Kala Pharmaceuticals, Inc. (NASDAQ:KALA), a biopharmaceutical company focused on the development and commercialization of therapeutics using its proprietary AMPPLIFY™ mucus-penetrating particle (MPP) Drug Delivery Technology, today announced that the New Drug Application (NDA) for KPI-121 0.25%, a product candidate for the temporary relief of signs and symptoms of dry eye disease utilizing a two-week course of therapy, has been accepted for review by the United States Food and Drug Administration (FDA). The FDA has set a target action date under the Prescription Drug User Fee Act (PDUFA) of August 15, 2019. If approved, KPI-121 0.25% is expected to be the first product indicated for the temporary relief of the signs and symptoms of dry eye disease, which would include treatment of dry eye flares.
“All currently marketed FDA-approved pharmaceutical treatments for dry eye disease are chronic therapies and are typically used in patients with chronic or persistent dry eye symptoms,” said Dr. Edward Holland, Director of Cornea Services, Cincinnati Eye Institute and Professor of Clinical Ophthalmology, University of Cincinnati. “The vast majority of patients experience episodic dry eye flares that are characterized by acute exacerbations of signs and/or symptoms. An FDA-approved, safe and effective short-term treatment for dry eye disease, including dry eye flares, will represent an important new treatment option for patients and prescribers.”
KPI-121 0.25% utilizes Kala’s proprietary AMPPLIFY Drug Delivery Technology to enhance penetration into target tissues of the eye. In preclinical studies, the AMPPLIFY technology increased delivery of loteprednol etabonate (LE) into ocular tissues more than three-fold compared to current LE products by facilitating penetration through the tear film mucins. The AMPPLIFY technology also underpins INVELTYS™ (loteprednol etabonate ophthalmic suspension) 1%, the first twice-a-day corticosteroid for the treatment of post-operative inflammation and pain following ocular surgery, which was approved by the FDA in August 2018.
The NDA submission for KPI-121 0.25% was supported by data from one Phase 2 and two Phase 3 efficacy and safety trials, STRIDE 1 and STRIDE 2 (STRIDE - Short Term Relief In Dry Eye), studying over 2,000 patients with dry eye disease. Based upon the FDA’s recommendation, Kala also initiated an additional Phase 3 clinical trial, STRIDE 3, in July 2018, evaluating KPI-121 0.25% for the temporary relief of the signs and symptoms of dry eye disease. The Company expects to report top-line results for STRIDE 3 in the fourth quarter of 2019.
Dry eye disease is a chronic, episodic, multifactorial disease affecting the tears and ocular surface that can result in tear film instability, inflammation, discomfort, visual disturbance and ocular surface damage. Dry eye disease is estimated to affect approximately 33 million people in the United States, based on an estimated prevalence of 14.5% as described in The Beaver Dam Offspring Study, a major epidemiological study published in 2014 in the American Journal of Ophthalmology. Dry eye disease can have a significant impact on quality of life and can potentially cause long-term damage to the ocular surface. In addition, the vast majority of dry eye patients experience acute exacerbations of their symptoms, which are commonly referred to as flares, at various times throughout the year. These flares can be triggered by numerous factors which cause ocular surface inflammation and impact tear production and/or tear film stability.
Kala is developing KPI-121 0.25% for the temporary relief of the signs and symptoms of dry eye disease utilizing a two-week course of therapy. Dry eye disease is a chronic, episodic, multifactorial disease affecting the tears and ocular surface and can involve tear film instability, inflammation, discomfort, visual disturbance and ocular surface damage. KPI-121 0.25% utilizes Kala's AMPPLIFY™ mucus-penetrating particle (MPP) Drug Delivery Technology to enhance penetration of loteprednol etabonate (LE) into target tissue of the eye. In preclinical studies, the AMPPLIFY Drug Delivery Technology increased delivery of LE into ocular tissues more than three-fold compared to current LE products by facilitating penetration through the tear film mucins. Kala has completed one Phase 2 and two Phase 3 clinical trials, STRIDE 1 and STRIDE 2 (STRIDE - Short Term Relief In Dry Eye), of KPI-121 0.25%. Kala believes that KPI-121 0.25%'s broad mechanism of action, rapid onset of relief of both signs and symptoms, favorable tolerability and safety profile and the potential to be complementary to existing therapies, could result in a favorable profile for the management of dry eye flares and other dry eye associated conditions. Kala has filed an NDA with the FDA and has been granted a PDUFA target action date of August 15, 2019. Based upon the FDA’s recommendation, Kala has also initiated an additional Phase 3 clinical trial in July 2018, STRIDE 3, evaluating KPI-121 0.25% for the temporary relief of the signs and symptoms of dry eye disease. Kala believes that it has identified key factors that contributed to the differences observed in the results from STRIDE 2 compared to those of STRIDE 1 and the Phase 2 study, and that changes made to the inclusion/exclusion criteria of STRIDE 3 based on these analyses will improve the probability of success. The Company expects to report top-line results for STRIDE 3 in the fourth quarter of 2019.
Kala is a biopharmaceutical company focused on the development and commercialization of therapeutics using its proprietary AMPPLIFY™ mucus-penetrating particle (MPP) Drug Delivery Technology, with an initial focus on the treatment of eye diseases. Kala has applied the AMPPLIFY Drug Delivery Technology to a corticosteroid, loteprednol etabonate (LE), designed for ocular applications, resulting in recently approved INVELTYS™ for the treatment of inflammation and pain following ocular surgery and its lead product candidate, KPI-121 0.25%, for the temporary relief of the signs and symptoms of dry eye disease.
Kala Pharmaceuticals , Inc .（ NASDAQ : KALA ），一家生物制药公司，专注于利用其专有的 AMPLIFY ™黏液穿透微粒（ MPP ）药物递送技术开发和商业化治疗药物，今天宣布 KPI-1210.25%的新药申请（ NDA ）。美国食品和药物管理局（ FDA ）已经接受了一种产品候选者，该产品可通过为期两周的治疗方案暂时缓解干眼病的症状和体征。FDA 已经根据2019年8月15日的处方药用户费用法案（ PDUFA ）设定了目标行动日期。如果获得批准，预计 KPI-1210.25%将是第一个用于暂时缓解干眼病症状和体征的产品，包括治疗干眼症。
辛辛那提大学辛辛那提眼科研究所 Corna Services 主任兼临床眼科教授 Edward Holland 博士说：“目前所有 FDA 批准的用于干眼病的药物治疗都是慢性疗法，通常用于慢性或持续性干眼症患者。”“绝大多数患者都经历过突发的干眼症，其特征是症状或体征的急性恶化。 FDA 批准的、安全有效的短期治疗干眼症，包括干眼症，将是患者和处方医生的一个重要的新治疗选择。”
KPI-1210.25%利用 Kala 的专有 AMPLIFY 药物递送技术，增强对眼睛目标组织的渗透。在临床前研究中， AMPLIFY 技术通过促进泪膜黏液的渗透，使荷花红醇非骨酸盐（ LE ）进入眼组织的时间比目前的 LE 产品增加了三倍以上。AMPLIFY 技术还支持 INVELLTYS ™（荷洛普列醇 etbonate 眼科悬液）1%，这是第一个每天两次用于治疗术后眼部手术后炎症和疼痛的皮质激素类药物，于2018年8月获得 FDA 批准。
KPI-1210.25%的 NDA 申请得到了来自一项2期和两项3期疗效和安全性试验 STRED 1和 STRED 2（ STRED-短时缓解干眼症）的数据支持，该试验研究了2000多名干眼病患者。根据 FDA 的建议， Kala 还于2018年7月启动了额外的3期临床试验 STRID 3，评估 KPI-1210.25%用于暂时缓解干眼病的症状和体征。公司预计将在2019年第四季度报告 STRID3的顶级业绩。
Kala 正在开发 KPI-1210.25%用于通过两周的治疗来暂时缓解干眼病的症状和体征。干眼病是一种影响泪水和眼表的慢性、偶发、多因素疾病，可涉及泪膜不稳定、炎症、不适、视力障碍和眼表损害。KPI-1210.25%利用 Kala 公司的 AMPLIFY ™黏液穿透微粒（ MPP ）药物传递技术，增强了荷花红醇骨酸盐（ LE ）对眼睛目标组织的渗透。在临床前研究中， AMPLIFY 药物传递技术通过促进泪膜黏液的渗透，使 LE 进入眼组织的量比目前的 LE 产品增加了三倍以上。Kala 已经完成了一项2期和两项3期临床试验，即 STRID1和 STRID2（ STRID-干眼短期缓解），分别为 KPI-1210.25%。Kala 认为 KPI-1210.25%的广泛性作用机制、快速缓解症状和体征、良好的耐受性和安全性以及对现有治疗方法的补充潜力，可能会对干眼片和其他干眼症的治疗产生有利的影响。Kala 已向 FDA 申报 NDA ，并已获得 PDUFA 目标诉讼日期为2019年8月15日。根据 FDA 的建议， Kala 还于2018年7月启动了额外的3期临床试验 STRID 3，评估 KPI-1210.25%用于暂时缓解干眼病的症状和体征。Kala 认为，它确定了造成 STREAD 2结果与 STRED 1和第2阶段研究结果之间差异的关键因素，并认为根据这些分析对 STRED 3的列入/排除标准所作的改变将提高成功的可能性。公司预计将在2019年第四季度报告 STRID3的顶级业绩。
Kala 是一家生物制药公司，专注于利用其专有的 AMPLIFY ™黏液穿透颗粒（ MPP ）药物递送技术开发和商业化治疗药物，最初专注于治疗眼病。Kala 公司已将 AMPLIFY 药物递送技术应用于一种皮质类固醇，为眼部应用而设计的 loteprednol etbonate ( LE )，导致最近批准的 INVELLTYS ™用于治疗眼部手术后的炎症和疼痛及其主要产品候选者 KPI-1210.25%。用于暂时缓解干眼病的症状和体征。