Ethylene Vinyl Acetate Implant (VitalDose®)

Sponsor(s)

No sponsor indicated

Partnerships

	Population Council https://popcouncil.org/
	Bachem, ltd https://www.bachem.com/
	Nanoform Finland Ltd https://nanoform.com/en/
	Glaukos Corporation https://www.glaukos.com/en-uk/
	Alessa Therapeutics, Ltd https://alessatherapeutics.com/
	John Hopkins University https://www.jhu.edu/
	The Gates Foundation https://www.gatesfoundation.org/

Type of technology

Polymeric implant

Administration route

Intratumoral, ocular insert, intrathecal, Subcutaneous, Intra-vitreal, Topical (Vaginal), Transdermal

Development state and regulatory approval

travoprost

Marketed

Approved by USFDA on 14 December 2023 for open-angle glaucoma (OAG) or ocular hypertension (OHT)

Description

VitalDose is a polymer-based microporous long-acting implant for systemic and local drug delivery. It has a high drug-loading capacity and supports small molecules, peptides, monoclonal antibodies, and iRNA therapeutics. The implant maintains plasma concentrations for months to years, depending on the API’s pharmacokinetics. Available in rod, ring, and film configurations, it enables versatile clinical applications.

Technology highlight

1) Contraceptive Sustained Release implant (6 months-5 years) 2) Biodurable design made using hydrophobic polymer 3) Customizable design 4) <70% API loading 5) Zero Order Kinetics 6) Refillable, replaced and retrieved 7) Low off-targeting toxicities 8) 40% vinyl acetate serves as a drug matrix while 18% vinyl acetate forms the rate control membrane

Technology main components

1. Polymer Matrix (30–100 wt%) – Core polymers include poly(lactic-co-glycolic acid), polyolefins, polyvinyl chloride, polycarbonates, polysulfones, styrene-acrylonitrile copolymers, polyurethanes, silicone polyether-urethanes, polycarbonate urethanes, and silicone polycarbonate-urethanes. Example: Ateva 4030AC. 2. Excipients—Radiocontrast agents, hydrophilic compounds, bulking agents, plasticizers, surfactants, crosslinking agents, flow aids, colorizing agents (e.g., chlorophyll, methylene blue), antioxidants, stabilizers, lubricants, antimicrobial agents, and preservatives. 3. Surfactants—One or more nonionic, anionic, and/or amphoteric surfactants. 4. API—Small molecules, proteins, or iRNA therapeutics. 5. Bromelain Powder

Information on the raw materials sourcing, availability and anticipated price

iDose TR 75 mcg intraocular implant is around 13,950 USD/implant

Delivery device(s)

Sterile single-dose Implant inserter

API desired features

Water-soluble molecules

Water-insoluble molecules

Small molecules

VitalDose EVA implants target specific pharmacological classes, including estrogen hormones, tetracycline antibiotics, and antiviral agents. The platform primarily delivers small molecules acting as allosteric agonists or inhibitors. Therapeutic agents that are used for treating solid tumor, ocular inflammation, glaucoma, psychiatric disorders, and osteoporosis are also targeted for VitalDose EVA implant.

Nucleic acids

Suitable vaccines include whole viral particles, recombinant proteins, subunit proteins (gp41, gp120, gp140), DNA vaccines, plasmids, bacterial vaccines, and polysaccharides such as extracellular capsular polysaccharides, along with other vaccine vectors. Similarly, nucleic acids may include RNA- or DNA-based molecules such as oligonucleotides, aptamers, ribozymes, DNAzymes, and small interfering RNAs (siRNA), including messenger (mRNA), transfer (tRNA), ribosomal (rRNA), and interfering (iRNA) RNAs.

Proteins

Suitable proteins or peptides may include adrenocorticotropic hormone, angiotensin, β-endorphin, bombesin, calcitonin, calcitonin gene-related polypeptide, cholecystokinin-8, colony-stimulating factors, desmopressin, endothelin, enkephalin, erythropoietins, gastrins, glucagon, human atrial natriuretic polypeptide, interferons, insulin, growth factors, growth hormones, luteinizing hormone-releasing hormone, melanocyte-stimulating hormone, muramyl-dipeptide, neurotensin, oxytocin, parathyroid hormone, peptide T, secretin, and somatomedins.

Additional solubility data

Not provided

Additional stability data

Not provided

API loading: Maximum drug quantity to be loaded

50-75 wt%

API co-administration

2 different APIs : Not provided

LogP

Min: -6.9 Max: 5

Scale-up prospects

Celanese produces 60,000 metric tons of vinyl acetate annually at its Nanjing facility and plans to expand production by 10,000 metric tons per year. Additionally, Celanese and Nanoform are collaborating to enhance biologics delivery through small implants using the VitalDose platform. Meanwhile, Celanese and Glaat Pharmaceuticals have partnered on formulation development and and clinical trial setup.

Tentative equipment list for manufacturing

HAAKE™ Rheomix OS Mixers

Manufacturing

Manufacturing Process of EVA Implants (Hot Melt Extrusion(HME) /Fusion Deposition 3D Modeling) i) Mixing Processes (One or more of the following) 1. Melt mixing 2. Extrusion 3. Batch mixing 4. Roll milling ii) Melt Processing Techniques at 210°C (One or more of the following) 1. Compression molding 2. Injection molding (injection phase and holding phase) 3. Blow molding 4. Vacuum forming 5. Calendaring 6. Extrusion 7. Spinning 9. Film formation The API and ground EVA polymer are dry blended and are fed into HME to yield the final product form.

Specific analytical instrument required for characterization of formulation

UV/Vis absorption spectroscopy using Cary 1 split beam instrument

GC-010

Identifier

NCT03519386

Link

https://clinicaltrials.gov/study/NCT03519386

Phase

Phase III

Status

Completed

Sponsor

Glaukos Corporation

More details

Phase III study to compare the safety and efficacy of intraocular implants containing travoprost at two different elution rates versus Timolol Maleate Ophthalmic Solution, 0.5% (timolol) in reducing elevated intraocular pressure in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Purpose

Randomized Study Comparing Two Models of a Travoprost Intraocular Implant to Timolol Maleate Ophthalmic Solution, 0.5%

Interventions

Intervention 1

Potential application(s)

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2018-07-26

Anticipated Date of Last Follow-up
2024-11-12

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2022-04-05

Actual Completion Date
2024-04-02

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: * Diagnosed with open-angle glaucoma or ocular hypertension. * C/D ratio ≤ 0.8 * Zero to three preoperative ocular hypotensive medications Exclusion Criteria: * Active corneal inflammation or edema. * Retinal disorders not associated with glaucoma.

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

590

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

IDOS-402-IVIV

Identifier

NCT06582732

Link

https://clinicaltrials.gov/study/NCT06582732

Phase

Phase II

Status

Completed

Sponsor

Glaukos Corporation

More details

To evaluate the performance of the Travoprost Intracameral Implant by determining residual drug in explanted implants of the Travoprost Intracameral Implant and by determining aqueous humor concentrations of travoprost free acid at specified timepoints post administration through 24 months

Purpose

Performance of the Travoprost Intraocular Implant

Interventions

Intervention 1

Potential application(s)

Intervention 2

Potential application(s)

Intervention 3

Potential application(s)

Intervention 4

Potential application(s)

Intervention 5

Potential application(s)

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2021-03-10

Anticipated Date of Last Follow-up
2024-09-19

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2023-11-02

Actual Completion Date
2023-11-02

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: * Diagnosis of either open angle glaucoma (i.e. primary, pseudoexfoliation, or pigmentary glaucoma) or ocular hypertenson * Zero to three topical intraocular pressure lowering medications at the time of Visit 1 (Screening) exam. * Best spectacle corrected visual acuity of 16 letters or more correctly read at 4 meters or better in each eye. * Open angle as defined by Shaffer grade ≥ 3 at slit-lamp at the planned implantation site Exclusion Criteria: * Traumatic, uveitic, neovascular, or angle-closure glaucoma; or glaucoma associated with vascular disorders * Active ocular inflammation, infection or edema * Clinically significant dystrophy (e.g., bullous keratopathy, Fuch's dystrophy) or clinically significant guttata

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

210

Allocation

Not provided

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

Proprietary excipients used

No proprietary excipient used

Novel excipients or existing excipients at a concentration above Inactive Ingredients Database (IID) for the specified route of administration

No novel excipient or existing excipient used

Residual solvents used

No residual solvent used

Other features of the technology

• Biodegradable
• Monolithic

Release properties

VitalDose is a continuous drug delivery system that releases therapeutic agents from an ethylene vinyl acetate (EVA) membrane at a steady, low-dose rate, with sustained release lasting up to three years. In intratumoral administration, the drug exhibits modified kinetics, allowing for a gradual and controlled release directly into the tumor microenvironment, optimizing therapeutic efficacy while minimizing systemic exposure.

Injectability

VitalDose is a liquid formulation and can be injected using a standard injection device with a standard 21-25 gauge needle or even thinner depending on the formulation characteristics.

Safety

In the Phase 3 clinical trial of iDose, the Travoprost VitalDose implant was evaluated for safety. Among the patients who received the implant, 2.6% experienced systemic serious adverse events (SAEs), while 0.5% experienced ocular SAEs. The most common side effects were iritis, ocular hyperemia, reduced visual acuity, and increased intraocular pressure (IOP).

Stability

The API in the EVA implant demonstrated stability over a period of 6 months.

Storage conditions and cold-chain related features

Store at 2°C to 25°C (36°F to 77°F). Do not freeze

Therapeutic area(s)

Use case(s)

Use of technology

Description

Implantable Device for Sustained Release of a Macromolecular Drug Compound

Brief description

An implantable device for delivery of a macromolecular drug compound is provided. The device comprises a core having an outer surface and a membrane layer positioned adjacent to the outer surface of the core. The core comprises a core polymer matrix within which is dispersed a drug compound having a molecular weight of about 0.5 kDa or more, the polymer matrix containing a hydrophobic polymer. Further, the membrane layer comprises a membrane polymer matrix within which the macromolecular drug compound is optionally dispersed. The concentration of the macromolecular drug compound in the core is greater than the concentration of the macromolecular drug compound in the membrane layer.

Representative patent

US20190358167A1

Category

Device

Patent holder

Celanese EVA Performance Polymers Corporation

Exclusivity

Not provided

Expiration date

May 20, 2039

Status

Active

Description

Injection Molded Medical Devices Made From A High Molecular Weight Polyethylene

Brief description

A high molecular weight polyethylene polymer is formulated so that the polymer is capable of being injection molded. The polyethylene polymer has a Viscosity Number of greater than about 400 ml/g and has a melt flow rate of greater than about 0.9 g/10 min. The polyethylene polymer is of high purity and is particularly well suited for producing medical products.

Representative patent

US20240262942A1

Category

Device

Patent holder

Celanese International Corp

Exclusivity

Not provided

Expiration date

Not provided

Status

Pending

Publications

There are no publication

Additional documents

• VITALDOSE Published Report

• LEAP Workshop Summary

Useful links

There are no additional links

	Collaborate for development Consider on a case by case basis, collaborating on developing long acting products with potential significant public health impact, especially for low- and middle-income countries (LMICs), utilising the referred to long-acting technology Not provided
	Share technical information for match-making assessment Provide necessary technical information to a potential partner, under confidentiality agreement, to enable preliminary assessment of whether specific medicines of public health importance in LMICs might be compatible with the referred to long-acting technology to achieve a public health benefit Not provided
	Work with MPP to expand access in LMICs In the event that a product using the referred to long-acting technology is successfully developed, the technology IP holder(s) will work with the Medicines Patent Pool towards putting in place the most appropriate strategy for timely and affordable access in low and middle-income countries, including through licensing Not provided