Highlights
Vuity (pilocarpine) is a new drug indicated for the treatment of presbyopia in adults.
Developed by AbbVie’s Allergan, Vuity is approved by the U.S. Food and Drug Administration (FDA).
A 30-day course of Vuity eye drops will cost a U.S. patient $86. The costs will have to be reimbursed out of pocket, as Vuity is unlikely to receive insurance coverage because it is “medically necessary”, as glasses are still a less expensive alternative.
Vuity will be in demand among people who are unhappy with having to put on and take off their reading glasses all day if, for example, their work requires them to constantly switch between near and far vision.
Vuity handles mild-to-moderate severity of presbyopia, the drug is less effective after age 65. Vuity should be used with caution when driving at night or performing hazardous activities in low light. There may also be some problems with changing focus between near and far vision. Contact lenses should be removed before using Vuity and then put back on after 10 minutes.
What is Presbyopia
Presbyopia (age-related farsightedness, senile hyperopia) is a physiological insufficiency of accommodation associated with the aging of the eye, which leads to a gradual deterioration of the ability to focus clearly on close objects.
Presbyopia, which is experienced by people over the age of 40, affects one in four people on Earth. The condition is similar to farsightedness (hypermetropia, hyperopia), which begins in childhood and manifests as symptoms of blurred vision at close distances.
Presbyopia, being a normal part of the aging process, results from age-related changes in the lens (decreased elasticity and increased hardness) and the strength of the ciliary muscle of the eye, causing the eye to focus light behind rather than on the retina when looking at close objects. Presbyopia is a type of refractive error (ametropia) along with myopia, hyperopia, and astigmatism.
Presbyopia can be corrected with glasses, contact lenses, multifocal intraocular lenses (artificial lens), and refractive surgery that changes the curvature of the cornea to better focus light on the retina: conductive keratoplasty, laser-assisted in situ keratomileusis (LASIK), laser-assisted sub-epithelial keratectomy (LASEK), photorefractive keratectomy (PRK), corneal inlays.
Vuity: Mechanism of Action of Pilocarpine in Presbyopia
Pilocarpine (AGN-190584), implemented in the formulation of eye drops, is a cholinergic muscarinic agonist that activates muscarinic receptors located at smooth muscles such as iris sphincter muscle (pupillary sphincter) and ciliary muscle. Contraction of the first causes the pupil to constrict, which improves near and intermediate visual acuity while maintaining some pupillary response to light. Contraction of the second shift the eye to a more myopic state.
Vuity’s know-how is represented by the optimized formulation of pilocarpine hydrochloride (1.25%) delivered by pHast technology, which allows the ophthalmic solution to rapidly adapt to the physiological pH of the tear film in order to improve patient comfort, enhance drug tolerance, and minimize blurred vision.
The effect of Vuity, which begins to take action as early as 15 minutes after dropping it in the eye, lasts up to 6 hours, improving near and intermediate vision without affecting far vision.
Vuity and Generic Pilocarpine: What Are the Differences?
Pilocarpine hydrochloride in the form of an ophthalmic solution has traditionally been used to treat glaucoma. [1] It is one of the oldest treatments for glaucoma, but because of its side effects pilocarpine is not always well tolerated and is currently not often prescribed for this therapeutic indication. [2] [3] [4]
Pilocarpine, being a cyclic ester, is highly susceptible to hydrolysis at physiological pH. A low pH (~4) is required to stabilize pilocarpine in ophthalmic solution. [5] However, at low pH pilocarpine is protonated or ionized, and therefore penetrates poorly through the cornea, [6] which limits its bioavailability. [7]
Existing pilocarpine-containing medications are known to cause brow pain, headache, eye discomfort, hyperemia, and blurred vision when instilled with drops. Examples of ocular surface discomfort that patients may experience include burning, pinching, and irritation. [3] [8] [9] [10] [11] [12] Studies have shown that pilocarpine caused more adverse events and more often led to discontinuation of therapy compared to other glaucoma treatment options. [9] [13] [14]. Patients also reported lower quality of life with pilocarpine and a higher preference for another glaucoma treatment option. [13] Low ophthalmic solution pH may be responsible for some of these side effects. [5]
Pilocarpine ophthalmic solution in the form of Vuity is designed to address pilocarpine tolerability issues in a way that quickly balances ocular surface pH, which in turn increases the unionized pilocarpine content, improving its bioavailability [7] and reducing side effects such as ocular discomfort and blurred vision.
A pilot clinical trial compared Vuity with generic pilocarpine among 5 patients with presbyopia. Participants were given Vuity in one eye and generic pilocarpine in the other. The mean blurred vision score was found to be statistically significantly lower with Vuity than with generic pilocarpine.
Adverse events such as eye pressure and/or pain, brow pain, blurred vision, burning, itching, and hypersensitivity to light were reported. All but one case of eye pressure and/or pain and one case of brow pain were reported with generic pilocarpine. According to the biomicroscopic examination, the mean rate of conjunctival hyperemia was lower with the administration of Vuity than with generic pilocarpine.
In vitro analysis showed that the pH of Vuity reached equilibrium with the physiological pH of the tear film (~6.5) faster, thereby not compromising its integrity. This explains better tolerance, less ophthalmic discomfort, and fewer adverse events.
Due to the immediate pH increase, which rapidly increases the non-ionized fraction of pilocarpine on the ocular surface, the ophthalmic bioavailability of Vuity is significantly higher than that of generic pilocarpine. This results in effective delivery of the drug to the anterior segment of the eye and contributes to its prolonged action.
Vuity: Efficacy and Safety of Pilocarpine in Presbyopia
Main Results
The efficacy and safety of Vuity were evaluated in the GEMINI 1 (NCT03804268) and GEMINI 2 (NCT03857542), two phase 3 (randomized, double-blind, placebo-controlled, multicenter) clinical trials, that enrolled adult (40–55 years) patients (n=750) with presbyopia.
Participants were given placebo or pilocarpine — one drop in each eye once a day for 30 days.
In both studies, the proportion of patients whose mesopic (dim light) high-contrast binocular distance-corrected near visual acuity (DCNVA) improved by 3 or more lines (according to the LogMAR chart) — with no loss of more than 1 line (5 letters) of corrected distance visual acuity (CDVA) with the same refractive correction — was statistically significantly greater in the pilocarpine group compared to the placebo group: 31% and 26% — versus 8% and 11% (p<0.01). The evaluation was performed on the 30th day of treatment, 3 hours after administration of the drug.
- It should be understood that a DCNVA improvement of at least 2 lines indicates a meaningful change in visual acuity for the patient, based on a number of psychometric assessment methods that comprehensively account for individual perception of such improvements.
Among the most common adverse reactions to pilocarpine prescribing, however, rare are headache, conjunctival hyperemia, blurred vision, eye pain, visual disturbances, eye irritation, and increased lacrimation.
Functional Near Vision
Administration of Vuity resulted in more patients than in the placebo group reaching functional near vision (DCNVA 20/40 or better). At the same time, the peak of treatment efficacy increased over the course of therapy, and tachyphylaxis (a rapid decrease in therapeutic effect with repeated use of the drug, i.e., the development of tolerance) was not observed.
Thus, on day 1 of treatment in the Vuity group, 73.9%, 82.4%, 87.5%, 77.7%, 71.0%, 72.1%, and 66.5% of patients achieved this status after 0.25, 0.5, 1, 3, 6, 8, and 10 hours pilocarpine postdosing, respectively. In the placebo group, the proportions were as follows: 58.6% (p<0.0001), 63.8% (p<0.0001), 68.0% (p<0.0001), 64.6% (p=0.0001), 63.3% (p=0.0264), 66.0%, and 64.8%.
On day 30 of treatment in the Vuity group, 80.9%, 86.6%, 92.7%, 87.6%, 79.6%, 78.2%, and 74.9% of patients reported functional near vision after 0.25, 0.5, 1, 3, 6, 8, and 10 hours pilocarpine postdosing, respectively. In the placebo group, the proportions were as follows: 74.5% (p=0.0415), 77.1% (p=0.0011), 78.9% (p<0.0001), 75.2% (p<0.0001), 76.3%, 74.0%, and 73.8%.
Presbyopia Severity
The therapeutic efficacy of Vuity correlated with the baseline severity of presbyopia. Thus, when treated with Vuity, patients with more severe presbyopia were more likely to start seeing more lines, while patients with less severe presbyopia were more likely to achieve functional near vision (DCNVA 20/40 or better).
For example, after 1 hour pilocarpine postdosing, when therapeutic efficacy peaked, the proportion of subjects in the subgroup with baseline presbyopia severity 20/40 or better who showed an improvement in DCNVA of 1 line or more was 75.0%, whereas for baseline severity 20/80 or worse, the proportion was 93.2%. Improvement of DCNVA by 3 or more lines was fair for 24.7% and 59.6% of patients in the 20/50 and 20/100 subgroups, respectively.
After 1 hour pilocarpine postdosing, 85.4%, 69.5%, and 46.6% in the 20/50, 20/63, and 20/80 subgroups of the initial presbyopia severity reached the status of functional near vision. After 3 hours, 75.3%, 46.3%, and 35.2%, and after 6 hours, 62.9%, 37.8%, and 20.5%.
Intermediate Vision
Vuity provided an improvement in intermediate vision based on a distance of 66 cm, the distance at which computer work typically occurs.
Thus, according to the distance-corrected intermediate visual acuity (DCIVA), which was evaluated at day 30 of treatment, administration of Vuity led to visual improvements of 7.7, 6.5, 4.8, 4.3, and 4.0 letters (5 letters — 1 line) after 1, 3, 6, 8, and 10 hours pilocarpine postdosing, respectively. In the placebo group, the results are as follows: 3.3 (p<0.0001), 3.0 (p<0.0001), 2.9 (p<0.0001), 2.8 (p=0.0001), and 2.4 letters (p<0.0001).
LASIK
Vuity managed to improve near visual acuity in patients with presbyopia who had previously undergone laser refractive surgery LASIK.
Thus, on the 30th day of treatment, DCNVA improved by 3 lines or more in 16.7%, 38.9%, 41.7%, 37.8%, 16.2%, 13.9%, and 8.3% of patients in the Vuity group — after 0.25, 0.5, 1, 3, 6, 8, and 10 hours pilocarpine postdosing, respectively. The proportions of participants in the placebo group are as follows: 0.0% (p=0.0087), 2.6% (p=0.0001), 10.5% (p=0.0022), 5.1% (p=0.0005), 7.7%, 2.6% and 0.0%.
The indicated improvement in near vision acuity was not statistically significantly different between the subgroups of patients treated with Vuity who had previously undergone LASIK and those who had not undergone this procedure: 16.8%, 32.7%, 39.0%, 28.0%, 17.4%, 12.6%, and 10.5%.
Patient Experience
A survey of participants (n=125) in the GEMINI clinical program found that 76% of those receiving Vuity stopped using reading glasses within the 10-hour therapy period; 84% expressed confidence that they would use Vuity when it became commercially available; and 83% reported that they intended to use Vuity at least 5 days a week.
Extras
Vuity (pilocarpine). Prescribing information. U.S. [PDF]