The CLARITY 1 (ClinicalTrials.gov Identifier: NCT05656027) and CLARITY 2 (ClinicalTrials.gov Identifier: NCT06045299) trials evaluated the efficacy and safety of LNZ100 (aceclidine 1.75% ophthalmic solution), a selective miotic, for the treatment of presbyopia in patients aged 45 to 75 years with a refractive range of -4.0D SE to +1.0D SE. The study included users who previously had LASIK surgery or an intraocular lens implant. 

The primary endpoint for both studies was the percentage of patients who achieved 3-lines or greater improvement in Best Corrected Distance Visual Acuity (BCDVA) at near without losing 1-line (5 letters or more of distance vision) at 3 hours post treatment.

Both trials met the primary and secondary near vision improvement endpoints (P <.0001).

In the brimonidine-controlled CLARITY 1 trial, 72% of participants treated with LNZ100 achieved 3 lines or greater improvement at 30 minutes. At 3 hours and 10 hours, 64% and 27%% of participants achieved 3-lines or greater improvement, respectively.

In the vehicle-controlled CLARITY 2 trial, 71% of LNZ100-treated patients achieved 3-lines or greater improvement at 30 minutes. At 3 hours and 10 hours, 71% and 40% of participants achieved 3-lines or greater improvement, respectively. Additionally, 95% of patients achieved 2-lines or greater improvement at 1 hour post treatment (P <.0001). 

Treatment with LNZ100 was also associated with a statistically significant improvement of 2–4 letters on distance vision in normal light and no negative impact to distance vision in low light at all time points (P <.0001). 

“We believe these data support LNZ100 as a potential best-in-class therapy for the treatment of presbyopia,” said Eef Schimmelpennink, President and Chief Executive Officer of LENZ Therapeutics. “The high responder rate, rapid onset and long duration across a broad range of presbyopes ranging from 45 to 75 years of age and having a refractive range from -4.0 to +1.0D SE are consistent with features that patients are expecting from an effective treatment option. Based on these highly encouraging data, we will direct our focus towards our NDA submission in mid-2024 for LNZ100, and preparations for commercialization in second half of 2025 upon FDA approval, with the goal of moving closer to helping many of the 128 million people experiencing symptoms of presbyopia in the United States.”

HealthDay News — There is an adverse association between calcium channel blocker (CCB) use and glaucoma, according to a study published online September 7 in JAMA Ophthalmology.

Alan Kastner, MD, from Moorfields Eye Hospital National Health Service Foundation Trust and University College London, and colleagues examined the association between systemic CCB use and glaucoma and related traits in a population-based cross-sectional study involving UK Biobank participants with complete data for analysis of glaucoma status, intraocular pressure (IOP), and optical coherence tomography-derived inner retinal layer thicknesses. Data were included for 427,480 adults (median age, 58 years), including 33,175 CCB users (7.8%).

The researchers found that use of CCBs, but not other antihypertensive agents, was associated with increased odds of glaucoma after adjustment for key sociodemographic, medical, anthropometric, and lifestyle factors (odds ratio, 1.39). CCB use was also associated with thinner macular ganglion cell-inner plexiform layer and macular retinal nerve fiber layer thickness (−0.34 and −0.16 µm, respectively), but not with IOP.

“This cross-sectional study adds further support to an adverse association between CCB use and glaucoma, despite no apparent association with IOP,” the authors write. “This warrants further investigation to determine whether the associations are causal and to probe potential underlying biological mechanisms.”

Several authors disclosed ties to the pharmaceutical industry.

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The Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for aflibercept 8mg for the treatment of patients with wet age-related macular degeneration (wAMD), diabetic macular edema (DME), and diabetic retinopathy.

The BLA is supported by data from the phase 3 PULSAR (N=1009; ClinicalTrials.gov Identifier: NCT04423718) and phase 2/3 PHOTON (N=658; ClinicalTrials.gov Identifier: NCT04429503) trials, which compared the efficacy and safety of aflibercept 8mg to Eylea (aflibercept 2mg) in patients with wAME and DME, respectively. Patients were randomly assigned to receive aflibercept 8mg every 12 weeks or every 16 weeks or aflibercept 2mg every 8 weeks. The primary endpoint for both trials was the change from baseline to week 48 in best corrected visual acuity. 

Results from both trials showed that treatment with aflibercept 8mg met the primary endpoint demonstrating noninferior vision gains at week 48 with both the 12- and 16-week dosing regimens after initial monthly doses vs aflibercept 2mg every 8 weeks. The majority of patients treated with aflibercept 8mg were able to maintain the 12- and 16-week dosing regimens through week 48.

In PULSAR, 71% and 67% of wAMD patients treated with aflibercept 8mg 12- and 16-week dosing regimens, respectively, had no retinal fluid in the center subfield compared with 59% of patients who received aflibercept 2mg. The median time to fluid-free subfield was 4 weeks for aflibercept 8mg vs 8 weeks for aflibercept 2mg.

In PHOTON, DME patients treated with aflibercept 8mg 12- and 16-week dosing regimens had a mean reduction in the total area of fluorescein leakage from baseline of 14mm² and 9mm², respectively, vs 9mm² for aflibercept 2mg.

Aflibercept 8mg was found to have a similar safety profile to aflibercept 2mg. No cases of retinal vasculitis, occlusive retinitis or endophthalmitis were observed in either trial.

The FDA has assigned a target action date of June 27, 2023 for the application.

References

1. Aflibercept 8mg BLA for treatment of wet age-related macular degeneration and diabetic macular edema accepted for FDA Priority Review. News release. Regeneron Pharmaceuticals, Inc. Accessed February 23, 2023. https://www.globenewswire.com/news-release/2023/02/23/2614121/0/en/Aflibercept-8-mg-BLA-for-Treatment-of-Wet-Age-Related-Macular-Degeneration-and-Diabetic-Macular-Edema-Accepted-for-FDA-Priority-Review.html.
2. Aflibercept 8mg late-breaking data presented at Retina Society in diabetic macular edema and wet age-related macular degeneration. News release. Regeneron Pharmaceuticals, Inc. November 4, 2022. Accessed February 23, 2023. https://investor.regeneron.com/news-releases/news-release-details/aflibercept-8-mg-late-breaking-data-presented-retina-society.

HealthDay News — Large language models (LLMs) like ChatGPT can respond to patient-written ophthalmology questions and usually generate appropriate responses, according to a study published online August 22 in JAMA Network Open.

Isaac A. Bernstein, from Stanford University in California, and colleagues examined the quality of ophthalmology advice generated by an LLM chatbot compared with ophthalmologist-written advice. The study used deidentified data from an online medical forum, in which patient questions received responses written by ophthalmologists. A masked panel of 8 board-certified ophthalmologists were asked to differentiate between answers generated by the ChatGPT chatbot and answers from ophthalmologists.

Two hundred pairs of user questions and answers were assessed. The researchers found that the mean accuracy was 61.3% for differentiating artificial intelligence (AI) and human responses. Of 800 assessments of chatbot-written answers, 21.0 and 64.6% were marked as human-written and AI-written, respectively. Chatbot answers were more often rated as probably or definitely written by AI compared with human answers. The likelihood of chatbot answers containing incorrect or inappropriate material and likelihood of harm was comparable with human answers.

“We intend for this study to catalyze more extensive and nuanced dialogue and joint efforts surrounding the use of LLMs in ophthalmology among various health care stakeholders, including patients, clinicians, researchers, and policy makers,” the authors write. “The primary goal is to prudently leverage these early research findings to shape the responsible implementation of LLMs in the field of ophthalmology.”

Abstract/Full Text

Andy S. Huang, MD, from the Icahn School of Medicine at Mount Sinai in New York City, and colleagues conducted a comparative cross-sectional study recruiting 15 participants aged 31 to 67 years, including 12 attending physicians and 3 senior trainees, to compare the diagnostic accuracy and comprehensiveness of responses from an LLM chatbot with those of fellowship-trained glaucoma and retina specialists. Responses were assessed via a Likert scale for glaucoma and retina questions (10 of each type) in deidentified glaucoma and retina cases (10 of each type).

The researchers found that the combined question-case mean rank for accuracy was 506.2 and 403.4 for the LLM chatbot and glaucoma specialists, respectively; the corresponding mean ranks for completeness were 528.3 and 398.7. The mean rank for accuracy was 235.3 and 216.1 for the LLM chatbot and retina specialists, respectively; the corresponding mean ranks for completeness were 258.3 and 208.7. A significant difference was seen between all pairwise comparisons, except for specialist vs trainee, in rating chatbot completeness in the Dunn test. Compared with their specialist counterparts, both trainees and specialists rated the chatbot’s accuracy and completeness more favorably, with specialists noting a significant difference in the accuracy and completeness of the chatbot.

“These findings support the possibility that artificial intelligence tools could play a pivotal role as both diagnostic and therapeutic adjuncts,” the authors write.

Abstract/Full Text

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Akorn has initiated a voluntary recall of various within-expiry drug products as the company has shut down operations and is unable to assure the quality of the products.

The recalled products were distributed nationwide to wholesalers, retailers, manufacturers, medical facilities, and repackagers and via the Internet to consumers. The discontinuation of the Company’s Quality program means that it is unable to support or guarantee that the medications will meet all intended specifications through the labeled shelf life of the product.

All NDCs and Lots of the following Akorn products have been recalled:

• Acetaminophen & Codeine Phosphate Oral Solution 120mg & 12mg/5mL
• Acetic Acid Otic Solution
• Acyclovir Oral Suspension, 200mg/5mL
• Albuterol Sulfate Syrup, 2mg (base)
• Amantadine HCl Syrup, USP 50mg per 5mL
• Apraclonidine Ophthalmic Solution 0.5%
• Artificial Tears
• Atropine Sulfate Ophthalmic Solution
• Azelastine Hydrochloride Nasal Spray, 0.1%
• Bacitracin Zinc and Polymyxin B Sulfate Ophthalmic Ointment, 3.5g
• Calcipotriene Scalp Solution, 0.005%
• Calcitriol Injection 1mcg and 2mcg
• Cetrorelix Acetate for Injection, 0.25mg/vial, Single-Dose Vial
• Ciclopirox Topical Solution 8%
• Cimetidine HCl Oral Solution
• Clobetasol Propionate Cream 0.05%
• Clobetasol Propionate Ointment, 0.05%
• Clobetasol Propionate Shampoo, 0.05%
• Cromolyn Sodium Ophthalmic Solution 4%
• Detomidine Hydrochloride 20mL and 5mL
• Dicyclomine Hydrochloride Injection USP, 20mg/2 mL (10mg/mL)
• Diuril^® (chlorothiazide sodium) Injection
• DOCU LIQUID- docusate sodium liquid
• Ephedrine Injection 50mg/mL
• Fentanyl Citrate Injection
• Ferrous Sulfate Elixir and Iron Supplement
• Fluticasone Propionate Nasal Spray
• Gonak Hypromellose Ophth Sol
• Granisetron HCl Injection 1mg/mL
• Guaifenesin and Codeine Phosphate Liquid
• Hydralazine HCl Injection
• Hydrocortisone and Acetic Acid Otic Solution
• Hydromorphone High Potency Injection USP – Ampule and Vial
• IC-Green Sterile Indocyanine Green Injection USP
• Ketorolac Tromethamine Ophthalmic Solution, 0.5%
• Lactulose Syrup (Oral) and (Oral/Rectal)
• Levetiracetam Injection USP, 500mg/5 mL (100mg/mL) single-dose vial
• Levocarnitine Oral Solution, USP
• Levofloxacin Injection, 25mg/mL
• Levofloxacin Oral Solution
• Levofloxacin Opth Solution
• Lidocaine 2.5% & Prilocaine 2.5% Cream
• Lidocaine Ointment
• Lidocaine HCl Jelly USP, 2%
• Lidocaine Hydrochloride Oral Topical Solution, USP (Viscous) 2%
• Lorazepam Injection 2mg/mL vial
• Lorazepam Oral Concentrate, 2mg
• Megestrol Acetate Oral Suspension 40mg/mL
• Midazolam Injection USP 1mg/mL & 5mg/mL – vial
• Moxifloxacin HCl Solution 0.5%  
• Naloxone Injection 0.4mg/mL; 1mL and 10mL Vial
• Neomycin & Polymyxin B Sulfates & Bacitracin Zinc Ophthalmic Ointment
• Olopatadine HCl Nasal Spray, 665mcg/spray
• Olopatadine Solution 0.1% and 0.2%   
• Oxcarbazepine Oral Suspension USP, 300mg/5 mL
• Pilocarpine 1, 2, & 4%         
• Prednisolone Sodium Phosphate Oral Solution
• Promethazine HCl & Codeine Phosphate Oral Solution
• Promethazine HCl Oral Solution
• Proparacaine HCl Ophthalmic Solution, 0.5%
• Rifampin Capsules USP, 150mg & 300mg
• Ropivacaine Hydrochloride Injection USP, 0.2% and 5mg/mL
• Sodium Chloride Ophthalmic Ointment
• Sodium Chloride Solution Drops
• Sodium DIURIL
• Sufenta (Sufentanil Citrate Injection, USP) 50 mcg/mL
• Sulfamethoxazole & Trimethoprim Oral Suspension USP, 200mg/40mg per 5mL
• Timolol Maleate Ophthalmic Solution 0.5%, 2.5, 5, 10, & 15mL
• Tobramycin Inhalation Solution USP, 300mg/5 mL
• Tobramycin Ophthalmic Solution 0.3%
• Trihexyphenidyl HCl Oral Sol
• Tropicamide Ophthalmic Solution 0.5% and 1%
• Valproic Acid Oral Solution
• Vitamin D Suppl. Drops 50mL
• Xopenex– levalbuterol hydrochloride solution, concentrate

Further distribution or use of these recalled products should be discontinued immediately. To date, the Company has not received any reports of adverse events related to this recall.

Adverse events or quality issues should be reported to the FDA’s MedWatch Adverse Event Reporting program. Consumers with questions regarding this recall can contact Akorn at (800) 932-5676.

Fluorometholone ophthalmic suspension is indicated for the treatment of corticosteroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe. The treatment is administered as 1 drop into the conjunctival sac 2 to 4 times daily. During the first 24 to 48 hours, the dosing frequency may be increased to 1 application every 4 hours. 

Patients should be reevaluated if signs/symptoms fail to improve after 2 days. Intraocular pressure should be monitored if the product is used for 10 days or longer.

Amneal’s Fluorometholone Ophthalmic Suspension 0.1% is supplied as a sterile, white to off-white homogenous suspension in 10mL bottles containing 5mL of product and in 15mL bottles containing 10mL of product.

Apellis announced that as part of its investigation into real-world safety events with Syfovre^® (pegcetacoplan), it was reported that the 19-gauge filter needle supplied in certain injection kits has internal structural variations.

Syfovre is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The product is administered by intravitreal injection to the affected eye. The filter needle is used to withdraw the drug from the vial for this procedure.

While a causal relationship between the 19-gauge filter needle and the rare adverse event of retinal vasculitis has not been established, Apellis Pharmaceuticals is recommending that health care providers discontinue use of the injection kits that contain the 19-gauge filter need and use the injection kits with the 18-gauge filter needle. These updated kits have already been distributed.

“Based on the findings from our investigation, we believe it is prudent that practitioners only use the kits with the 18-gauge filter needle, which are already in distribution,” said Caroline Baumal, MD, chief medical officer of Apellis. “This recommendation is out of an abundance of caution as patient safety is our top priority.”

In a statement, the Company reported that a total of 8 events of retinal vasculitis have been confirmed; all were observed after the first Syfovre injection. “To date, more than 100,000 vials have been distributed for commercial use and for administration in clinical trials, and the events of retinal vasculitis continue to be very rare at an estimated real-world rate of 0.01% per injection,” added Baumal.

The approval of Syfovre was based on data from the phase 3 DERBY (ClinicalTrials.gov Identifier: NCT03525600) and OAKS (ClinicalTrials.gov Identifier: NCT03525613) studies, which evaluated the efficacy and safety of intravitreal Syfovre vs sham in 1258 patients with GA secondary to AMD for 24 months. In both trials, Syfovre reduced the rate of GA lesion growth and demonstrated increasing treatment effects over time. The most common adverse reactions reported in clinical trials were ocular discomfort, neovascular AMD, vitreous floaters, and conjunctival hemorrhage.

The table below is a review of notable updates that occurred in April 2023 for investigational products in development (not an inclusive list). Click on the status to view our full coverage.