab should be tailored to each patient based on clinical evaluation, according to an
`investigator involved in clinical trials of the drug for treatment of age-related macular degeneration.
`
`At the Retinal Physician Symposium in the Bahamas, David M. Brown, MD, FACS, presented year 1 results from the 2-year
`PIER (Phase 3b, Multi-Center, Randomized, Double-Masked, Sham Injection-Controlled Study of the Ecacy and Safety
`of Ranibizumab in Subjects with Subfoveal Choroidal Neovascularization with or without Classic CNV Secondary to AMD)
`trial. That study included 184 patients with predominantly classic, minimally classic or occult with no classic wet AMD.
`
`The PIER trial used a less frequent schedule of injections than two other phase 3 trials of Lucentis (ranibizumab,
`Genentech), the ANCHOR and MARINA trials, Dr. Brown said. In those two 2-year trials, subjects were randomly assigned
`to receive injections of Lucentis in 0.3 mg or 0.5 mg doses or control (sham injection in MARINA, photodynamic therapy
`in ANCHOR) once a month.
`
`“In MARINA and ANCHOR, the subjects received injections every month for 24 months,” Dr. Brown explained. “In the
`PIER study, they got three monthly shots and then mandatory quarterly injections, not based on whether they needed it or
`not.”
`
`Tailored treatment
`Investigators in the PIER trial used the reduced schedule of injections in hopes of getting the same results as the MARINA
`and ANCHOR studies, Dr. Brown said. Initially, results were similar to the other studies, but after the rst 3 monthly
`treatments the mean visual acuity in the ranibizumab-treated eyes returned to baseline, rather than improving further as
`it had in the other studies.
`
`“For the rst 3 months, it was just like MARINA,” Dr. Brown said. “We saw a nice visual acuity improvement. But then
`when we went to mandatory quarterly dosing, the average patient’s vision dropped back down to baseline. This shows
`that we cannot just mandatorily treat on a quarterly basis and maintain the visual gains seen with the rst three monthly
`injections.”
`
`Physicians’ options, Dr. Brown said, include following the MARINA and ANCHOR protocols and continuing to give
`monthly injections or “trying to come up with a rational treatment approach with decreased injections.”
`
`“What makes sense to me and many others,” he said, “is to treat with ranibizumab until we eliminate all signs of
`choroidal neovascular membrane leakage on optical coherence tomography and then re-treat as frequently as needed to
`maintain this ‘anatomic’ success. By tailoring our treatment to the retina’s anatomic response, I am hopeful that we can
`maintain the visual acuity gains that we get with the initial Lucentis dosing.”
`
`Trial outcomes
`According to Genentech ocials, after the three monthly injections, the group receiving 0.3 mg of ranibizumab
`demonstrated a mean increase of 2.9 letters on a visual acuity chart, and the group receiving 0.5 mg showed an increase of
`4.3 letters. The control group lost a mean of 8.7 letters at 3 months.
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`https://www.healio.com/news/ophthalmology/20120331/pier-data-suggest-a-need-for-tailored-injection-schedule
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`1/3
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`Samsung et al. v. Regeneron IPR2023-00884
`Regeneron Pharmaceuticals, Inc. Exhibit 2087 Page 1
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`2/10/22, 11:49 AM
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`PIER data suggest a need for tailored injection schedule
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`After the 5-, 8- and 11-month injections, the treated patients returned on average to baseline visual acuity, while subjects
`in the control group continued to experience visual loss, according to Genentech.
`
`These results have led investigators to think that automatic quarterly treatments may be less eective than more frequent
`dosing or tailored dosing, Dr. Brown said.
`
`“The only trial data available other than PIER (ie, ANCHOR and MARINA) had phenomenal results with monthly
`mandatory injections,” he said. “The expense and incremental risks of 12 intraocular injections per year could be
`diminished if any of these monthly injections could be eliminated without aecting visual gains. I am hopeful that a
`tailored approach can be done by following patients closely and monitoring them with OCT and other clinical tests.”
`
`An effective tool
`Dr. Brown said it was “a shock to a lot of people” that patients in the PIER study did not maintain the improvements that
`were seen in the MARINA and ANCHOR trials.
`
`“You can’t just do mandatory quarterly injections. We are going to have to follow the patients, I think, every 4 to 6 weeks
`by OCT [optical coherence tomography] and if there is evidence of uid then reinject,” he said.
`
`The best tool to help tailor treatment is OCT, Dr. Brown said.
`
`“Some people are still using uorescein angiography, but the majority of our response to treatment will be guided by
`OCT,” he said. “OCT shows you the anatomic response to the treatment.”
`
`The device acts as a high-resolution optical biopsy that can demonstrate the presence of subretinal uid, intraretinal uid
`or sub-RPE [retinal pigment epithelium] uid indicating active CNV leakage, Dr. Brown said.
`
`“I use the macular thickness map protocol on the Stratus OCT [Carl Zeiss Meditec], which has six high-resolution cross-
`sectional views of the macula spaced 30º apart,” he said. “I look at every scan, just like a radiologist looks at every image
`on an MRI. The automated foveal thickness measurement is almost always inaccurate in wet AMD. Just as a cardiologist
`doesn’t rely on the EKG automated diagnosis, I rely more on my interpretation of the individual images than the retinal
`thickness measurements generated by the machine.”
`
`Patient response
`Dr. Brown said that in practice, outside the clinical trial setting, patients with AMD who are candidates for Lucentis will
`likely be given three monthly injections and then will be monitored regularly with OCT after the 3-month treatment.
`
`“We’re going to have to get the retina at and then see how well people will respond visually,” he said. “OCT at least gives
`us an anatomic response to treatment. For the rst time, we nally have an anti-VEGF agent that eectively anatomically
`corrects the retina in most patients. If I can keep that retina anatomically correct, I am hopeful that the patient can
`maintain those visual acuity gains.”
`
`He continued, “If they don’t have any recurrent uid on OCT, then we won’t inject, but if they do, we will reinject. The
`question is, how many patients are going to need how much treatment, and will we be able to maintain visual acuity gains
`more analogous to ANCHOR and MARINA with this approach?”
`
`Dr. Brown estimated that the average patient might need six or seven treatments in the rst year and hopefully fewer
`treatments in subsequent years.
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`https://www.healio.com/news/ophthalmology/20120331/pier-data-suggest-a-need-for-tailored-injection-schedule
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`2/3
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`Samsung et al. v. Regeneron IPR2023-00884
`Regeneron Pharmaceuticals, Inc. Exhibit 2087 Page 2
`
`

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`2/10/22,11:49 AM
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`PIER data suggest a need for tailored injection schedule
`
`“We don’t know that, though,until we get further out in following patients whoarein thesetrials,” he said.
`
`“But to be honest, this is better for physicians because it makes you a doctor again,” he continued. “You haveto seeif
`your patient is responding or not, and you haveto tailor treatment to the way the patient is responding.”
`
`Read next
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`Monovision maystill be considered but be prepared for tradeoffs
`
`
`For moreinformation:
`
`David M. Brown, MD,FACS, can be reached at Methodist Hospital of Houston, Texas, Greater Houston Retina Research,
`
`6560 Fannin St., Suite 750, Houston, TX 77030; 713-524-3434; fax: 713-524-3220; e-mail:
`
`dmbmd@houstonretina.com; Web site: www.houstonretina.com. Dr. Brown is a paid consultant for Genentech,
`Eyetech, Alcon, Allergan and Novartis. He hasno direct financial interest in the products mentionedin this article.
`
`
`
`
`e Genentech Inc., maker of Lucentis, can be reached at 1 DNA Way, South San Francisco, CA 94080-4990; 650-225-
`
`1000; fax: 650-225-6000; Website: www.gene.com
`
`e Daniele Cruz is an OSN Staff Writer whocoversall aspects of ophthalmology.
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`https://www.healio.com/news/ophthalmology/20120331/pier-data-suggest-a-need-for-tailored-injection-schedule
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`3/3
`
`IPR2023-00884
`Samsung et al. v. Regeneron
`Regeneron Pharmaceuticals, Inc. Exhibit2087
`Page3
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