CEQUATM featuring innovative NCELLTM Technology1

Encapsulates. Penetrates. Delivers.1,2

Cyclosporine (CsA) has been used as an effective way to treat dry eye disease for many years. But due to its poor aqueous solubility, cyclosporine faces challenges in its delivery.3 CEQUA (cyclosporine ophthalmic solution) 0.09% is the first and only FDA-approved cyclosporine treatment delivered with NCELL Technology.1,4 NCELL Technology's innovative delivery system addresses these solubility challenges.1,3

Watch NCELL in Action

Transcript

((Voice-Over))

Welcome to CEQUA–an innovative cyclosporine formulation with advanced NCELL technology for dry eye disease.

What makes CEQUA different?

CEQUA is a clear, uncolored solution that offers the highest concentration of cyclosporine approved by the FDA (for ocular use). The proven cyclosporine molecule is delivered with advanced proprietary NCELL technology for increased ocular penetration. Specifically, CEQUA increases tear production.

The proven efficacy of cyclosporine

The cyclosporine molecule has been used as an effective treatment for dry eye for many years.

In patients with ocular inflammation due to dry eye, cyclosporine helps restore tear production by acting as a partial immunomodulator. The exact mechanism of action is not known.

However, delivering the cyclosporine molecule to the eye has been challenging due to its poor aqueous solubility. Different approaches have been used to help overcome the solubility issue and deliver the cyclosporine molecule into the eye.

The benefits of NCELL technology

NCELL helps address the solubility challenges of cyclosporine with an innovative delivery system.

NCELL technology uses nanomicelles composed of a blend of polymers including polyoxyethylene hydrogenated castor oil 40, or HCO-40, and Octoxynol-40, or Oc-40.

The units of polymers self-assemble into a nanoscale aggregate via a thermodynamic process.

Once assembled, the polymers work together as a unit, or nanomicelle, with a hydrophilic outer layer and hydrophobic core.

The hydrophilic outer layer, which is compatible with the aqueous environment of the tear film, allows for transport through the tear film onto the ocular surface. At the same time, the hydrophobic core prevents the encapsulated cyclosporine from being released until after the nanomicelle penetrates the aqueous layer of the tear film.

The small size of the nanomicelles, which measure an average of 22 nanometers or approximately one three-thousandth the width of a human hair, helps facilitate the entry of cyclosporine into corneal and conjunctival cells. The nanomicelles penetrate the aqueous layer of the tear film and release the active cyclosporine molecules for penetration into ocular tissues.

Once released, cyclosporine gets to work to reduce inflammation, helping improve the ocular surface and increase tear production.

Enhanced penetration of CEQUA

CEQUA helps ensure that more of the cyclosporine molecule gets where it is needed.

In a single-dose, preclinical study vs a cyclosporine emulsion, a cyclosporine formulation with NCELL enabled nearly 3 times more of the molecule to penetrate the cornea, while allowing 1.6 times more of the molecule to penetrate the conjunctiva.

CEQUA offers an innovative formulation of cyclosporine with NCELL, resulting in increased penetration and delivery of the proven anti-inflammatory power of cyclosporine.

Prescribe CEQUA today so your patients can experience the benefits of NCELL for dry eye.

Indications and Usage

CEQUA (cyclosporine ophthalmic solution) 0.09% is a calcineurin inhibitor immunosuppressant indicated to increase tear production in patients with keratoconjunctivitis sicca (dry eye).

Important Safety Information

Warnings and Precautions

Potential for Eye Injury and Contamination: To avoid the potential for eye injury and contamination, advise patients not to touch the vial tip to the eye or other surfaces.

Use with Contact Lenses: CEQUA should not be administered while wearing contact lenses. If contact lenses are worn, they should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following administration of CEQUA ophthalmic solution.

Adverse Reactions

The most common adverse reactions reported in greater than 5% of patients were pain on instillation of drops (22%) and conjunctival hyperemia (6%). Other adverse reactions reported in 1% to 5% of patients were blepharitis, eye irritation, headache, and urinary tract infection.

Please see the Full Prescribing Information.

MECHANISM OF DELIVERY

The nanomicelle is equipped for the journey

Delivering cyclosporine to ocular tissues, NCELL Technology encapsulates the cyclosporine, allowing it to penetrate the aqueous layer of the tear film.1,2

Image of polymers self-assembling into a hydrophobic core

NCELL Encapsulates

NCELL Technology uses nanomicelles composed of a blend of polymers.

These polymers self-assemble into the hydrophobic core protecting the cyclosporine so it isn’t released in the aqueous layer of the tear film.1,5

Image of a nanomicelle penetrating the aqueous layer of the tear film

NCELL Penetrates

The small size facilitates entry into corneal and conjunctival cells.

Nanomicelles are able to penetrate the aqueous layer of the tear film because of their hydrophilic outer layer.1,3,5

Image of the nanomicelle breaking up

NCELL Delivers

The nanomicelles then break up to release cyclosporine for penetration into ocular tissues.3,5

Once released, cyclosporine gets to work to reduce inflammation, helping improve the ocular surface and increase tear production.2,5

ANATOMY OF NCELL

Overcoming aqueous solubility

NCELL is engineered to address cyclosporine solubility challenges to better reach the ocular surface.1,3 By using a protective hydrophilic shell, NCELL Technology delivers encapsulated cyclosporine in a secured hydrophobic core to the ocular surface.1,3,5,6

Hydrophilic Shell

This protective hydrophilic shell allows for transport through the tear film onto the ocular surface.1,3,5

Image of NCELL with both the hydrophilic shell and hydrophobic core visible
Hydrophobic Core

This secured hydrophobic core prevents the encapsulated cyclosporine from being released until after penetrating the aqueous layer of the tear film.1,3,5,6

WHY NCELL MATTERS

Enhanced penetration of NCELL Technology2

Designed to protect cyclosporine during its delivery to the ocular surface.1,3,5

Blue and green eye icon next to the text Up to 3 times CsA concentration across the ocular tissues

NCELL provided superior delivery over emulsion

In a single-dose, preclinical study of cyclosporine delivered with NCELL Technology (0.05%) vs a commercially available cyclosporine emulsion (0.05%)1,2

Study design: Ocular tissue distribution of cyclosporine was evaluated in a total of 26 female New Zealand White rabbits that received a single dose (administered to both eyes) of vehicle, cyclosporine 0.05% or 0.1% with NCELL Technology, or a commercially available cyclosporine 0.05% emulsion (Restasis®, Allergan). Pharmacokinetic parameters for cyclosporine exposure were assessed in tears, whole blood, and ocular tissues.1,2

See the results patients experience while on CEQUA at 1, 2, and 3 months.

Visible Clinical Improvement
Indications and Usage

CEQUATM (cyclosporine ophthalmic solution) 0.09% is a calcineurin inhibitor immunosuppressant indicated to increase tear production in patients with keratoconjunctivitis sicca (dry eye).

Important Safety Information

Warnings and Precautions

Potential for Eye Injury and Contamination: To avoid the potential for eye injury and contamination, advise patients not to touch the vial tip to the eye or other surfaces.

Use with Contact Lenses: CEQUA should not be administered while wearing contact lenses. If contact lenses are worn, they should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following administration of CEQUA ophthalmic solution.

Adverse Reactions

The most common adverse reactions reported in greater than 5% of patients were pain on instillation of drops (22%) and conjunctival hyperemia (6%). Other adverse reactions reported in 1% to 5% of patients were blepharitis, eye irritation, headache, and urinary tract infection.

Please see the Full Prescribing Information.

Indications and Usage

CEQUATM (cyclosporine ophthalmic solution) 0.09% is a calcineurin inhibitor immunosuppressant indicated to increase tear production in patients with keratoconjunctivitis sicca (dry eye).

Important Safety Information

Warnings and Precautions

Potential for Eye Injury and Contamination: To avoid the potential for eye injury and contamination, advise patients not to touch the vial tip to the eye or other surfaces.

Use with Contact Lenses: CEQUA should not be administered while wearing contact lenses. If contact lenses are worn, they should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following administration of CEQUA ophthalmic solution.

Adverse Reactions

The most common adverse reactions reported in greater than 5% of patients were pain on instillation of drops (22%) and conjunctival hyperemia (6%). Other adverse reactions reported in 1% to 5% of patients were blepharitis, eye irritation, headache, and urinary tract infection.

Please see the Full Prescribing Information.

References: 1. US Patent 9,937,225 B2. 2. Data on file. Cranbury, NJ: Sun Pharmaceutical Industries, Inc. 3. Cholkar K, Gilger BC, Mitra AK. Topical, aqueous, clear cyclosporine formulation design for anterior and posterior ocular delivery. Transl Vis Sci Technol. 2015;4(3):1-16. 4. CEQUA [package insert]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2019. 5. Mandal A, Bisht R, Rupenthal ID, Mitra A. Polymeric micelles for ocular drug delivery: from structural frameworks to recent preclinical studies. J Control Release. 2017;248:96-116. 6. Cholkar K, Patel A, Vadlapudi AD, Mitra AK. Novel nanomicellar formulation approaches for anterior and posterior segment ocular drug delivery. Recent Pat Nanomed. 2012;2(2):82-95.