2018年12月3日，眼科治疗公司，一家专注于眼部疾病和眼病创新疗法的制定、开发和商业化的生物制药公司，今天宣布美国食品和药物管理局（FDA）已批准DEXTENZA（地塞米松眼用插入物）0.4mg用于眼科手术后眼痛的小管内治疗。

公司总裁兼首席执行长安东尼·马特西奇（Antony Mattessich）说：“我们非常高兴地宣布，德克森美孚获得批准，是在我们进行审批前不久，比PDUFA日期提前了大约一个月。”“就在一年多前，我们开始加强我们的科学和配方的专业知识，与个人谁有技能和经验，以创建一流的团队，以获得德士坦ZA批准，并成为商业阶段的生物制药公司。

我们认为，这一批准是对药物输送技术平台的主要外部验证，也是对在Ocular公司发生的转变的一种重要外部验证。虽然我们对我们的第一种药物产品的批准感到兴奋，但我们的目标一直是在短期内将DEXTENZA带给尽可能多的患者，并通过使滴剂过时来革新眼科药物输送。

  DEXTENZA是FDA批准的第一个单次应用地塞米松治疗术后30天眼痛的小管内植入物。DEXTENZA的批准是基于(i)在两项随机的、车辆控制的3期研究中证明的有效性，其中白内障术后第8天受试者无痛的发生率显著高于车辆对照组，以及(i i)在两项Ph中的安全性。ASE 3研究以及第三个随机、车辆控制的阶段2研究。

该公司认为，交付概况代表了有区别的和潜在的转变为病人和医生的新产品。对于病人，DEXTENZA提供方便的全程手术后类固醇治疗与医生的一次性放置一个单一的插管。DEXTENZA有潜力取代在当前护理标准下需要最多70滴局部类固醇滴眼液的复杂滴眼方案。

  首席医师迈克尔·戈德斯坦（Michael Goldstein）医学博士说：“眼科手术后服用眼药水的依从性对患者来说非常具有挑战性，也是外科医生关心的问题。”“DEXTENZA的批准为外科医生提供了在手术后放置单一药物插入物使用无防腐剂的类固醇治疗患者的机会。有了这个产品，患者就可以从眼科手术后使用类固醇滴眼液的繁重方案中解放出来。”

  dextenza®标签
  dextenza®（地塞米松ophthalmic插入）是一corticosteroid表明治疗后的疼痛ophthalmic眼部手术。

dextenza是免费的防腐剂ophthalmic插入是插入在较低的canaliculus和泪小点。dextenza 0.4毫克单剂量地塞米松的释放（在30天内到插入。

dextenza是resorbable和不需要去除。盐水灌溉或表达可以手动执行的插入到删除如有必要。dextenza是仅用于单次使用。

在两个研究dextenza随机，多中心，双盲，平行组，车辆控制的临床试验患者的第三期，与接收dextenza或其车辆立即在完成白内障手术。在研究1，80%的患者组（n=dextenza（164）在8天的疼痛无相比车辆处理的43 %的患者（n=83）（P＜0.0001）。在研究277%的患者dextenza组（N = 161）（8）疼痛无天相比车辆处理59%的患者（n=80）（P=0.025）。
安全评估是从双相3相2的临床试验和临床试验。总的来说，接触到dextenza为351人。不良反应最常见的受试者中治疗眼与dextenza）：包括iritis inflammation前房和iridocyclitis（9%），增加眼内压力（5%），视力下降，眼痛（2分）（1%），黄斑水肿cystoid（1%），角膜水肿（1%），和conjunctival HY充血（1%）。最常见的不良事件是非眼性头痛（1%）。
  dextenza®重要安全信息
  在判断一contraindicated dextenza活性角膜上皮小管conjunctival或感染，包括单纯疱疹病毒，牛痘病毒（keratitis树突状keratitis），和mycobacterial水痘感染；真菌；眼睛疾病；和泪囊炎的疗效。
  长时间使用激素可导致青光眼视神经损害的缺陷，视力和视觉领域。类固醇激素与应用》中存在的眼内压和青光眼的治疗过程中应监测。
激素可以抑制宿主反应，从而增加眼部感染的危险性是次要的。在急性感染purulent条件下，类固醇激素可以增强现有的掩模和感染。
使用类固醇激素可以在球场prolong眼和可能的许多病毒感染的严重程度exacerbate之眼（包括单纯疱疹）。
侵袭性真菌性角膜必须被视为在任何ulceration类固醇已被使用，或是在使用。应该采取适当的真菌培养时。
使用类固醇激素治疗白内障手术后的发病率和可能增加的延迟bleb）的形成。
  请参见重要的安全信息和完整的信息在www.dextenza.com prescribing/http://www.dextenza.com/wp-content/uploads/2018/12/DEXTENZA-Final-Label-12.1.18.pdf
  关于dextenza®
  dextenza®（地塞米松0.4 FDA批准的ophthalmic插入）是在手术后疼痛的治疗ophthalmic眼。dextenza是放置在孔内插入corticosteroid自然张开，在内部部分和较低的eyelid入，设计了一种canaliculus和地塞米松眼交付从表面到30天没有防腐剂。dextenza吸收和退出的鼻泪管系统不需要被清除。
  关于眼therapeutix股份有限公司
  眼部给药是一therapeutix股份有限公司，公司专注于开发和商业化的公式，研究创新的方法，疾病和条件，利用其专有的眼睛bioresorbable基于水凝胶配方技术。商业therapeutix第一眼的药物制品，是FDA批准的dextenza®，眼痛ophthalmic治疗后手术。OTX（内插），曲伏前列素）是一种在临床开发的相位内插（3）在眼内压力减少患者与原发性高血压患者的眼和开角型青光眼。在早期阶段的公司和资产，包括扩展的OTX，前房内植入给药的曲伏前列素减少眼内压力的眼高血压和青光眼患者和持续的释放，以及intravitreal视网膜疾病的治疗应用。这些应用包括intravitreal OTX -酪氨酸激酶抑制剂，含有抑制剂（TKI），和，在协作与regeneron IVT，OTX，扩展到基于蛋白-抗血管内皮生长因子（VEGF）的陷阱。第一眼therapeutix’s的产品，是美国FDA批准的resure®密封胶，密封incisions白内障手术对角膜后。

DEXTENZA®
(dexamethasone) Ophthalmic Insert 0.4 mg, for Intracanalicular Use

DEXTENZA (dexamethasone ophthalmic insert) is a fluorescent yellow, 3 mm cylindrical-shaped, resorbable, sterile insert for intracanalicular use. DEXTENZA contains 0.4 mg dexamethasone in a polyethylene glycol (PEG) based hydrogel conjugated with fluorescein. DEXTENZA does not contain an antimicrobial preservative. The active ingredient is represented by the chemical structure:

The chemical name for dexamethasone is 9-Fluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione. It has a molecular formula of C22H29FO5 and a molecular weight of 392.47 g/mol. Dexamethasone is a crystalline powder.

0.4 mg dexamethasone.

4-arm polyethylene glycol (PEG) N-hydroxysuccinimidyl glutarate (20K), trilysine acetate, N-hydroxysuccinimide-fluorescein, sodium phosphate dibasic, sodium phosphate monobasic, water for injection.

Indications & Dosage

DEXTENZA® (dexamethasone ophthalmic insert) is a corticosteroid indicated for the treatment of ocular pain following ophthalmic surgery.

DEXTENZA is an ophthalmic insert that is inserted in the lower lacrimal punctum into the canaliculus. A single DEXTENZA releases a 0.4 mg dose of dexamethasone for up to 30 days following insertion.

DEXTENZA is resorbable and does not require removal. Saline irrigation or manual expression can be performed to remove the insert if necessary. DEXTENZA is intended for single-use only.

Do not use if pouch has been damaged or opened. Do not re-sterilize.

1. Carefully remove foam carrier and transfer to a clean and dry area.

2. If necessary, dilate the punctum with an ophthalmic dilator. Care should be taken not to perforate the canaliculus during dilation or insertion of DEXTENZA. If perforation occurs, do not insert DEXTENZA.

3. After drying the punctal area, using blunt (non-toothed) forceps, grasp DEXTENZA and insert into the lower lacrimal canaliculus. DEXTENZA should be placed just below the punctal opening. Excessive squeezing of DEXTENZA may cause deformation.

4. To aid in the hydration of DEXTENZA, 1 to 2 drops of balanced salt solution can be instilled into the punctum. DEXTENZA hydrates quickly upon contact with moisture. If DEXTENZA begins to hydrate before fully inserted, discard the product and use a new DEXTENZA.

5. DEXTENZA can be visualized when illuminated by a blue light source (e.g., slit lamp or hand held blue light) with yellow filter.

Ophthalmic insert: fluorescent yellow, 3 mm cylindrical-shaped insert containing dexamethasone, 0.4 mg.

DEXTENZA is supplied sterile in a foam carrier within a foil laminate pouch containing:

NDC 70382-204-10     Carton containing 10 pouches (10 inserts)
NDC 70382-204-01     Carton containing 1 pouch (1 insert)

Do not use if pouch has been damaged or broken.

DEXTENZA is intended for single dose only.

Store refrigerated, between 2°C and 8°C (36°F and 46°F). Do not freeze. Protect from light, keep in package until use.

Manufactured by: Ocular Therapeutix™ Ocular Therapeutix, Inc. Bedford, MA 01730 USA. Revised: Nov 2018

Side Effects & Drug Interactions

The following serious adverse reactions are described elsewhere in the labeling:

· Intraocular Pressure Increase [see WARNINGS AND PRECAUTIONS]

· Bacterial Infection [see WARNINGS AND PRECAUTIONS]

· Viral Infection [see WARNINGS AND PRECAUTIONS]

· Fungal Infection [see WARNINGS AND PRECAUTIONS]

· Delayed Healing [see WARNINGS AND PRECAUTIONS]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation; delayed wound healing; secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera [see WARNINGS AND PRECAUTIONS].

DEXTENZA was studied in three randomized, vehicle-controlled studies (n = 351) The mean age of the population was 68 years (range 43 to 87 years), 62% were female, and 85% were white. Forty-six percent had brown iris color and 31% had blue iris color. The most common ocular adverse reactions that occurred in patients treated with DEXTENZA were: anterior chamber inflammation including iritis and iridocyclitis (9%); intraocular pressure increased (5%); visual acuity reduced (2%); eye pain (1%); cystoid macular edema (1%); corneal edema (1%); and conjunctival hyperemia (1%). The most commonly reported adverse reactions that occurred in 1-6% of patients treated with DEXTENZA were increases in intraocular pressure, anterior chamber inflammation, iritis, visual acuity reduced, corneal edema, cystoid macular edema, eye pain, and conjunctival hyperemia.

The most common non-ocular adverse reaction that occurred in patients treated with DEXTENZA was headache (1%).

No Information Provided

Warnings & Precautions

Included as part of the "PRECAUTIONS" Section

Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. Steroids should be used with caution in the presence of glaucoma. Intraocular pressure should be monitored during the course of the treatment.

Corticosteroids may suppress the host response and thus increase the hazard for secondary ocular infections. In acute purulent conditions, steroids may mask infection and enhance existing infection [see CONTRAINDICATIONS].

Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex) [see CONTRAINDICATIONS].

Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. Fungal culture should be taken when appropriate [see CONTRAINDICATIONS].

The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation.

No adequate studies in animals have been conducted to determine whether DEXTENZA has the potential for carcinogenesis.

Dexamethasone was not mutagenic in the Ames/Salmonella assay, both with and without metabolic activation. Dexamethasone was genotoxic in twoin vitro assays using human lymphocytes (chromosomal aberration assay and sister chromatid exchange assay) and was genotoxic in two mousein vivo assays (micronucleus assay and sister chromatid exchange assay).

Fertility studies have not been conducted in animals using DEXTENZA.

There are no adequate or well-controlled studies with DEXTENZA in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, administration of topical ocular dexamethasone to pregnant mice and rabbits during organogenesis produced embryofetal lethality, cleft palate and multiple visceral malformations [see Animal Data].

Animal Data

Topical ocular administration of 0.15% dexamethasone (0.75 mg/kg/day) on gestational days 10 to 13 produced embryofetal lethality and a high incidence of cleft palate in a mouse study. A daily dose of 0.75 mg/kg/day in the mouse is approximately 5 times the entire dose of dexamethasone in the DEXTENZA product, on a mg/m2 basis. In a rabbit study, topical ocular administration of 0.1% dexamethasone throughout organogenesis (0.36 mg /day, on gestational day 6 followed by 0.24 mg/day on gestational days 7-18) produced intestinal anomalies, intestinal aplasia, gastroschisis and hypoplastic kidneys. A daily dose of 0.24 mg/day is approximately 6 times the entire dose of dexamethasone in the DEXTENZA product, on a mg/m2 basis.

Systemically administered corticosteroids appear in human milk and could suppress growth and interfere with endogenous corticosteroid production; however the systemic concentration of dexamethasone following administration of DEXTENZA is low [see CLINICAL PHARMACOLOGY]. There is no information regarding the presence of DEXTENZA in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production to inform risk of DEXTENZA to an infant during lactation. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for DEXTENZA and any potential adverse effects on the breastfed child from DEXTENZA.

Safety and effectiveness in pediatric patients have not been established.

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Overdosage & Contraindications

No Information Provided

DEXTENZA is contraindicated in patients with active corneal, conjunctival or canalicular infections, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella; mycobacterial infections; fungal diseases of the eye, and dacryocystitis.

Clinical Pharmacology

Dexamethasone, a corticosteroid, has been shown to suppress inflammation by inhibiting multiple inflammatory cytokines resulting in decreased edema, fibrin deposition, capillary leakage and migration of inflammatory cells.

Plasma samples were obtained from 16 healthy volunteers prior to insertion of DEXTENZA and on Day 1 (at 1, 2, 4, 8, 16 hours), 2 (24 hours), 4, 8, 15, 22 and 29 following the insertion of DEXTENZA.

Plasma concentrations of dexamethasone were detectable (above 50 pg/mL, the lower limit of quantification of the assay) in 11% of samples (21 of 189), and ranged from 0.05 ng/mL to 0.81 ng/mL.

In two randomized, multicenter, double-masked, parallel group, vehicle-controlled trials, patients received DEXTENZA or its vehicle immediately upon completion of cataract surgery. In both trials, DEXTENZA had a higher incidence of subjects who were pain free at all post-operative days. Results are shown in Table 1.

Table 1: Percentage of Pain-Free Patients

Medication Guide

Advise patients to consult their surgeon if pain, redness, or itching develops.