The purpose of this study is to evaluate the proportion of ocular adverse events reported in subjects with dry eye disease (DED) between the intervention arm (0.003% AR-15512) and Refresh® Classic.

Start Date01 Jan 2025

Sponsor / Collaborator

Alcon Research Ltd.

NCT06544707 / RecruitingPhase 3

A Phase 3b Open-Label Study Designed to Evaluate Tear Production Stimulated by 0.003% AR-15512

The purpose of this study is to evaluate tear production following acute administration of AR-15512 ophthalmic solution 0.003% (0.003% AR-15512) in subjects with dry eye disease (DED).

Start Date15 Oct 2024

Sponsor / Collaborator

Alcon Research Ltd.

NCT06544694 / RecruitingPhase 3

A Phase 3b Study to Investigate the Effect of 0.003% AR-15512 on the Ocular Surface Characteristics of Subjects With Dry Eye Disease

The purpose of this study is to evaluate the effect of AR-15512 ophthalmic solution 0.003% (0.003% AR-15512) on ocular surface characteristics of subjects with dry eye disease (DED).

Start Date08 Oct 2024

Sponsor / Collaborator

Alcon Research Ltd.

100 Clinical Results associated with Acoltremon

100 Translational Medicine associated with Acoltremon

100 Patents (Medical) associated with Acoltremon

Literatures (Medical) associated with Acoltremon

01 Oct 2022·The Ocular Surface

A randomized, vehicle-controlled, Phase 2b study of two concentrations of the TRPM8 receptor agonist AR-15512 in the treatment of dry eye disease (COMET-1)

Article

Author: Wirta, David L ; Lewis, Amber E ; Ousler, George W ; Senchyna, Michelle ; Evans, David G ; McLaurin, Eugene B ; Hollander, David A

PURPOSEDry eye disease (DED) symptoms can negatively impact quality of life (QoL). AR-15512, a transient receptor potential melastatin 8 (TRPM8) agonist, was evaluated as a potential therapy for DED.METHODSIn a Phase 2b study, patients with DED were randomized 1:1:1 to 0.0014% AR-15512, 0.003% AR-15512, or vehicle twice daily for 12 weeks. Eligibility criteria included DED signs and symptoms of prespecified severity levels. Outcomes assessed were DED signs (Schirmer score ± anesthetic, ocular surface staining, hyperemia), symptoms (Ocular Discomfort [ODS-VAS], Symptoms Assessment iN Dry Eye [SANDE], Eye Dryness-VAS, Ocular Pain-VAS), QoL-VAS, and adverse events. Co-primary endpoints were changes from baseline in ODS-VAS and anesthetized Schirmer score at Day 28.RESULTS0.003% AR-15512 (n = 122) was associated with early and sustained improvements in unanesthetized Schirmer score (Days 1 and 14, p < 0.0001), as well as improvements in ocular surface staining (Days 14 and 84, p ≤ 0.0365) and hyperemia (Day 84, p < 0.0215). Statistically significant improvements in symptoms were observed for the 0.003% concentration on SANDE (Days 14, 28, and 84, p ≤ 0.0254), ODS-VAS (Day 84, p = 0.0281), Eye Dryness-VAS (Day 84, p = 0.0302), and multiple QoL measures (Days 14, 28, and 84, p < 0.05). There were no significant differences between active and vehicle groups for the co-primary endpoints. The most common adverse events were burning and stinging upon instillation.CONCLUSIONSAlthough predefined co-primary study endpoints were not met, AR-15512 demonstrated statistically significant improvements in DED signs, symptoms, and disease-related QoL.

01 Sep 2010·Experimental DermatologyQ3 · MEDICINE

Topical application of TRPM8 agonists accelerates skin permeability barrier recovery and reduces epidermal proliferation induced by barrier insult: role of cold‐sensitive TRP receptors in epidermal permeability barrier homoeostasis

Q3 · MEDICINE

Article

Author: Sumiko Denda ; Moe Tsutsumi ; Mitsuhiro Denda

Please cite this paper as: Topical application of TRPM8 agonists accelerates skin permeability barrier recovery and reduces epidermal proliferation induced by barrier insult: role of cold‐sensitive TRP receptors in epidermal permeability barrier homoeostasis. Experimental Dermatology 2010; 19: 791–795.Abstract: TRPA1 and TRPM8 receptors are activated at low temperature (A1: below 17°C and M8: below 22°C). Recently, we observed that low temperature (below 22°C) induced elevation of intracellular calcium in keratinocytes. Moreover, we demonstrated that topical application of TRPA1 agonists accelerated the recovery of epidermal permeability barrier function after disruption. In this study, we examined the effect of topical application of TRPM8 modulators on epidermal permeability barrier homoeostasis. Immunohistochemical study and RT‐PCR confirmed the expression of TRPM8 or TRPM8‐like protein in epidermal keratinocytes. Topical application of TRPM8 agonists, menthol and WS 12 accelerated barrier recovery after tape stripping. The effect of WS12 was blocked by a non‐selective TRP antagonist, Ruthenium Red, and a TRPM8‐specific antagonist, BTCT. Topical application of WS12 also reduced epidermal proliferation associated with barrier disruption under low humidity, and this effect was blocked by BTCT. Our results indicate that TRPM8 or a closely related protein in epidermal keratinocytes plays a role in epidermal permeability barrier homoeostasis and epidermal proliferation after barrier insult.

01 Jan 2010·Molecular PainQ3 · MEDICINE

Sensitization of Capsaicin and Icilin Responses in Oxaliplatin Treated Adult Rat DRG Neurons

Q3 · MEDICINE

ArticleOA

Author: Anand, Praveen ; Anand, Uma ; Otto, William R

Background: Oxaliplatin chemotherapy induced neuropathy is a dose related cumulative toxicity that manifests as tingling, numbness, and chronic pain, compromising the quality of life and leading to discontinued chemotherapy. Patients report marked hypersensitivity to cold stimuli at early stages of treatment, when sensory testing reveals cold and heat hyperalgesia. This study examined the morphological and functional effects of oxaliplatin treatment in cultured adult rat DRG neurons. Results: 48 hour exposure to oxaliplatin resulted in dose related reduction in neurite length, density, and number of neurons compared to vehicle treated controls, using Gap43 immunostaining. Neurons treated acutely with 20 μg/ml oxaliplatin showed significantly higher signal intensity for cyclic AMP immunofluorescence (160.5 ± 13 a.u., n = 3, P < 0.05), compared to controls (120.3 ± 4 a.u.). Calcium imaging showed significantly enhanced capsaicin (TRPV1 agonist), responses after acute 20 μg/ml oxaliplatin treatment where the second of paired capsaicin responses increased from 80.7 ± 0.6% without oxaliplatin, to 171.26 ± 29% with oxaliplatin, (n = 6 paired t test, P < 0.05); this was reduced to 81.42 ± 8.1% (P < 0.05), by pretretreatment with the cannabinoid CB2 receptor agonist GW 833972. Chronic oxaliplatin treatment also resulted in dose related increases in capsaicin responses. Similarly, second responses to icilin (TRPA1/TRPM8 agonist), were enhanced after acute (143.85 ± 7%, P = 0.004, unpaired t test, n = 3), and chronic (119.7 ± 11.8%, P < 0.05, n = 3) oxaliplatin treatment, compared to control (85.3 ± 1.7%). Responses to the selective TRPM8 agonist WS-12 were not affected. Conclusions: Oxaliplatin treatment induces TRP sensitization mediated by increased intracellular cAMP, which may cause neuronal damage. These effects may be mitigated by co-treatment with adenylyl cyclase inhibitors, like CB2 agonists, to alleviate the neurotoxic effects of oxaliplatin.

News (Medical) associated with Acoltremon

12 Aug 2024

·www.prnewswire.com

OcuMension acquires rights to Alcon eye drops in exchange for a 16.7% equity stake, signaling the commencement of comprehensive strategic relationship

SHANGHAI, Aug. 12, 2024 /PRNewswire/ -- On August 13th 2024, Ocumension Therapeutics (" OcuMension") announced an agreement with Alcon Inc. (" Alcon", and collectively with OcuMension, the " Parties") where OcuMension will acquire or secure commercialization rights in China to a portfolio of Alcon dry eye treatments and procedural drops, including several commercially available products and one development-stage product. The scope of the agreement will also cover areas of R&D, manufacturing and commercialization in China. In connection with the transfer of these rights, OcuMension will issue 139,161,120 shares to Alcon, accounting for 16.71% of the total share capital (post-issuance). Consequently, Alcon becomes one of the largest shareholders of OcuMension. Under the terms of the arrangement, each company has granted the other company a right of first negotiation over future products. OcuMension, as a leading Chinese ophthalmic pharmaceutical platform company, focuses on integrating comprehensive capabilities across the entire lifecycle of ophthalmic drug development—from research and development to commercialization. OcuMension possesses a portfolio of 25 pharmaceutical assets. Alcon, the global leader in eye care, offers a broad portfolio of products to enhance sight and improve lives for patients in more than 140 countries. Under this arrangement, OcuMension will acquire outright, Tears Natural® Forte, Bion Tears, Alcaine®, Fluorescite, and Cyclogyl, in the Chinese market and the commercialization rights in China to Systane® Ultra and AR-15512, a novel topical drug candidate for dry eye. Under the terms of this agreement, OcuMension will manufacture those products acquired outright for China after a transition period. OcuMension will also develop, manufacture and commercialize AR-15512 in China. The addition of these seven mature products and AR-15512 to OcuMension's portfolio is expected to further enhance OcuMension's leadership in the ophthalmology field in the China market. Through the acquisition of these products, OcuMension expects to be capable of providing more comprehensive and advanced treatment solutions, further meeting patient needs and expanding market share. The Parties expect that the framework of this agreement will allow both Parties to further promote technological advancements and innovations in the field of ophthalmology. Ophthalmic diseases are internationally recognized as one of the highly focused medical sub-sectors, with innovative treatment solutions for ophthalmology still awaiting development. Based on this, OcuMension will continue to focus on bringing safer, more efficient, and cutting-edge treatment solutions to global ophthalmic patients, meeting the growing medical needs of patients. About Alcon Alcon helps people see brilliantly. As the global leader in eye care with a heritage spanning over 75 years, Alcon offers the broadest portfolio of products to enhance sight and improve people's lives. Alcon's Surgical and Vision Care products touch the lives of more than 260 million people in over 140 countries each year living with conditions like cataracts, glaucoma, retinal diseases and refractive errors. Alcon's more than 25,000 associates are enhancing the quality of life through innovative products, partnerships with Eye Care Professionals and programs that advance access to quality eye care. Learn more at . About OcuMension OcuMension is a China-based ophthalmic pharmaceutical platform company dedicated to identifying, developing and commercializing first- or best-in-class ophthalmic therapies. OcuMension's vision is to provide a world-class pharmaceutical total solution to address significant unmet ophthalmic medical needs in China. Since its inception, OcuMension has focused on building a platform integrating specialized capabilities in each major functionality involved in an ophthalmic drug's development cycle, from research and development, manufacturing to commercialization. OcuMension believes its platform positions it well to achieve leadership in China ophthalmology, with a first-mover advantage over future competitors. Advisors Morrison Foerster acted as legal advisor to OcuMension in this transaction. Lazard acted as financial advisor to Alcon and Gibson Dunn as its legal advisor. SOURCE OcuMension

AcquisitionLicense out/in

01 Mar 2024

·www.biospace.com

Palatin’s Dry Eye Drug Candidate Flops in Phase III Trial

Pictured: A close-up image of a red, irritated dry eye/courtesy of Kryuchka Yaroslav/Adobe Stock New Jersey-based Palatin Technologies announced Wednesday that the results for its dry eye disease candidate, PL9643, did not reach some of its primary and secondary endpoints in a pivotal late-stage study. The Phase III Melody-1 trial, evaluating the safety and efficacy of the melanocortin agonist PL9643, had two primary endpoints—one clinical symptom, pain, and one clinical sign, conjunctival lissamine green standing—along with other secondary endpoints. Palatin said that the candidate showed statistically significant results for the pain endpoint, with a p-value of <0.025. However, Palatin noted “positive treatment effects over the vehicle” with the intent to treat the population. Still, no statistical significance was found for the co-primary sign endpoint and secondary sign endpoints. The co-primary and secondary endpoints did not reach statistical significance in the unadjusted planned analyses. No exact details were provided for these results. “It is important to note that it is rare for one clinical study in DED to show efficacy for both a sign and a symptom. While additional analyses are ongoing, the initial results reinforce the potential of PL9643 as a treatment to address symptoms and signs of DED,” Palatin CEO Carl Spana said in a statement. “Our comprehensive data analysis is ongoing, and upon completion, we plan to meet with the FDA to discuss and get feedback on the design of the next pivotal Phase 3 clinical trial. Furthermore, we will continue our efforts to find a collaboration partner for our DED program,” Spana added. Palatin still touted the drug, stating that it was “clinically meaningful and statistically significantly effective” on an intent-to-treat basis, having reduced some symptoms, and overall the company was “pleased” that the candidate had favorable safety and tolerability data. According to the company, the remainder of the Phase III study, the efficacy, and the open label studies will start enrolling patients sometime in the second half of 2024. Palatin is facing competition in the dry eye space from Alcon which posted positive top-line results from two clinical trials in January 2024, showing its candidate AR-15512 had improved tear production. In May of last year, the FDA approved Bausch + Lomb and Novaliq’s perfluorohexyloctane ophthalmic solution, known as Miebo, to treat the symptoms of dry eye disease—specifically tear evaporation. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

Clinical ResultPhase 3Drug Approval

10 Jan 2024

·www.fiercebiotech.com

Alcon’s dry eye ambitions take off as $770M Aerie takeover delivers phase 3 wins

Alcon says dry eye affects an estimated 38 million people in the U.S. Alcon’s $770 million takeover of Aerie Pharmaceuticals has delivered an early win. The lead candidate in the acquired pipeline met the primary endpoint in a pair of phase 3 dry eye trials, positioning Alcon to file for FDA approval in the middle of the year. The studies randomized around 930 people with dry eye to receive AR-15512, a topical transient TRPM8 agonist, or vehicle control. After 14 days, a higher proportion of patients on AR-15512 had a 10 mm or greater increase in tear production, causing the program to meet its primary endpoint with a p value of less than 0.0001. Alcon saw improvements in tear production as early as day one. The effects persisted through to day 90, although the former Novartis unit is yet to share data from the trial. Alcon is also yet to comment on the phase 3 trial’s other secondary endpoints such as ocular discomfort, which was once a focus of AR-15512 development. AR-15512 failed to improve tear production or ocular discomfort on day 28 in an earlier study, causing that trial to miss its co-primary endpoints. Aerie looked past the setback, focused on successes against secondary goals—including tear production at day 14—designed a phase 3 program around the lessons of the earlier trial and was rewarded with a buyout bid from Alcon, plus positive top-line phase 3 data. Alcon plans to use the data, which is free from serious ocular adverse events, to file for FDA approval in the middle of 2024. Talking to investors on a quarterly results conference call in November, Alcon CEO David Endicott said it would “probably take four months, five months to get [the data] into a submission format.” The eye care specialist is also working to wrap up a long-term safety study by April. Approval will position Alcon to start selling a first-in-class treatment for dry eye disease, a condition that the company says affects an estimated 38 million people in the U.S. Around 20 million of those people are undiagnosed, according to Alcon, and fewer than 10% of people with a diagnosis take a prescription drug. Most patients initially try artificial tears, and most pharmacologic topical therapies, including Bausch + Lomb’s Xiidra, target inflammation. AR-15512 has a different mechanism, as researchers have tied TRPM8 to the detection of ocular surface dryness.

Phase 3Clinical ResultAcquisition

100 Deals associated with Acoltremon

External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Dry Eye Syndromes	Phase 3	US	Aerie Pharmaceuticals, Inc.	09 May 2022

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05285644 (COMET-2, Corporate Publications) Manual	Phase 3	Dry Eye Syndromes	-	AR-15512	(rykzuxitmm): P-Value = <0.0001 Met	Positive	09 Jan 2024
				Vehicle
NCT05360966 (COMET-3, Corporate Publications) Manual	Phase 3	Dry Eye Syndromes	-	AR-15512	(vcgcbemaeb): P-Value = <0.0001 Met	Positive	09 Jan 2024
				Vehicle
ARVO2023	Phase 3	Dry Eye Syndromes	-	AR-15512	zftfpoqdji(bjexlcustt) = kkzzlxnqsj igbnvbonbs (euaqnvrwke )	-	23 Apr 2023
				icilin	zftfpoqdji(bjexlcustt) = udxbyguwom igbnvbonbs (euaqnvrwke )

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