`
` NDA 21-756/S-018
`Page 3
`
`
`HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all of the information
`needed to use MACUGEN® safely and effectively. See full
`
`
`
`prescribing information for MACUGEN®.
`MACUGEN®(pegaptanib sodium injection)
`Intravitreal Injection
`Initial U.S. Approval: 2004
`
`
`------------------INDICATIONS AND USAGE------------------
`
`Macugen is indicated for the treatment of neovascular (wet)
`age-related macular degeneration (1).
`
`
`------------DOSAGE AND ADMINISTRATION-------------
`• FOR OPHTHALMIC INTRAVITREAL INJECTION
`
`ONLY (2.1).
`• Macugen 0.3 mg should be administered once every six
`
`
`
`
`weeks by intravitreous injection into the eye to be treated
`(2.2).
`
`
`
`
`
`
`
`•
`
`
`
`-------------WARNINGS AND PRECAUTIONS-------------
`• Endophthalmitis may occur following intravitreous
`
`
`
`injections. Proper aseptic injection technique should
`
`always be utilized when administering Macugen. Patients
`
`should be monitored during the week following the
`
`injection (5.1).
`
`
`
`Increases in intraocular pressure have been seen within 30
`minutes of injection of Macugen (5.2).
`• Rare cases of anaphylaxis/anaphylactoid reactions,
`
`including angioedema, have been reported in the post-
`marketing experience (5.3).
`
`
`
`
`
`8.3 Nursing Mothers
`
`
`8.4 Pediatric Use
`
`
`8.5 Geriatric Use
`10 OVERDOSAGE
`
`
`11 DESCRIPTION
`
`
`12 CLINICAL PHARMACOLOGY
`
`
`
`
`12.1Mechanism of Action
`
`
`12.3Pharmacokinetics
`13 NONCLINICAL TOXICOLOGY
`
`
`
`
`
`13.1Carcinogenesis, Mutagenesis, Impairment of Fertility
`
`
`13.2Animal Toxicology and/or Pharmacology
`
`14 CLINICAL STUDIES
`
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`
`17 PATIENT COUNSELING INFORMATION
`
`
`
`
`
`
`*Sections or subsections omitted from the full prescribing
`information are not listed.
`
`
`
`-----------DOSAGE FORMS AND STRENGTHS-----------
`•
`
`0.3 mg/90 µL solution in a single-use syringe for
`
`intravitreal injection (3).
`
`
`---------------------CONTRAINDICATIONS--------------------
`• Ocular or periocular infections (4.1).
`
`
`• Hypersensitivity (4.2).
`
`
`
`--------------------ADVERSE REACTIONS--------------------
`
`
`
`
`Most common adverse reactions (reported in 10-40% of
`
`patients treated with Macugen for up to two years) are
`anterior chamber inflammation, blurred vision, cataract,
`
`conjunctival hemorrhage, corneal edema, eye discharge, eye
`irritation, eye pain, hypertension, increased intraocular
`
`pressure (IOP), ocular discomfort, punctate keratitis, reduced
`
`visual acuity, visual disturbance, vitreous floaters, and
`vitreous opacities (6.2).
`
`To report SUSPECTED ADVERSE REACTIONS, contact
`
`Eyetech Inc. at 1-866-MACUGEN (1-866-622-8436) or
`FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
`
`
`
`See 17 for PATIENT COUNSELING INFORMATION
`
`
`Revised: 07/2011
`
`
`
`
`
`____________________________________________________________________________________________________________
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`1
`INDICATIONS AND USAGE
`
`
`
`2. DOSAGE AND ADMINISTRATION
`
`
`
`
`2.1 General Dosing Information
`
`
`2.2 Dosing
`
`
`2.3 Preparation for Administration
`
`
`2.4 Administration
`
`3 DOSAGE FORMS AND STRENGTHS
`
`
`4 CONTRAINDICATIONS
`
`
`
`
`
`4.1 Ocular or Periocular Infections
`
`
`4.2 Hypersensitivity
`5 WARNINGS AND PRECAUTIONS
`
`
`
`
`5.1 Endophthalmitis
`
`
`5.2 Increases in Intraocular Pressure
`
`
`5.3 Anaphylaxis
`6 ADVERSE REACTIONS
`
`
`
`
`6.1 Injection Procedure
`
`
`6.2 Clinical Studies Experience
`
`
`6.3 Postmarketing Experience
`8 USE IN SPECIFIC POPULATIONS
`
`
`
`
`8.1 Pregnancy
`
`
`
`Reference ID: 3026883
`
`Regeneron Exhibit 1191.001
`Regeneron v. Novartis
`IPR2021-00816
`
`
`
`
`
` NDA 21-756/S-018
`Page 4
`
`
`FULL PRESCRIBING INFORMATION
`
`1
`
`2.
`
`INDICATIONS AND USAGE
`Macugen is indicated for the treatment of neovascular (wet) age-related macular
`
`degeneration.
`
`
`DOSAGE AND ADMINISTRATION
`2.1 General Dosing Information
`FOR OPHTHALMIC INTRAVITREAL INJECTION ONLY.
`2.2 Dosing
`Macugen 0.3 mg should be administered once every six weeks by intravitreous injection into
`
`the eye to be treated.
`2.3 Preparation for Administration
`Macugen should be inspected visually for particulate matter and discoloration prior to
`
`administration. If visible particulates are observed and/or the liquid in the syringe is
`
`discolored, the syringe must not be used.
`
`Administration of the syringe contents involves assembly of the syringe with the
`
`administration needle. The injection procedure should be carried out under controlled aseptic
`conditions, which includes the use of sterile gloves, a sterile drape, and a sterile eyelid
`speculum (or equivalent). When ready to assemble syringe and administer injection,
`carefully peel open pouches, remove contents, and place on sterile field. If upon opening the
`pouch, the plastic clip is missing or not attached to the syringe, the syringe should not be
`used.
`To avoid compromising the sterility of the product, do not pull back on the plunger.
`1. Remove the syringe from the plastic clip.
`
`2. Twist off cap.
`
`3. Attach the sterile BD® 30G ½” Precision Glide® administration needle (included) to the
`
`
`syringe by screwing it into the syringe tip.
`
`--Another sterile BD® 30G ½” Precision Glide® administration needle may be used in lieu of
`
`the one included. Remove the plastic needle shield from the needle.
`
`4. Holding the syringe with the needle pointing up, check the syringe for bubbles. If there
`
`are bubbles, gently tap the syringe with your finger until the bubbles rise to the top of the
`
`syringe. SLOWLY depress the plunger to eliminate all the bubbles and to expel the excess
`
`drug so that the top edge of the 3rd rib on the plunger stopper aligns with the pre
`printed black dosing line (See Figure 2, below).
`
`
`5. Inject the entire contents of the syringe.
`
`
`PRIOR to Injection
`
`Figure1. Before expelling air bubble and excess drug
`
`
`
`
`Reference ID: 3026883
`
`Regeneron Exhibit 1191.002
`Regeneron v. Novartis
`IPR2021-00816
`
`
`
`
`
` NDA 21-756/S-018
`Page 5
`
`
`
` READY for Injection
`
`Figure 2. After expelling air bubble and excess drug
`
`
`
`
`
`
`2.4 Administration
`The injection procedure should be carried out under controlled aseptic conditions, which
`includes the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or
`equivalent). Adequate anesthesia and a broad-spectrum microbicide should be given prior to
`
` the injection.
`The patient’s medical history for hypersensitivity reactions should be evaluated prior to
`performing the intravitreal procedure [see Warnings and Precautions (5) and Adverse Events
`(6)].
`Following the injection, patients should be monitored for elevation in intraocular pressure
`and for endophthalmitis. Monitoring may consist of a check for perfusion of the optic nerve
`head immediately after the injection, tonometry within 30 minutes following the injection,
`
`and monitoring during the week following the injection. Patients should be instructed to
`report any symptoms suggestive of endophthalmitis without delay.
`No special dosage modification is required for any of the populations that have been studied
`(i.e. gender, elderly).
`The safety and efficacy of Macugen therapy administered to both eyes concurrently have not
`
`been studied.
`
`
`
`Reference ID: 3026883
`
`Regeneron Exhibit 1191.003
`Regeneron v. Novartis
`IPR2021-00816
`
`
`
`
`
` NDA 21-756/S-018
`Page 6
`
`
`3
`
`DOSAGE FORMS AND STRENGTHS
`Single-use glass syringe pre-filled with 0.3 mg of Macugen® in a nominal 90 µL solution for
`intravitreal injection.
`
`CONTRAINDICATIONS
`4.1 Ocular or Periocular Infections
`Macugen is contraindicated in patients with ocular or periocular infections.
`4.2 Hypersensitivity
`Macugen is contraindicated in patients with known hypersensitivity to pegaptanib sodium or
`
`
`any other excipient in this product.
`
`WARNINGS AND PRECAUTIONS
`
`5.1 Endophthalmitis
`Intravitreous injections, including those with Macugen, have been associated with
`
`endophthalmitis. Proper aseptic injection technique should always be utilized when
`administering Macugen. In addition, patients should be monitored during the week following
`the injection to permit early treatment, should an infection occur [see Dosage and
`Administration (2.4)].
`5.2
`Increases in Intraocular Pressure
`Increases in intraocular pressure have been seen within 30 minutes of injection with
`Macugen. Therefore, intraocular pressure as well as the perfusion of the optic nerve head
`should be monitored and managed appropriately [see Dosage and Administration (2.4)].
`5.3 Anaphylaxis
`Rare cases of anaphylaxis/anaphylactoid reactions, including angioedema, have been
`reported in the post-marketing experience following the Macugen intravitreal administration
`procedure [see Adverse Events (6.3) and Dosage and Administration (2.4)].
`
`ADVERSE REACTIONS
`6.1
`Injection Procedure
`Serious adverse events related to the injection procedure occurring in < 1% of intravitreous
`
`included endophthalmitis [see Warnings and Precautions (5.1)], retinal
`injections
`detachment, and iatrogenic traumatic cataract.
`6.2 Clinical Studies Experience
`
`
`The most frequently reported adverse events in patients treated with Macugen 0.3 mg for up
`to two years were anterior chamber inflammation, blurred vision, cataract, conjunctival
`hemorrhage, corneal edema, eye discharge, eye irritation, eye pain, hypertension, increased
`intraocular pressure (IOP), ocular discomfort, punctate keratitis, reduced visual acuity, visual
`disturbance, vitreous floaters, and vitreous opacities.
` These events occurred
`in
`approximately 10-40% of patients.
`The following events were reported in 6-10% of patients receiving Macugen 0.3 mg therapy:
`Ocular: blepharitis, conjunctivitis, photopsia, vitreous disorder.
`Non-Ocular: bronchitis, diarrhea, dizziness, headache, nausea, urinary tract infection.
`
`
`4
`
`5
`
`6
`
`
`
`Reference ID: 3026883
`
`Regeneron Exhibit 1191.004
`Regeneron v. Novartis
`IPR2021-00816
`
`
`
`
`
` NDA 21-756/S-018
`Page 7
`
`
`
`The following events were reported in 1-5% of patients receiving Macugen 0.3 mg therapy:
`
`Ocular: allergic conjunctivitis, conjunctival edema, corneal abrasion, corneal deposits,
`
`
`corneal epithelium disorder, endophthalmitis, eye inflammation, eye swelling, eyelid
`
`
`retinal edema, vitreous
`irritation, meibomianitis, mydriasis, periorbital hematoma,
`hemorrhage.
`
`Non-Ocular: arthritis, bone spur, carotid artery occlusion, cerebrovascular accident, chest
`
`pain, contact dermatitis, contusion, diabetes mellitus, dyspepsia, hearing loss, pleural
`
`effusion, transient ischemic attack, urinary retention, vertigo, vomiting.
`
`
`6.3 Postmarketing Experience
`Anaphylaxis/anaphylactoid reactions, including angioedema, have been identified during
`postapproval use of Macugen. Because these reactions are reported voluntarily from a
`population of uncertain size, it is not always possible to reliably estimate their frequency or
`establish a causal relationship to drug exposure [see Warnings and Precautions (5.3) and
`
`Dosage and Administration (2.4)].
`
`8
`
`USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`Teratogenic Effects: Pregnancy Category B. Pegaptanib produced no maternal toxicity and
`no evidence of teratogenicity or fetal mortality in mice at intravenous doses of up to 40
`mg/kg/day (about 7,000 times the recommended human monocular ophthalmic dose of 0.3
`mg/eye). Pegaptanib crosses the placenta in mice.
`There are, however, no adequate and well-controlled studies in pregnant women. Because
`animal reproduction studies are not always predictive of human response, this drug should be
`used during pregnancy only if clearly needed.
`8.3 Nursing Mothers
`It is not known whether pegaptanib is excreted in human milk. Because many drugs are
`excreted in human milk, caution should be exercised when Macugen is administered to a
`nursing woman.
`8.4 Pediatric Use
`Safety and effectiveness of Macugen in pediatric patients have not been established.
`8.5 Geriatric Use
`Approximately 94% (834/892) of the patients treated with Macugen were ≥ 65 years of age
`and approximately 62% (553/892) were ≥ 75 years of age. No difference in treatment effect
`or systemic exposure was seen with increasing age.
`
`10
`
`OVERDOSAGE
`Doses of Macugen up to 10 times the recommended dosage of 0.3 mg have been studied. No
`additional adverse events have been noted but there is decreased efficacy with doses above 1
`mg.
`
`
`
`Reference ID: 3026883
`
`Regeneron Exhibit 1191.005
`Regeneron v. Novartis
`IPR2021-00816
`
`
`
`
`
`
`
` NDA 21-756/S-018
`Page 8
`
`
`11
`
`DESCRIPTION
`Macugen (pegaptanib sodium injection) is a sterile, aqueous solution containing pegaptanib
`sodium for intravitreous injection. Macugen is supplied in a single-dose, pre-filled syringe
`and is formulated as a 3.47 mg/mL solution, measured as the free acid form of the
`oligonucleotide. The active ingredient is 0.3 mg of the free acid form of the oligonucleotide
`without polyethylene glycol, in a nominal volume of 90 µL. This dose is equivalent to 1.6
`mg of pegaptanib sodium (pegylated oligonucleotide) or 0.32 mg when expressed as the
`sodium salt form of the oligonucleotide moiety. The product is a sterile, clear, preservative-
`free solution containing sodium chloride, monobasic sodium phosphate monohydrate, dibasic
`
`sodium phosphate heptahydrate, hydrochloric acid, and/or sodium hydroxide to adjust the pH
`and water for injection.
`Pegaptanib sodium is a covalent conjugate of an oligonucleotide of twenty-eight nucleotides
`in length that terminates in a pentylamino linker, to which two 20-kilodalton monomethoxy
`
`polyethylene glycol (PEG) units are covalently attached via the two amino groups on a lysine
`residue.
`Pegaptanib sodium is represented by the following structural formula:
`
`Where R is
`
`
`and n is approximately 450.
`
`
`
`Reference ID: 3026883
`
`
`
`Regeneron Exhibit 1191.006
`Regeneron v. Novartis
`IPR2021-00816
`
`
`
`
`
` NDA 21-756/S-018
`Page 9
`
`
`
` The chemical name for pegaptanib sodium is as follows: RNA, ((2'-deoxy-2'-fluoro)C-Gm-
`
`Gm-A-A-(2'-deoxy-2'-fluoro)U-(2'-deoxy-2'-fluoro)C-Am-Gm-(2'-deoxy-2'-fluoro)U-Gm-Am
`Am-(2'-deoxy-2'-fluoro)U-Gm-(2'-deoxy-2'-fluoro)C-(2'-deoxy-2'-fluoro)U-(2'-deoxy-2'
`fluoro)U-Am-(2'-deoxy-2'-fluoro)U-Am-(2'-deoxy-2'-fluoro)C-Am-(2'-deoxy-2'-fluoro)U-(2'
`deoxy-2'-fluoro)C-(2'-deoxy-2'-fluoro)C-Gm-(3'→3')-dT), 5'-ester with α,α'-[4,12-dioxo-6
`[[[5-(phosphoonoxy)pentyl]amino]
`carbonyl]-3,13-dioxa-5,11-diaza-1,15
`pentadecanediyl]bis[ω-methoxypoly(oxy-1,2-ethanediyl)], sodium salt.
`The molecular formula for pegaptanib sodium is C294H342F13N107Na28O188P28[C2H4O]n
`
`(where n is approximately 900) and the molecular weight is approximately 50 kilodaltons.
`Macugen is formulated to have an osmolality of 280-360 mOsm/Kg, and a pH of 6–7.
`
`
`
` CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`Pegaptanib is a selective vascular endothelial growth factor (VEGF) antagonist. VEGF is a
`
` secreted protein that selectively binds and activates its receptors located primarily on the
`surface of vascular endothelial cells. VEGF induces angiogenesis, and increases vascular
`permeability and inflammation, all of which are thought to contribute to the progression of
`the neovascular (wet) form of age-related macular degeneration (AMD), a leading cause of
`blindness. VEGF has been implicated in blood retinal barrier breakdown and pathological
`ocular neovascularization.
`Pegaptanib is an aptamer, a pegylated modified oligonucleotide, which adopts a three-
`
`dimensional conformation that enables it to bind to extracellular VEGF. Under in vitro
`
`testing conditions, pegaptanib binds to the major pathological VEGF isoform, extracellular
`VEGF165, thereby inhibiting VEGF165 binding to its VEGF receptors. The inhibition of
`
`VEGF164, the rodent counterpart of human VEGF165, was effective at suppressing
`pathological neovascularization.
`
`12.3 Pharmacokinetics
`
`Absorption
`In animals, pegaptanib is slowly absorbed into the systemic circulation from the eye after
`
`intravitreous administration. The rate of absorption from the eye is the rate limiting step in
`the disposition of pegaptanib in animals and is likely to be the rate limiting step in humans.
`In humans, a mean maximum plasma concentration of about 80 ng/mL occurs within 1 to 4
`days after a 3 mg monocular dose (10 times the recommended dose). The mean area under
`the plasma concentration-time curve (AUC) is about 25 µg·hr/mL at this dose.
`Pegaptanib is metabolized by nucleases and is generally not affected by the cytochrome P450
`system.
`Two early clinical studies conducted in patients who received Macugen alone and in
`combination with photodynamic therapy (PDT) revealed no apparent difference in the
`plasma pharmacokinetics of pegaptanib.
`
`
`Distribution/Metabolism/Excretion
`
`12
`
`
`
`
`
`Reference ID: 3026883
`
`Regeneron Exhibit 1191.007
`Regeneron v. Novartis
`IPR2021-00816
`
`
`
`
`
` NDA 21-756/S-018
`Page 10
`
`
`
`Twenty-four hours after intravitreous administration of a radiolabeled dose of pegaptanib to
`both eyes of rabbits, radioactivity was mainly distributed in vitreous fluid, retina, and
`aqueous fluid. After intravitreous and intravenous administrations of radiolabeled
`pegaptanib to rabbits, the highest concentrations of radioactivity (excluding the eye for the
`intravitreous dose) were obtained in the kidney. In rabbits, the component nucleotide, 2’
`
`fluorouridine is found in plasma and urine after single radiolabeled pegaptanib intravenous
`
`and intravitreous doses. In rabbits, pegaptanib is eliminated as parent drug and metabolites
`primarily in the urine.
`Based on preclinical data, pegaptanib is metabolized by endo- and exonucleases.
`In humans, after a 3 mg monocular dose (10 times the recommended dose), the average (±
`
`standard deviation) apparent plasma half-life of pegaptanib is 10 (±4) days.
`Special Populations
`
`Plasma concentrations do not appear to be affected by age or gender, but have not been
`studied in patients under the age of 50.
`
`13
`
`14
`
`NONCLINICAL TOXICOLOGY
`
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`Carcinogenicity studies with pegaptanib have not been conducted. No data are available to
`evaluate male or female mating or fertility indices.
`13.2 Animal Toxicology and/or Pharmacology
`Pegaptanib and its monomer component nucleotides (2’-MA, 2’-MG, 2’-FU, 2’-FC) were
`evaluated for genotoxicity in a battery of in vitro and in vivo assay systems. Pegaptanib, 2’
`O-methyladenosine (2’-MA), and 2’-O-methylguanosine (2’-MG) were negative in all assay
`(2’-FC) were
`systems evaluated.
`2’-fluorouridine
`(2’-FU) and 2’-fluorocytidine
`
`
`nonclastogenic and were negative in all S. typhimurium tester strains, but produced a non-
`dose related increase in revertant frequency in a single E. coli tester strain. Pegaptanib, 2’
`
`FU, and 2’-FC tested negative in cell transformation assays.
`
`CLINICAL STUDIES
`Macugen was studied in two controlled, double-masked, and identically designed
`randomized studies in patients with neovascular AMD. Patients were randomized to receive
`
`control (sham treatment) or 0.3 mg, 1 mg or 3 mg Macugen administered as intravitreous
`
`injections every 6 weeks for 48 weeks. A total of approximately 1200 patients were enrolled
`with 892 patients receiving Macugen and 298 receiving a sham injection. The median age of
`the patients was 77 years. Patients received a mean 8.5 treatments out of a possible 9 total
`treatments across all treatment arms. Patients were re-randomized between treatment and no
`treatment during the second year. Patients who continued treatment in year 2 received a
`mean of 16 treatments out of a possible total 17 overall.
`The two trials enrolled patients with neovascular AMD characteristics including classic,
`occult, and mixed lesions of up to 12 disc areas and baseline visual acuity in the study eye
`between 20/40 and 20/320. The primary efficacy endpoint was the proportion of patients
`
`losing less than 15 letters of visual acuity, from baseline up to 54 week assessment.
`
`
`
`
`Reference ID: 3026883
`
`Regeneron Exhibit 1191.008
`Regeneron v. Novartis
`IPR2021-00816
`
`
`
`
`
` NDA 21-756/S-018
`Page 11
`
`
`
`
`
` Verteporfin PDT usage was permitted at the discretion of the investigators in patients with
`predominantly classic lesions.
`The groups treated with Macugen 0.3 mg exhibited a statistically significant result in both
`trials for the primary efficacy endpoint at 1 year: Study EOP1003, Macugen 73% vs. Sham
`
`60%; Study EOP1004, Macugen 67% vs. Sham 53%. Concomitant use of PDT overall was
`low. More sham treated patients (75/296) received PDT than Macugen 0.3 mg treated
`patients (58/294).
`On average, Macugen 0.3 mg treated patients and sham treated patients continued to
`
`experience vision loss. However, the rate of vision decline in the Macugen treated group was
`slower than the rate in the patients who received sham treatment. See Figure 1.
`Figure 1
`
`Mean Visual Acuity: Year 1
`
`
`
`
`
`At the end of the first year (week 54), approximately 1050 of the original 1200 patients were
`
`re-randomized to either continue the same treatment or to discontinue treatment through
`week 102. See Figure 2.
`Macugen was less effective during the second year than during the first year. The percentage
`of patients losing less than 15 letters from baseline to week 102 was: Study EOP1003,
`
`Macugen 38/67 (57%); Sham 30/54 (56%); Study EOP1004, Macugen 40/66 (61%); Sham
`18/53 (34%).
`
`
`
`
`
`Reference ID: 3026883
`
`Regeneron Exhibit 1191.009
`Regeneron v. Novartis
`IPR2021-00816
`
`
`
`
`
` NDA 21-756/S-018
`Page 12
`
`
`
`Figure 2
`
`Mean Visual Acuity: Year 2
`
`
`
`
`16
`
`17
`
`
`
`Dose levels above 0.3 mg did not demonstrate any additional benefit.
`
`The safety or efficacy of Macugen beyond 2 years has not been demonstrated.
`
`
`HOW SUPPLIED/STORAGE AND HANDLING
`Macugen (pegaptanib sodium injection) is supplied in a sterile foil pouch as a single-use
`glass syringe pre-filled with 0.3 mg of Macugen® in a nominal 90 µL deliverable volume
`
`pack. A sterile packaged BD® single use 30G x ½” Precision Glide® Luer Lok® needle is
`supplied in a separate pouch. The foil pouch and needle are packaged together in a carton
`(NDC 68782-001-02).
`Store in the refrigerator at 2° to 8°C (36° to 46°F). Do not freeze or shake vigorously.
`
`Rx only.
`
`
`
`
`
`
`PATIENT COUNSELING INFORMATION
`
`In the days following Macugen administration, patients are at risk for the development of
`
`endophthalmitis. If the eye becomes red, sensitive to light, painful or develops a change in
`
`vision, the patient should seek the immediate care with their ophthalmologist [see Warnings
`and Precautions (5.1)].
` MACUGEN®(pegaptanib sodium injection)
`
`Manufactured by:
`
`Gilead Sciences, Inc
`
`650 Cliffside Drive
`
`San Dimas, CA 91773
`
`
`For:
`
`Eyetech Inc.
`
`
`11360 Jog Road, Suite 200
`
`Palm Beach Gardens, Florida 33418
`
`
`BD and Precision Glide Luer Lok® are registered trademarks of Becton Dickinson & CO, Franklin
`Lakes, New Jersey 07417
`
`
`
`
`Reference ID: 3026883
`
`Regeneron Exhibit 1191.010
`Regeneron v. Novartis
`IPR2021-00816
`
`