Atorvastatin

Atorvastatin is multi-modal in its mechanism of action with  the potential to treat both evaporative and aqueous deficient forms of the disease. In a recent pilot study of 10 patients with blepharitis and dry eye, which often co-exist,  positive results with reduced corneal fluorescein staining and conjunctival redness, improved tear break-up times (TBUT) and normalised Schirmer’s wetting was recorded. There was improved blepharitis, as well as dry eye symptom scores. It is non-steroidal with no steroid-like related side effects. 

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Preclinical data showed that, when Lacripep was added topically in animal models, it restored basal tearing without irritation and healed the corneal surface of the eye. TearSolutions has now completed a first-in-human Phase I/II trial in primary Sjögren’s Syndrome, who typically have a severe and often debilitating form of ocular surface disease and are known to be deficient in Lacritin.  The results showed a rapid improvement, as quickly as two weeks, in corneal health and a reduction in symptoms. 

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By inhibiting RASP, which are elevated in a variety of inflammatory diseases, reproxalap represents a novel mechanism for diminishing ocular inflammation in dry eye disease. In a number of clinical trials, reproxalap demonstrated consistent statistically significant and clinically relevant activity. Topical ocular reproxalap is an investigational new drug candidate that has been studied in more than 1,800 patients with no observed safety concerns; mild and transient instillation site discomfort is the most commonly reported adverse event in clinical trials. 

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Lubricin functions like biologic Teflon®. It is naturally produced throughout the human body protecting tissues and other surfaces from friction-related damage and wear. Lubricin is the most lubricating and anti-adhesive molecule in the human body and has natural anti-inflammatory properties as well.  Originally identified in joints, lubricin is also found on the ocular surface and in numerous additional tissues throughout the human body. Supplementation with recombinant human lubricin is an innovative and exciting new approach to disease management.

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AZR-MD-001 harnesses the power of selenium sulfide in an easy-to-use ophthalmic ointment preparation applied directly to the meibomian glands in the lower eyelid. AZR-MD-001 is thought to have a multi-modal mechanism of action that treats the pathophysiology of MGD along with the resulting ocular surface symptoms. AZR-MD-001’s formulation targets the main pathophysiology of abnormal keratin production, keratin obstruction, poor meibum quality, and resulting ocular signs and symptoms through a variety of ways.

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Currently recruiting for clinical trials.

Branches of the trigeminal nerve innervating the cornea and lids selectively express cold-sensitive thermoreceptors, called transient receptor potential melastatin 8 (TRPM8) receptors. TRPM8 receptors are associated with the detection of ocular surface dryness and are activated by evaporative cooling and hyperosmolarity, leading to stimulation of tear production. In addition, agonists of TRPM8 promote a cooling sensation that may be beneficial for reducing ocular discomfort and pain. Thus, TRPM8 agonists such as AR-15512, may have a dual role in the potential treatment of DED by both stimulating tear production and reducing ocular discomfort.

Tivanisiran is a small interfering RNA (siRNA) that is administers as eye drops. It is currently in Phase III clinical research - it inhibits TRPV1. TRPV1 is directly involved in the pathophysiology of dry eye disease as it has a dual function on the ocular surface. It acts in the detection, transmission and regulation of pain in the eye, as well as in the mediation of innate inflammatory response mechanisms whose regulation is key for the treatment and prevention of dry eye disease. 

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Lotilaner, the active ingredient in XDEMVY, is designed to target and eradicate Demodex mites, which have been implicated in MGD. XDEMVY acts specifically via mite GABA-gated chloride channels to target, paralyze, and kill Demodex mites. XDEMVY is currently in phase 2 development and being investigated as a potential treatment for MGD. If approved, XDEMVY may potentially become the first FDA-approved therapy and definitive standard of care for millions of people struggling with the effects of MGD.

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SYK is a protein kinase that relays immune receptor signalling within a cell. It transmits signals from a variety of cell surface receptors and sends signals throughout a cell in order to trigger an immune response if needed. SYK is the critical starting point in the activation of the inflammatory/immune cascade. Inhibition of the SYK can cause a broad anti-inflammatory effect. Dual ENKephalinase Inhibitors (DENKIs), inhibit the two enkephalin-degrading enzymes in order to enhance the body’s natural pain management system. This means DENKI can provide an alternative, non-addictive, safe, and effective treatment option for pain management.

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PolyCol’s ability to rapidly repair the damaged collagen present in dry eye disease, coupled with the concurrent recovery of the corneal epithelium, corneal nerves and reduction of inflammation, make this the company’s initial focus through the drug candidate ST-100 (vezocolmitide). The development of ST-100 is supported by compelling animal testing results, with complete healing of damaged corneal tissues in 24 hours or less, and full recovery of damaged corneal and trigeminal nerve structures, including goblet cells and corneal epithelium.

Palatin is developing a truly novel class of drugs that selectively bind to melanocortin receptors (MCR), with both MCR1 and pan-agonists, to directly activate natural pathways that resolve disease inflammation in the eye. Melanocortin agonists provide potential advantages over current options to better meet the needs of patients and clinicians by directly addressing harmful inflammation, resulting in rapid, global improvement of affected tissues. PL9643 ophthalmic solution  is currently undergoing late-stage Phase 3 clinical development which demonstrated improvements in both the signs and symptoms of DED after just 2 weeks of treatment, with no safety signals and excellent tolerability.

The Redwood Pharma product under development will be the first to target the basic biological mechanism related to local estrogen deficiency. As the amount of circulating systemic estrogen can drop by over 90% when women go through menopause, vital tissues dry up and cause problems for patients.  RP101 will deliver a low-dose of the active substance topically to the eye to help reduce DED symptoms.  RP101 has demonstrated safety and efficacy across a wide variety of measures in a European Phase II clinical trial. This study confirmed results from two prior Phase II clinical trials in the US. Read More.

OK-101 is a novel class of chemerin receptor agonist that produces an anti-inflammatory action and reduction in neuropathic pain. Inclusion of a lipid ‘anchor’ within the OK-101 drug molecule is designed to decrease washout due to tearing and blinking, and to enhance the ocular residence time of OK-101.

Protearin™ is based on the glycoprotein clusterin, a natural, protective component of fluid-tissue interfaces throughout the body. Protearin™ targets the final common end point for all forms of dry eye, i.e., damage at the ocular surface and disruption of the ocular surface barrier. Preclinical testing and results of Protearin™ make a strong case to use clusterin as a biological drug to prevent or treat not only dry eye but also other corneal disorders involving damage to the ocular surface barrier.  No drugs are currently on the market to address ocular surface barrier disruption.

NRO-1 is a topically delivered, nerve regenerative therapeutic that accelerates nerve regeneration and recovery of functional nerves. It is a GDNF releasing small molecule that ameliorates corneal epithelial layer and it is positioned to initiate P2a trial for neurotrophic keratitis patients.  

The compound, named OCS-02, is based on a proprietary single-chain antibody fragment technology specifically designed for topical delivery. Efficacy and safety were evaluated in three clinical trials including two controlled studies under IND. The studies demonstrated a promising profile for treating inflammatory conditions of the anterior segment of the eye including dry eye disease.

As an integrin alpha-4 antagonist, AXR-159 is a first-in-class therapeutic with steroid-like efficacy in preclinical models targeting a novel mechanism in the eye for the chronic treatment of DED. AXR-159 has been tested extensively in preclinical models of efficacy and safety and has successfully completed a Phase 2 clinical proof-of-concept study.

The content here is for informational and educational purposes only. It is not intended for medical advice. It does not take the place of a medical advice or treatment from a physician. Readers should consult their own doctor or a qualified healthcare professional for specific health concerns and questions.