|Posted on March 17, 2021 at 7:15 PM|
The pipeline for dry eye disease drugs is beginning to heat up, with two biotechs announcing key developments, aiming to disrupt a market led by Allergan and Novartis.
Novartis paid Takeda $3.4 billion for its FDA-approved dry eye drug Xiidra during the Japanese pharma’s merger with Shire in 2019, outlining the sales potential in this market niche.
But with Novartis failing to convince European regulators about the merits of Xiidra last year, and Allergan’s ageing Restasis potentially facing generic competition, there’s a lot to play for and two biotechs are aiming to disrupt the market.
Sylentis, part of PharmaMar Group, has just announced FDA approval of a phase 3 trial for eye drops containing tivanisiran, in dry eye disease associated with Sjogren’s Syndrome.
The study design, involving more than 30 hospitals in the United States and 200 patients, has been approved by the FDA in 30 days and will be part of the marketing authorisation application, which will include another phase 3 trial.
Goals of the placebo-controlled study include efficacy (signs and symptoms) and safety of tivanisiran in patients with dry eye disease, associated with Sjögren’s Syndrome.
Tivanisiran is based on gene silencing technology using RNA interference (RNAi) and selectively inhibits production of the transient receptor potential cation channel (TRPV1).
The design of the protocol for the trial and its authorization are based on the scientific evidence of safety and efficacy obtained in the phase 3 HELIX trial.
This study showed a significant improvement in signs and symptoms in the subgroup of patients with Sjögren’s syndrome, which is a more severe form of dry eye disease.
Azura’s dry eye drug on target in phase 2
In a separate development, Israel-based Azura Ophthalmics said its potential dry eye drug AZR-MD-001 hit its target in a phase 2 trial, paving the way for further development.
AZR-MD-001, met its primary endpoints of showing improvements in both the signs and symptoms of dry eye disease caused by Meibomian gland dysfunction (MGD) reaching statistical significance compared to control in the two highest doses tested.
Around 86% of people with dry eye disease show symptoms of Meibomian gland dysfunction, where the glands that line the eyelids become blocked, preventing them from secreting enough oil into the tear film needed to properly lubricate the eye.
The company pointed out that current treatment options mainly focus on treating inflammation, which accounts for a “minority” of the dry eye disease population.
In an emailed interview, CEO Marc Gleeson, said results justify phase 3 development of AZR-MD-001.
He told pharmaphorum: “Given that there are 30 million patients in the US already diagnosed with dry eye disease – of which MGD is the root cause – with the majority not currently on a prescription treatment, this is a large market with high unmet need.
“Based on the topline results of our integrated analyses, AZR-MD-001 has the potential to be a first-in-class treatment option for patients with mild-to-moderate MGD. AZR-MD-001 is well-differentiated from other treatment options for MGD in a number of ways, including its formulation, mechanism of action and mode of delivery.”
Azura said it plans to announce results of its first registration study in the first half of 2022, with a $20 million funding round announced in October providing the financial backing.
Further fundraising will be needed to support a filing, Gleeson said and any additional funds will also be used to advance the company’s pipeline of novel ophthalmic drugs.
Gleeson added: “With that said, we are open to all options, including evaluating partnerships that will help bring this medicine to those suffering from the debilitating symptoms of MGD.”
Aldeyra Therapeutics Announces Positive Top-Line Symptom and Sign Results from Run-In Cohort of Phase 3 TRANQUILITY Trial in Dry Eye Disease
|Posted on January 24, 2021 at 6:55 AM|
LEXINGTON, Mass.--(BUSINESS WIRE)--Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra) today announced positive top-line symptom, redness, and Schirmer’s test results from the run-in cohort of the Phase 3 TRANQUILITY clinical trial in patients with dry eye disease.
The double-masked, single-center, parallel-group run-in cohort enrolled 23 patients: 12 patients were randomized to receive 0.25% reproxalap ophthalmic solution and 11 patients were randomized to receive vehicle ophthalmic solution. Patients received four doses one day prior to and two doses on the day of exposure to a 90-minute dry eye chamber with minimal humidity, high airflow, and forced visual tasking.
Over all time points in aggregate in the dry eye chamber, reproxalap was observed to be statistically superior to vehicle for the two assessed symptoms, visual analog scale (VAS) ocular dryness score (p = 0.001) and ocular discomfort score (p < 0.0001) in the run-in cohort of TRANQUILITY. Consistent with previously announced allergen chamber Phase 2 clinical trial results, reproxalap demonstrated statistically significant improvement over vehicle (p = 0.03) in ocular redness, an objective sign of dry eye disease. Improvement in ocular symptoms and redness occurred within minutes after reproxalap dosing. Following acute dosing on the day prior to the dry eye chamber, Schirmer test scores were directionally in favor of reproxalap over vehicle, and reproxalap was statistically superior to vehicle in improvement in VAS dryness score (p = 0.003), ocular discomfort 4-symptom questionnaire (OD4SQ) dryness score (p = 0.006), OD4SQ grittiness score (p = 0.006), and OD4SQ discomfort score (p = 0.003). Consistent with clinical experience in over 1,100 patients, no adverse findings on safety assessments were observed, and reproxalap was well-tolerated.
“The symptom improvement observed in the run-in cohort of TRANQUILITY announced today support the first-line potential use of reproxalap in dry eye disease, and represent the first results from an ophthalmic solution for chronic use that demonstrate activity acutely following drug administration,” stated Todd C. Brady, M.D., Ph.D., President and Chief Executive Officer of Aldeyra. “The activity of reproxalap in reducing ocular redness, initially demonstrated in the allergen chamber Phase 2 clinical trial, was also observed in the dry eye chamber run-in results of TRANQUILITY, and we look forward to initiating enrollment of the main cohort.”
Among many patients and physicians, current dry eye disease therapies are considered inadequate. Discontinuation rates for lifitegrast and cyclosporine, which currently comprise standard of care, exceed 60% within 12 months of initiation of therapy, in part due to delayed onset of effect.
“The potential for patients to experience acute symptomatic relief and observe rapid improvement in ocular redness after the initiation of therapy represents a new possible paradigm in dry eye disease treatment and could offer significant clinical advantage over existing therapies, which often require weeks of drug administration before patients experience even moderate improvement,” stated Victor Perez, M.D., Professor of Ophthalmology at Duke University School of Medicine and a member of Aldeyra’s Anterior Segment Scientific Advisory Board.
The main cohort of TRANQUILITY is expected to begin enrollment in February 2021, following completion of tear RASP analysis from the run-in cohort and confirmation of endpoints and number of subjects. Results from TRANQUILITY are expected in the second half of 2021. A second Phase 3 clinical trial, TRANQUILITY-2, is expected to initiate in the first quarter of 2021.
IACTA Pharmaceuticals and Pharmaleads to Develop the World's First Epithelial Protective Drug Harnessing Endogenous Analgesia for the Topical Treatment of Acute and Chronic Ocular Pain
|Posted on January 10, 2021 at 7:55 AM|
- Ocular Pain, a $10+ billion global market, with significant unmet medical need
- License agreement aims to accelerate global development of DENKIs, leveraging expertise and resources of both companies
Irvine, Calif., Paris, Hong Kong, Jan. 7, 2021 /PRNewswire/ — IACTA Pharmaceuticals, Inc. (“IACTA" and Pharmaleads, with Pharmaleads Greater China, today announced they have entered into licensing agreements, with IACTA acquiring global rights to Pharmaleads’ Dual Enkephalinase Inhibitors (DENKI®, a novel class of non-opioid compounds for the treatment of acute and chronic ocular pain.
“With this agreement, IACTA and Pharmaleads will collaborate to develop next-generation pain treatments to help the millions of people across the globe living with the debilitating effects of ocular pain,” said Damon Burrows, CEO of IACTA. “We believe that the epithelial protective properties of DENKI observed in preclinical studies, combined with its pain-relieving properties will revolutionize eye care.”
The epithelial protective promise of DENKI, combined with its pain-relieving properties will revolutionize eye care.
“Today’s announcement further exemplifies IACTA’s business momentum, as we continue to foster research and development initiatives to address unmet medical needs in the global eye care market,” continued Damon Burrows.
Under the terms of these agreements, Pharmaleads and Pharmaleads Greater China have granted IACTA an exclusive, worldwide, royalty-bearing license to lead the clinical and commercial development of IC800 (acute) and IC805 (chronic) and other DENKI drugs from Pharmaleads’ portfolio. Pharmaleads and Pharmaleads Greater China will together be eligible to receive up to $100M in total deal value including upfront, development, regulatory, and commercial milestone payments. Based on the ocular preclinical package already available and human systemic safety data, IACTA expects to start human proof of concept trials in ocular pain in 2021. IACTA’s ophthalmic drug development expertise combined with Pharmaleads breakthrough discoveries will work to bring to market the world’s first non-opioid, epithelial protective drug harnessing endogenous analgesia for the treatment of chronic (i.e., neuropathic pain and dry eye) and acute (e.g., post-surgical) ocular pain, which is estimated to affect more than 175 million people globally.
“We are thrilled to be partnering with IACTA, as we remain focused on advancing our pipeline of candidates targeting pain management, including a program for acute migraine headache. This partnership will give us the opportunity to accelerate the development of our drugs and to bring alternative non-addictive pain treatments to address the opiate crisis,” said Tanja Ouimet, PhD, COO of Pharmaleads. “IACTA’s expertise in the development of ocular drugs will reveal the full potential of DENKI-based treatments to protect and extend the life of enkephalins expressed locally on the eye surface and work to bring the first dedicated ocular pain treatments to the market and to many suffering patients who currently have no treatment for their pain besides NSAIDs or opiates.”
“This partnership stands for a pivotal move towards our organization’s overall strategic direction to foster opportunities for delivering transformative treatments which at the same time puts the human aspect of medicine in focus,” said Tian Ye, CEO of Pharmaleads Greater China. “We believe that as a first-of-its-kind treatment in non-addictive pain management, this breakthrough alternative has unprecedented potential in addressing unmet medical needs in eye care.”
“DENKI has the potential to transform the treatment of ocular pain, advance patient care, and become one of the most significant scientific innovations for the eye care industry.” said Taryn Conway, former Associate Vice President of Marketing, for Allergan, Inc., and Strategic Advisor to IACTA Pharmaceuticals.
“Ocular pain management, whether as a disease or a symptom, has been hampered by the lack of local, non-epithelial-toxic analgesics,” said Dr. Marjan Farid Director of the Cornea, Cataract, and Refractive Surgery and Vice Chair of Ophthalmic Faculty at the Gavin Herbert Eye Institute. “DENKIs could provide the first chronic pain management option for the millions of patients suffering from ocular pain and be a true game-changer in the field of ophthalmic therapeutics.”
DENKIs (Dual ENKephalinase inhibitors) aim to protect enkephalins from degradation, hence increasing their local concentrations and thereby inducing a physiological analgesia, which improves pain management.
About IACTA Pharmaceuticals, Inc.
IACTA is an ophthalmic focused pharmaceutical company led by former top executives from one of the leading eye care companies in the world, Allergan. The company currently has six products in development for major market opportunities. The Company’s lead product, IC 265, is ready to enter a Phase 2 clinical study with data outcomes expected in 2022. For more information on IACTA Pharmaceuticals, Inc., visit www.iactapharma.com
In addition, this announcement comes on the heels of the recent agreement between IACTA Pharmaceuticals, Inc. and Zhaoke (Hong Kong) Ophthalmology Pharmaceutical Limited (“ZKO”;), on the licensing of two of the Company’s products, IC 265 for dry eye and IC 270 for allergic conjunctivitis.
Headquartered in Paris, Pharmaleads, with its sister company Pharmaleads Greater China, is a clinical stage private biotech company creating and developing innovative non-opiate, non-addictive products for the management of acute and chronic moderate to severe pain, a growing market with significant unmet medical need. Pharmaleads’ drugs are based on its deep knowledge and understanding of the metabolism of enkephalins, a key element of the body’s natural pain management system.
Pharmaleads has two products in clinical development, targeting multi-billion-dollar markets: chronic neuropathic pain (oral), post-surgical/breakthrough cancer pain as a substitute for injectable opiates (intravenous.), and acute migraine headache (oral). Pharmaleads is also collaborating with academic partners to explore the potential therapeutic actions of IC800 in opiate use and withdrawal disorders.
For more information about Pharmaleads please visit www.Pharmaleads.com
Any statements in this press release that are not historical facts are forward-looking statements made under the provisions of the Private Securities Litigation Reform Act of 1995. Any forward-looking statements involve risks and uncertainties that could cause actual results to be materially different from historical results or any future results expressed or implied by such forward-looking statements. Such statements include the potential for IC800 and IC805 and the development of IC 265 and IC 270. Any forward-looking statements in this press release represent the Company’s views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. The Company specifically disclaims any obligation to update this information as a result of future events or otherwise, except as required by applicable law.
|Posted on November 28, 2020 at 7:00 AM|
SilkTech Biopharmaceuticals has completed enrollment in a phase 2b clinical trial of SDP-4, its eye drop formulation for the treatment of the signs and symptoms of dry eye disease, according to a press release.
The randomized, double-masked, vehicle-controlled, multicenter trial is evaluating the safety and efficacy of SDP-4 at 0.1%, 1% and 3% concentrations in 305 patients at 25 U.S. sites.
SDP-4, a biotherapeutic naturally derived from silk protein, is designed to utilize a dual mechanism of action to physically improve tear film stability and reduce inflammation to treat dry eye. It also inhibits kinase activation of the NF-kB gene transcription pathway.
“Our team has accomplished a significant milestone in reaching full enrollment of our first-in-human ophthalmic study for a silk protein-derived biotherapeutic,” Brian Lawrence, PhD, SilkTech CEO, said in the release. “The trial enrolled 6 weeks ahead of projected schedule indicating the significant and growing need for new therapeutic approaches to this debilitating disease.”
Topline data are expected to be reported by the end of this year’s fourth quarter.
|Posted on November 16, 2020 at 8:20 AM|
A phase 2b clinical trial of AR-15512 ophthalmic solution for the treatment of dry eye disease has been initiated, according to a press release from Aerie Pharmaceuticals.
COMET-1 is a randomized, double-masked, vehicle-controlled trial investigating the safety and efficacy of AR-15512, a TRPM8 agonist. The trial aims to enroll about 360 patients who will receive AR-15512 0.0014%, AR-15512 0.003% or AR-15512 vehicle, one drop twice daily in each eye for 3 months. Primary endpoints include ocular discomfort and tear production, and patients will be evaluated at days 14, 28 and 84, the release said.
“By activating the TRPM8 receptor, AR-15512 may stimulate tear production as well as reduce ocular discomfort through a mild cooling sensation. We anticipate topline results of COMET-1, which is powered as a phase 3, in the third quarter of 2021,” Vicente Anido Jr., PhD, Aerie chairman and CEO, said in the release.