Global Pharma Healthcare is voluntarily recalling all lots within expiry of Artificial Tears Lubricant Eye Drops to the consumer level due to possible contamination.

The recalled lots of Artificial Tears Lubricant Eye Drops, 10mg in 1mL, ½ fl oz (15mL) bottles were distributed nationwide by EzriCare, LLC (NDC 79503-0101-15; UPC 79503 10115 7) and Delsam Pharma (NDC 72570-121-15; UPC 72570-0121-15). Artificial Tears Lubricant Eye Drops are used as a protectant against further irritation or to relieve dryness of the eye for the temporary relief of discomfort due to minor irritations of the eye, or to exposure to wind or sun. 

A recent communication from the Centers for Disease Control and Prevention (CDC) alerted to a multistate cluster of Verona Integron-mediated Metallo-β-lactamase (VIM)- and Guiana-Extended Spectrum-β-Lactamase (GES)- producing carbapenem-resistant Pseudomonas aeruginosa (VIM-GES-CRPA) infections possibly associated with the use of the artificial tears manufactured by Global Pharma Healthcare.

The Company has stated that the use of contaminated artificial tears may result in the risk of eye infections leading to permanent vision loss. To date, there have been 55 reports of adverse events resulting in ocular infections, permanent loss of vision, and 1 death from bloodstream infection.

Adverse reactions or quality problems should be reported to the Food and Drug Administration’s MedWatch program.

Reference

Global Pharma Healthcare issues voluntary nationwide recall of Artificial Tears Lubricant Eye Drops due to possible contamination. News release. Global Pharma Healthcare. February 2, 2023. Accessed February 3, 2023. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/global-pharma-healthcare-issues-voluntary-nationwide-recall-artificial-tears-lubricant-eye-drops-due

The Centers for Disease Control and Prevention (CDC) is urging health care providers and patients to immediately discontinue use of EzriCare Artificial Tears as the Agency is currently investigating its link to multiple different infection types, including eye infections.

From May 17, 2022 to January 19, 2023, the CDC, alongside state and local health departments, has identified 56 isolates from 50 case patients across 11 states with Verona Integron‐mediated Metallo‐β‐lactamase (VIM)‐ and Guiana‐Extended Spectrum‐β‐Lactamase (GES)‐ producing carbapenem‐resistant Pseudomonas aeruginosa (VIM‐GES‐CRPA). These isolates were identified from clinical cultures of the cornea (10), sputum or bronchial wash (11), urine (6), other nonsterile sources (4), blood (2), and rectal swabs (23) collected for surveillance.

Among these cases, permanent vision loss resulting from ocular infection, hospitalization, and death (1 patient with bloodstream infection) have been reported. In addition to being resistant to carbapenems, the isolates in this cluster have been found to be resistant to ceftazidime and cefepime.

A review of common exposure showed that a majority of these individuals used artificial tears prior to identifying the VIM-GES-CRPA infection. The most common brand reported was EzriCare Artificial Tears, a preservative-free product dispensed in multidose bottles. Testing of opened EzriCare bottles revealed the presence of VIM‐CRPA. The CDC is continuing to test to see if the outbreak strain is present in unopened bottles.

According to a statement from EzriCare, the Company has not received consumer complaints or adverse event reports related to this investigation to date. Moreover, it has not been asked to conduct a recall or received communication from any regulatory agency providing any outcomes or details regarding the ongoing investigation.

Reference

Update: multistate cluster of VIM- and GES-producing carbapenem-resistant Pseudomonas aeruginosa associated with Artificial Tears. News release. Centers for Disease Control and Prevention. Accessed February 1, 2023. https://www.aao.org/Assets/3a187c94-7889-42e8-84a1-6b2e88e7d374/638098403609770000/epix-multistate-pseudomonas-investigation-20jan2023-pdf?inline=1.

Dry Eye Treatments

Capivasertib for Hormone Receptor (HR)-Positive Advanced Breast Cancer

PDUFA date: 12/2023

Capivasertib is an oral selective adenosine triphosphate (ATP)-competitive inhibitor of all 3 AKT isoforms. It is under Priority Review for use in combination with fulvestrant, in the treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, following recurrence or progression on or after an endocrine-based regimen. The NDA is supported by data from the phase 3 CAPItello-291 trial (ClinicalTrials.gov Identifier: NCT04305496). In the overall study population, capivasertib plus fulvestrant reduced the risk of disease progression or death by 40% compared with placebo plus fulvestrant.

Exagamglogene autoemcel (Exa-cel) for Sickle Cell Disease

PDUFA date: 12/8/2023

Exa-cel is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients with severe sickle cell disease. The BLA submission includes results from the phase 3 CLIMB-121 study (ClinicalTrials.gov Identifier: NCT03745287), which included 35 patients with sickle cell disease who received a single dose of exa-cel; 17 patients were evaluable at the time of data cutoff. Findings from a pre-specified interim analysis showed that 94.1% (16/17) of patients achieved the primary endpoint of freedom from vaso-occlusive crises for at least 12 consecutive months.

Roflumilast Foam 0.3% for the Treatment of Seborrheic Dermatitis

PDUFA date: 12/16/2023

Roflumilast foam is a topical formulation of a highly potent and selective phosphodiesterase type 4 inhibitor. The NDA is supported by data from the phase 3 STRATUM trial (ClinicalTrials.gov Identifier: NCT04973228), which included 457 patients 9 years of age and older with moderate to severe seborrheic dermatitis. The study met its primary endpoint (Investigator Global Assessment [IGA] Success at week 8), with 79.5% of roflumilast-treated patients achieving IGA success vs 58% of those who received vehicle (P <.0001).

Lovotibeglogene autoemcel (Lovo-cel) for Sickle Cell Disease

PDUFA date: 12/20/2023

Lovo-cel is an investigational one-time gene therapy designed to add functional copies of a modified form of the β-globin gene into a patient’s own hematopoietic stem cells. This allows for the production of anti-sickling adult hemoglobin. The treatment is under Priority Review for patients with sickle cell disease who have a history of vaso-occlusive events. The BLA submission includes efficacy data for 36 patients from the HGB-206 study (ClinicalTrials.gov Identifier: NCT02140554) and 2 patients from the HGB-210 study (ClinicalTrials.gov Identifier: NCT04293185).

Dasiglucagon for Hypoglycemia in Congenital Hyperinsulinism

PDUFA date: 12/30/2023

Dasiglucagon is a glucagon analog formulated in a ready-to-use aqueous solution. It is being reviewed for congenital hyperinsulinism (CHI), a rare genetic disease that affects newborns and children resulting in persistent hypoglycemia due to the overproduction of insulin.The NDA is supported by data from two phase 3 trials (ClinicalTrials.gov Identifier: NCT04172441; NCT03777176) and an ongoing long-term extension trial (ClinicalTrials.gov Identifier: NCT03941236). The FDA is conducting its review in 2 parts under the same NDA. A decision on part 1, which relates to the use of dasiglucagon for the prevention and treatment of hypoglycemia in pediatric patients 7 days of age and older with CHI for up to 3 weeks of dosing, is expected in December. Part 2 relates to the use of the product beyond 3 weeks.

Reproxalap is a first-in-class small-molecule modulator of reactive aldehyde species (RASP). It works by covalently binding to free aldehydes, thereby diminishing excessive RASP levels, which are generally elevated in ocular and systemic inflammatory disease.

The NDA included efficacy and safety data from 5 clinical trials, including the phase 3 TRANQUILITY-2 study (ClinicalTrials.gov Identifier: NCT05062330), which included 361 patients with dry eye disease.

According to the letter, the application for reproxalap could not be approved in its current form because it “did not demonstrate efficacy in treating ocular symptoms associated with dry eyes.” The FDA requested an additional trial be conducted “to demonstrate a positive effect on the treatment of ocular symptoms of dry eye.” 

In November, Aldeyra submitted a Special Protocol Assessment (SPA) to the FDA for a dry eye disease chamber crossover clinical trial. The Agency has 45 days to review the SPA and provide feedback. An SPA agreement indicates that the FDA finds the overall trial protocol to be adequate and acceptable for a study intended to support a marketing application. Pending SPA feedback, the Company expects top-line results from the proposed trial in the first half of 2024.

“If the SPA and proposed trial results are successful, and the potential resubmitted NDA is approved, the drug label may be the first label in dry eye disease to contain acute reduction in ocular redness, as well as a combination of chronic and acute symptomatic benefit, potentially highlighting the rapid activity of reproxalap on both signs and symptoms of dry eye disease,” stated Todd C. Brady, MD, PhD, President and CEO of Aldeyra Therapeutics.

Reproxalap is also being evaluated for the treatment of allergic conjunctivitis. The Company announced topline data in June 2023 from its phase 3 INVIGORATE-2 trial.

Amniotic fluid eyedrops have not been approved to treat diseases or conditions such as dry eye by the Food and Drug Administration (FDA), according to a recent communication from the agency.

The alert was issued to inform the public that certain manufacturers have been marketing and distributing amniotic fluid eyedrops for use in the treatment of ophthalmic diseases and conditions that have not been reviewed or approved by the FDA. In late 2022, the agency sent letters to the manufacturers of Regener-Eyes^® Ophthalmic Solution and StimulEyes to inform them that their products do not comply with the Public Health Service Act, the Federal Food, Drug, and Cosmetic Act, and other applicable regulations.

At this time, amniotic eyedrop products may only be offered to patients if an investigational new drug application (IND) is in effect. It is recommended that patients inquire about the status of the IND prior to consenting to treatment.

Patients and health care providers are encouraged to report any adverse events related to the use of amniotic fluid eyedrops to the FDA’s MedWatch program.

The Food and Drug Administration (FDA) has approved Miebo (perfluorohexyloctane ophthalmic solution) for the treatment of the signs and symptoms of dry eye disease.

While its exact mechanism of action in the treatment of dry eye disease is unknown, Miebo, a semifluorinated alkane, forms a monolayer at the air-liquid interface of the tear film that can be expected to reduce evaporation.

The approval was based on data from the phase 3 GOBI (ClinicalTrials.gov Identifier: NCT04139798) and MOJAVE (ClinicalTrials.gov Identifier: NCT04567329) studies, which evaluated the efficacy and safety of Miebo in a total of 1217 adults 18 years of age and older with dry eye disease and clinical signs of meibomian gland dysfunction. Patients were randomly assigned 1:1 to receive either Miebo or hypotonic saline solution 4 times daily.

The coprimary endpoints for both studies were the change from baseline to day 57 in total corneal fluorescein staining (tCFS), as assessed by the National Eye Institute scale, and in Dryness Score, as assessed on a visual analogue scale (VAS).

Findings demonstrated a statistically significant improvement in tCFS at day 57 in the Miebo arm compared with the saline arm in both the GOBI (-2.0 [2.6] vs -1.0 [2.7], respectively; P <.001) and MOJAVE (-2.3 [2.8] vs -1.1 [2.9], respectively; P <.001) studies. 

Additionally, Miebo was associated with a statistically significant improvement in VAS eye dryness score on day 57 vs saline in both the GOBI (-27.4 [27.9] vs -19.7 [26.7], respectively; P <.001) and MOJAVE (-29.5 [28.6] vs -19.0 [27.2], respectively; P <.001) studies. Statistically significant improvements in tCFS and VAS eye dryness score were also observed at day 15 (secondary endpoint). The most common adverse event reported was blurred vision.

“Today’s FDA approval of Miebo further advances DED treatment by addressing a significant unmet need for millions of people suffering with this disease,” said Brent Saunders, chairman and CEO, Bausch + Lomb. “We are proud to bring to market the first and only prescription eye drop approved in the United States for the treatment of DED that directly targets evaporation. We expect to make Miebo commercially available in the second half of this year.”

Miebo (perfluorohexyloctane ophthalmic solution) is now available for the treatment of the signs and symptoms of dry eye disease.

The prescription eye drop contains perfluorohexyloctane, a semifluorinated alkane that directly targets tear evaporation by forming a monolayer at the air-liquid interface of the tear film. The safety and efficacy of Miebo was established in the phase 3 GOBI (ClinicalTrials.gov Identifier: NCT04139798) and MOJAVE trials (ClinicalTrials.gov Identifier: NCT04567329), which enrolled patients with dry eye disease and clinical signs of meibomian gland dysfunction.

Miebo is supplied in a multiple-dose 5mL bottle; it can be stored at room temperature and used until the expiration date on the bottle. The recommended dosage of Miebo is 1 drop 4 times daily into the affected eye(s). Patients who wear contact lenses should remove them prior to and for at least 30 minutes after administering Miebo. 

“More and more Americans are suffering from dry eye disease, due in large part to today’s multi-screen lifestyles,” said Andrew Stewart, president, Global Pharmaceuticals and International Consumer, Bausch + Lomb. “With Miebo, eye care professionals now have a prescription eye drop that directly addresses tear evaporation, the leading cause of dry eye disease.”

The safety and effectiveness of Miebo have not been established in patients younger than 18 years of age.

The FDA and CDC greenlight updated COVID-19; prescription drug for dry eye disease now available; head-to-head study compares Skyrizi to Stelara for Crohn disease; the REMS program has been updated for IBS treatment Lotronex; and the FDA cracks down on companies selling unapproved eye products.