Methods of treating ocular neovascular diseases using AAV2 variants encoding aflibercept

A new blood vessel, disease technology used in the treatment of ocular neovascular diseases using AAV2 variants encoding aflibercept to address vision loss, increased intraocular pressure, retinal detachment, etc.

Pending Publication Date: 2022-04-19
ADVERUM BIOTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Adherence to such regimens is onerous for patients, their caregivers, and healthcare systems, and most patients fail to adhere to optimal therapy over time, which is associated with vision loss (Khanani AM, et al.)
In addition, there are complications including endophthalmitis, retinal detachment, traumatic cataract, and increased intraocular pressure (IOP); the risk of these complications may increase with repeated IVT injections (Falavarjani et al., (2013) Eye (Lond), 27(7):787-794)

Method used

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  • Methods of treating ocular neovascular diseases using AAV2 variants encoding aflibercept
  • Methods of treating ocular neovascular diseases using AAV2 variants encoding aflibercept
  • Methods of treating ocular neovascular diseases using AAV2 variants encoding aflibercept

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0326] Example 1: In 6×10 11 An open-label phase 1 study of AAV2.7m8-aflibercept in neovascular (wet) age-related macular degeneration at vg / eye dose

[0327] This example describes the use of AAV2.7m8-aflibercept, an rAAV vector containing the VEGF inhibitor aflibercept and the AAV2.7m8 protein capsid, for the treatment of age-related macular degeneration (AMD) with choroidal neovascularization ) (wet AMD; wAMD) open-label phase 1 study.

[0328] I. Purpose of the study

[0329] A. Main purpose

[0330] The primary objective of this study was to evaluate the safety and tolerability of a single intravitreal (IVT) injection of AAV2.7m8-aflibercept in subjects with wAMD.

[0331] primary endpoint

[0332] The primary endpoint of the study was the type, severity and incidence of ocular and systemic adverse events (AEs).

[0333] B. Secondary purpose

[0334] The secondary objectives of these studies are to:

[0335] · To evaluate the effect of AAV2.7m8-aflibercept o...

Embodiment 2

[0552] Example 2: In Neovascular (Wet) Age-Related Macular Degeneration Below 6×10 11 Dose vg / eye and open-label phase 1 study of AAV2.7m8-aflibercept with topical corticosteroids

[0553] The following examples describe a continuation of the Phase 1 study described in Example 1 to evaluate 11 Dose of vg / eye and safety and efficacy of AAV2.7m8-aflibercept administered with topical corticosteroids in subjects with wAMD.

[0554] I. Study Objectives and Endpoints

[0555] The primary objective, secondary objectives and primary and secondary endpoints are as described in Example 1, Part I.

[0556] II. Research object

[0557] The subjects of this study were as described in Example 1, Part II. III. Investigational Drugs

[0558] The study drug was AAV2.7m8-aflibercept as described in detail in Part III of Example 1 and as Figure 1A , except that the concentration of AAV2.7m8-aflibercept was varied in order to maintain an appropriate injection volume, as described in...

Embodiment 3

[0621] Example 3: In neovascular (wet) age-related macular degeneration, below 6×10 11 Results of an open-label phase 1 study of AAV2.7m8-aflibercept at a dose of vg / eye with topical corticosteroids

[0622] This example describes the results of the Phase 1 study described in Example 2, which evaluated subjects with wAMD at less than 6×10 11 Dose of vg / eye and safety and efficacy of AAV2.7m8-aflibercept administered with topical corticosteroids.

[0623] result

[0624] group 2

[0625] The baseline characteristics of the subjects in Cohort 2 are provided in Table 13.

[0626] Table 13. Baseline Characteristics of Subjects in Cohort 2

[0627]

[0628] As described in Example 2, subjects in cohort 2 received a 2×10 11 Dose 2 of vg / eye administered a single IVT injection of AAV2.7m8-aflibercept with 60 mg of prednisone starting 3 days before and 3 days after AAV2.7m8-aflibercept treatment for 6 days. This was followed by a 7-day prednisone taper. A summary of the...

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PUM

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Abstract

Provided are methods for treating ocular neovascular disease in an individual comprising administering to one eye of the individual a unit dose of a recombinant adeno-associated virus (rAAV) particle wherein the rAAV particle comprises: a) a nucleic acid encoding a polypeptide and flanking an AAV2 inverted terminal repeat (ITR), the present invention relates to a polypeptide comprising an amino acid sequence having at least about 95% identity to the amino acid sequence of SEQ ID NO: (35), and b) an AAV2 capsid protein comprising the amino acid sequence LGETTRP (SEQ ID NO: (14)) interposed between positions (587) and (588) of the capsid protein wherein the amino acid residue number corresponds to the AAV2VP1 capsid protein.

Description

[0001] Cross References to Related Applications [0002] This application claims U.S. Provisional Patent Application No. 62 / 899,070 filed September 11, 2019, U.S. Provisional Patent Application No. 62 / 913,648 filed October 10, 2019, International Application No. PCT / US2019 / 062066, U.S. Provisional Patent Application No. 62 / 959,784, filed January 10, 2020, U.S. Provisional Patent Application No. 62 / 971,835, filed February 7, 2020, U.S. Provisional Patent Application No., filed May 1, 2020 63 / 019,190, U.S. Provisional Patent Application No. 63 / 030,819, filed May 27, 2020, and U.S. Provisional Patent Application No. 63 / 063,203, filed Aug. 7, 2020, the disclosures of which are hereby incorporated by reference in their entirety Incorporated into this article. technical field [0003] The present disclosure relates to methods of treating ocular neovascular diseases and disorders in an individual comprising administering to the eye of the individual a single unit dose of a recombin...

Claims

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Application Information

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IPC IPC(8): A61K35/761A61K38/16A61K38/17A61K31/713A61K45/06C12N7/00C12N15/86A61P27/02A61K31/573
CPCA61K31/573A61K31/713A61K35/761A61K38/162A61K38/179A61K45/06A61K9/0048A61P27/02C12N7/00C12N15/86C12N2750/14122C12N2750/14133C12N2750/14143A61K2300/00A61K47/02A61K47/10A61K31/575A61K48/005A61K48/0075C07K14/71C12N2710/14144
Inventor M·盖斯米S·基斯A·奥斯本A·特普库
Owner ADVERUM BIOTECH INC
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