Search

US-20260124189-A1 - METHODS AND DEVICES FOR THE TREATMENT OF OCULAR DISEASES IN HUMAN SUBJECTS

US20260124189A1US 20260124189 A1US20260124189 A1US 20260124189A1US-20260124189-A1

Abstract

Methods and devices are provided for targeted non-surgical administration of a drug formulation to the suprachoroidal space (SCS) of the eye of a human subject for the treatment of a posterior ocular disorder or a choroidal malady. In one embodiment, the method comprises inserting a hollow microneedle into the eye at an insertion site and infusing a drug formulation through the inserted microneedle and into the suprachoroidal space of the eye, wherein the infused drug formulation flows within the suprachoroidal space away from the insertion site during the infusion. In one embodiment, the fluid drug formulation comprises drug nanoparticles or microparticles.

Inventors

  • Vladimir ZARNITSYN
  • Samirkumar Patel
  • Daniel White
  • Glenn Noronha
  • Brian Burke

Assignees

  • CLEARSIDE BIOMEDICAL, INC.

Dates

Publication Date
20260507
Application Date
20250603

Claims (20)

  1. 1 . A method of treating a posterior ocular disorder in a human subject in need thereof, the method comprising, non-surgically administering an effective amount of a drug formulation to the suprachoroiclal space (SCS) of the eye of the human subject in need of treatment of the posterior ocular disorder, wherein upon administration, the drug formulation flows away from the insertion site and is substantially localized to the posterior segment of the eye.
  2. 2 . The method of claim 1 , wherein the administering step comprises inserting a hollow microneedle into the sclera at an insertion site, the microneedle having a tip end with an opening and infusing the drug formulation into the SCS through the inserted microneedle.
  3. 3 . The method of claim 2 , wherein the insertion site is at about the equator of the eye, or between the equator and the limbus of the eye.
  4. 4 . The method of claim 2 , wherein the microneedle has a length of from about, 500 μm and about 1500 μm.
  5. 5 . The method of claim 2 , wherein the microneedle has a diameter of from about 200 μm to about 600 μm.
  6. 6 . The method of claim 2 , wherein the microneedle has a bevel angle of about 5 degrees to about 30 degrees.
  7. 7 . The method of claim 2 , wherein the bevel height is from about 100 μm to about 500 μm.
  8. 8 . The method of claim 2 , wherein the microneedle is inserted into the sclera without penetrating through the sclera.
  9. 9 . The method of claim 2 , wherein the microneedle is inserted into the sclera without penetrating through the choroid.
  10. 10 . The method of claim 2 , wherein the microneedle comprises a beveled tip.
  11. 11 . The method of claim 10 , wherein the beveled tip has an angle from about 10 degrees to about 20 degrees.
  12. 12 . The method of claim 10 , wherein the beveled tip has an aspect ratio of from about 1:1.5 to about 1:10.
  13. 13 . The method of claim 10 , wherein the beveled tip has a height of from about 500 μm to about 1 mm.
  14. 14 . The method of claim 2 , wherein the microneedle has a length of from about 500 μm to about 1500 μm.
  15. 15 . The method of claim 14 , wherein the microneedle has a length of from about 500 μm to about 1000 μm.
  16. 16 . The method of claim 2 , wherein the microneedle comprises a cylindrical shaft having an outer diameter of from about 200 microns to about 600 microns.
  17. 17 . The method of claim 1 , wherein the effective amount of the drug formulation is present in a volume of from about 10 μL to about 200 μL.
  18. 18 . The method of claim 1 , wherein the effective amount of the drug formulation is present in a volume of from about 30 μL to about 100 μL.
  19. 19 - 108 . (canceled)
  20. 109 . A method for treating a choroidal malady in a human patient, the method comprising: non-surgically administering a drug formulation comprising an effective amount of an anti-inflammatory drug, a vascular endothelial growth factor (VEGF) modulator, a platelet derived growth factor (PDGF) modulator, an angiogenesis inhibitor, an immunosuppressive agent, a vascular permeability inhibitor, or a combination thereof, to the suprachoroidal space (SCS) of the eye of the patient.

Description

CROSS REFERENCE TO RELATED APPLICATIONS This Application is a division of U.S. Utility application Ser. No. 17/314,272, filed May 7, 2021, which is a continuation of U.S. Utility application Ser. No. 16/737,010, filed Jan. 8, 2020, now abandoned, which is a continuation of U.S. Utility application Ser. No. 16/124,407, filed Sep. 7, 2018, now abandoned, which is a continuation of U.S. Utility application Ser. No. 15/454,636, filed Mar. 9, 2017, now abandoned, which is a continuation of U.S. Utility application Ser. No. 14/441,151, filed May 6, 2015, now abandoned, which is a U.S. National Phase of PCT/US2013/069156, filed Nov. 8, 2013, which claims priority from U.S. Provisional Application Ser. Nos. 61/724,144, filed Nov. 8, 2012; 61/734,872, filed Dec. 7, 2012; 61/745,237, filed Dec. 21, 2012; 61/773,124, filed Mar. 5, 2013; 61/785,229, filed Mar. 14, 2013; 61/819,388, filed May 3, 2013; 61/873,660, filed Sep. 4, 2013, and 61/898,926, filed Nov. 1, 2013, all of which are incorporated herein by reference in their entireties for all purposes. BACKGROUND OF THE INVENTION This invention is generally in the field of ophthalmic therapies, and more particularly to the use of a microneedle for infusion of a fluid drug formulation into ocular tissues for targeted, local drug delivery. The delivery of drug to the eye is extremely difficult, particularly delivery of macromolecules and delivery to the posterior segment. Many inflammatory and proliferative diseases in the posterior region of the eye require long term pharmacological treatment. Examples of such diseases include macular degeneration, diabetic retinopathy, and uveitis. In addition, many choroidal maladies that are associated with inflammatory responses, proliferation, and neovascularization require long term pharmacological treatment. It is difficult to deliver effective doses of drug to the posterior segment using conventional delivery methods such as topical application, which has poor efficacy, and systemic administration, which often causes significant side effects, and often does not reach the site of infection. (Geroski & Edelhauser, Invest. Ophthalmol. Vis. Sci. 41:961-64 (2000)). For example, while eye drops are useful in treating conditions affecting the exterior surface of the eye or tissue(s) at the front of the eye, the eye drops cannot significantly penetrate the eye, as may be required for the treatment of various retinal diseases and choroidal maladies. Direct injection into the eye, using conventional needles and syringes has been reported to be effective, but requires professional training and raises concerns about safety (Maurice, J. Ocul. Pharmacol. Ther. 17:393-401 (2001)). It also would be desirable to be able to minimize the number and/or frequency of eye injection treatments needed to deliver therapeutically effective amounts of drug to the ocular tissue sites that need it. The suprachoroidal space (SCS) of the eye has been studied, and its cannulation described as a possible route for drug delivery. See, e.g., Olsen, et al., American J. Ophthalmology 142 (5): 777-87 (November 2006); PCT Patent Application Publication No. WO 2007/100745. It therefore would be desirable to provide better, safer, more effective techniques for the direct delivery of therapeutic agents to posterior segment eye tissues, for example, to treat a posterior ocular disorder. It further would be desirable to provide better, safer, more effective techniques for the direct delivery of therapeutic agents to the SCS for the treatment of choroidal maladies, for example, choroidal maladies associated with vascular abnormalities. The present invention addresses these and other needs. SUMMARY OF THE INVENTION In one aspect, the present invention relates to non-surgical ophthalmic therapies in human patients in need of such treatment, and more particularly to the infusion of a drug formulation into the suprachoroidal space of the eye for targeted, local drug delivery, for the treatment of posterior ocular disorders, choroidal maladies and other diseases associated with vascular abnormalities. In one aspect of the invention, a method is provided for treating a posterior ocular disorder in a human subject in need of treatment. In one embodiment, the method comprises non-surgically administering an effective amount of a drug formulation to the suprachoroidal space (SCS) of the eye of the subject in need of treatment of the posterior ocular disorder or choroidal malady. In a further embodiment, upon administration, the drug formulation flows away from the insertion site and is substantially localized to the posterior segment of the eye. In one embodiment, the posterior ocular disorder is an ocular inflammatory condition such as uveitis, scleritis, glaucoma, ocular sarcoidosis, optic neuritis, macular edema, diabetic retinopathy, macular degeneration, a corneal ulcer, an autoimmune disorder, ophthalmic manifestations of AIDS, optic nerve degeneration, geographic atrophy, ch