David Hutton

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 cases continue to spike in many parts of the United States, health officials continue to deal with myriad shortages, including much-needed medications.

Treatment delays, even temporary, can be detrimental to a patient’s health. The U.S. Food and Drug Administration (FDA) can take action to help prevent drug shortages and protect treatment access without compromising the 

Over the last several months, Prevent Blindness, has stepped up to ensure that patients do not face shortages of medications that help protect their vision. The organization is concerned about shortages of teprotumumab (Tepezza, Horizon Therapeutics).

Jeff Todd, president and CEO of Prevent Blindness, pointed out that the Food and Drug Administration in 2020 approved teprotumumab for the treatment of thyroid eye disease (TED). 

He has lead the organization’s efforts to guard against potential lapses in therapy for patients living with TED. Teprotumumab currently is the only FDA-approved treatment of the underlying causes of TED.

Sara Brown, director of government affairs at Prevent Blindness, noted that the organization is concerned that the manufacturing of teprotumumab has been limited due to the manufacture of the COVID-19 vaccine.

“We believe the production of the COVID-19 vaccine is of the utmost importance,” she said. “As we understand it, there are some mechanisms that the FDA could take to ensure the manufacture of teprotumumab without disruption of production of the vaccine.”

Brown noted that there are patients across the country who are in the midst of treatment with the drug, and without that continued treatment their vision could be adversely impacted.

Teprotumumab received FDA approval in 2020 and that could play a factor in how much is available. As the only drug of its kind in the market, the stock is not plentiful.

“We have concerns considering that the FDA in the past has used its authority to prevent drug shortages,” Brown said. “We would hope that they use this precedence”

When the Coronavirus Aid, Relief, and Economic Security (CARES) Act was signed into law on March 25, 2020, lawmakers included a provision amending the drug shortage reporting requirements and creating new requirements related to medical device shortages.

Congress anticipated potential shortfalls with other medications and built language into the CARES Act to guard against these issues. It granted the FDA the ability to thwart shortages.

“Congress directed the FDA to be able to expedite and prioritize applications or inspections that could mitigate or prevent a drug shortage,” Todd said. “The FDA can prioritize to review relevant data and can institute strategies to release individual batches of drugs.”

Over the last 10 months, there has been an increased demand for products used to diagnose and treat COVID-19 patients. This has placed stress on the manufacturing and delivery of vital products, having more information about drug, drug ingredient, and device shortages has been seen as more critical.

The CARES Act expands the scope of drug products subject to notification. Previously, drug manufacturers were required to notify the Food and Drug Administration (FDA) of shortages or expected shortages of drugs that are “life-supporting, life-sustaining, or intended for use in the prevention or treatment of a debilitating disease or condition.”

The FDA notes that it has been closely monitoring the medical supply chain “with the expectation that it may be impacted by the COVID-19 outbreak, potentially leading to supply disruptions or shortages of drug and biologic products in the US,” and adds that notifying the FDA according to this guidance will help the agency to prevent or mitigate shortages.

The FDA added that it maintains public lists of drugs and biologics that are subject to shortages. The list includes the name of the product, the reason for the shortage, and the estimated shortage duration, based on information submitted by the manufacturer. This posted information may also include information that the manufacturer makes available to stakeholders and patients about the shortage.

“It is critical that the treatment is not delayed and is provided without interruption during the active phase,” Todd said. “As an organization dedicated to protecting patients from avoidable vision loss, ensuring patients have access to therapies that can address the devastating and sight-threatening consequences of TED is a significant priority.”

While the group has not heard any anecdotal information from ophthalmologists regarding shortages of teprotumumab, it noted that ophthalmologists are aware of the potential for shortfalls in the supply.

“We have heard from patients who have expressed a concern about the shortage, and are already facing treatment disruption,” Todd said.

Unlike other ophthalmic medications, teprotumumab is in a unique position as a newly approved drug and as a first-of-its-kind treatment option for TED.

“One of the challenges is that some of the other drugs have been out longer and have larger supplies produced,” Todd said. “Teprotumumab, because it is new, does not have the backup supply.”

Going forward, Brown said the organization will take its case to Congress, if necessary.

“We will continue to encourage the FDA to use the authority it has received from Congress to head off any potential shortages,” she concluded.

Articles

Amid ramped up production of vaccines, CARES Act gives FDA power to head off potential drug shortfalls. Prevent Blindness is urging the FDA to use its authority to ensure TED treatment drug supply isn’t interrupted. 


As COVID-19 focuses attention on vaccine, medication shortages loom

Surface Ophthalmics Inc. has announced positive top-line results from the Phase II trial for betamethasone 0.2% (SURF-201), an investigational therapy for the treatment of post-cataract surgery pain and inflammation.

With twice-daily dosing, betamethasone 0.2% met its primary endpoints of absence of inflammation at both Day 8 and Day 15, according to the report. 

Betamethasone 0.2% is a potent corticosteroid, formulated as a solution in Surface’s patented Klarity vehicle, and is intended to provide improved efficacy and safety when compared to currently used corticosteroids. The drug marks the first ophthalmic therapeutic in the United States to utilize betamethasone, as well as being the first preservative-free unit dose therapy for the treatment of post–operative pain and inflammation.

The trial involved 91 patients and met the primary endpoints of complete clearance of anterior chamber cells, which is a marker for inflammation, at both Day 8 and Day 15 with p-values of 0.01 and 0.001, respectively. While betamethasone 0.2% was dosed at only twice per day, a higher percentage of patients were inflammation free by the end of the dosing when compared to the previously reported results of all other branded corticosteroids.

In addition to inflammation, when looking at the secondary endpoint, an unprecedented high percentage of almost 90% of patients were pain free at Day 15. Overall, betamethasone 0.2% was found to be safe and well-tolerated and there was zero incidence of intraocular pressure increase of more than 10 mm Hg from the base and exceeding the 22 mm Hg mark.

“The extremely positive data affirms not only the potential for this product, but also the merit of the common building blocks found across the therapies in our pipeline,” Kamran Hosseini, MD, PhD, president and CEO of Surface Ophthalmics, said in a statement.

According to Hosseini, based on the date, the drugmaker is confident that its building block approach to product development will continue to demonstrate positive results and allow it to fully recognize the potential of its pipeline to offer innovative solutions for unmet patient needs in the ophthalmic space.

Surface Ophthalmics is advancing three clinical programs: one in chronic dry eye disease (SURF-100), one in episodic dry eye disease (SURF-200), and one in pain and inflammation following ocular surgery (SURF-201). These programs utilize Klarity as the delivery vehicle, which has a proven track record of protecting and rehabilitating the ocular surface.

The investigational therapy met all primary endpoints of absence of inflammation at both Day 8 and Day 15 for the treatment of pain and inflammation following cataract surgery. 

Betamethasone 0.2% gets positive marks in Phase II trial for treatment of post-cataract surgery pain, inflammation

Bausch + Lomb is kicking off the first of two Phase 3 studies evaluating perfluorohexyloctane (NOV03, Novaliq) as a first-in-class investigational drug with a novel mechanism of action to treat the signs and symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD) with the enrollment of 599 participants.

Additionally, in the SEECASE Phase 2 clinical study, perfluorohexyloctane met its primary efficacy endpoint of statistically significant improvement of total corneal fluorescein staining over control at eight weeks. 

Perfluorohexyloctane also showed statistically significant improvement of certain symptoms, such as severity and frequency of dryness and burning/stinging of the eyes, over the entire duration of the Phase 2 study.

“We are committed to addressing the unmet needs of patients, and believe NOV03, if approved, may be a first-in-class treatment option for the millions of patients who suffer from Dry eye disease associated with Meibomian gland dysfunction,” Joseph C. Papa, chairman and CEO, Bausch Health, said in a statement. “This continued progress in our Phase 3 program and the published results of the SEECASE study are both exciting milestones in our development journey for perfluorohexyloctane.”

SEECASE was a prospective, multicenter, randomly assigned, double-masked, saline-controlled clinical study that evaluated perfluorohexyloctane at two dosing regimens.

The data published was based on results from 336 patients age 18 years or older who were randomized to one of four treatment groups: perfluorohexyloctane four times daily (QID), perfluorohexyloctane twice daily (BID), saline BID or saline QID (a 2:2:1:1 ratio).

The study met its primary efficacy endpoint of statistically significant improvement of total corneal fluorescein staining (tCFS) over control at eight weeks. Data showed a change from baseline of tCFS over control, for both dosing regimens (QID and BID, P < 0.001 and P = 0.009, respectively). 

Effects on tCFS and symptoms started at two weeks after start of treatment and were maintained over the study duration. The effects were dosing schedule dependent. Perfluorohexyloctane was well tolerated with instillation site reactions below 3% in both treatment regimens.

The SEECASE study was conducted at 12 ophthalmology practices in the United States with patients who had a history of DED in both eyes and if one eye (the same eye) met the inclusion criteria at screening and at randomization time. 

Several symptom assessments such as eye dryness score measured using visual analog scale (VAS), VAS for other symptoms such as burning/stinging, itching, blurred vision, and sensitivity to light, and ocular surface disease index (OSDI) were evaluated to assess the effect of perfluorohexyloctane on DED symptomatology.

Patients treated with perfluorohexyloctane also experienced statistically significant improvement of certain DED symptoms over the entire duration of the Phase 2 study. Changes from baseline were statistically significant compared with those of the control group at week eight [P < 0.001 (QID) and P = 0.002 (BID)].

Other symptoms evaluated included burning/stinging, sticky feeling, foreign body sensation, itching, blurred vision, sensitivity to light and pain. 

The following treatment emergent adverse events (TEAEs) reported by more than 2% of subjects were blurred vision in the perfluorohexyloctane QID group, eye irritation in the perfluorohexyloctane BID group and eye pain in the saline group. 

Overall the number of patients reporting at least one TEAE was similar between the treatment groups.

"The results demonstrated in the SEECASE study support perfluorohexyloctane as a potential new treatment option for patients with DED associated with MGD, and we look forward to learning the results from both of the Phase 3 studies,” Christian Roesky, PhD and CEO of Novaliq GmbH, said in a statement.

In 2019, Bausch Health and Bausch + Lomb acquired an exclusive license for the commercialization and development of perfluorohexyloctane in the United States and Canada.

Bausch + Lomb has enrolled 599 participants in the first of two Phase 3 studies evaluating perfluorohexyloctane as a first-in-class investigational drug to treat the signs and symptoms of dry eye disease associated with meibomian gland dysfunction.

Enrollment completed for first Phase 3 study of perfluorohexyloctane

 developed by an Israeli company has been successfully implanted in the eye of a man who lost his sight a decade ago.

According to a release by CorNeat Vision, the 78-year-old patient regained his vision after the CorNeat KPro device was implanted into the eye.

The company said the implant replaces deformed, scarred or opacified corneas as it melds with the eye wall. The device is designed to integrate with ocular tissue using a patented synthetic non-degradable nanofabric skirt, which is placed under the conjunctiva.

The procedure was performed Jan. 11 by Professor Irit Bahar, the head of the ophthalmology department at Rabin Medical Center in Petah Tikva, Israel.

Following the procedure, the company reported that the patient was able to recognize his family and read words.

“The moment we took off the bandages was emotional and significant,” Dr. Bahar said in a statement. “Moments like these are the fulfillment of our calling as doctors. We are proud of being at the forefront of this exciting and meaningful project which will undoubtedly impact the lives of millions.”

In 2020, CorNeat Vision was granted approval to move forward with clinical trials of the artificial 

 on 10 patients who had corneal blindness.

Gilad Litvin, MD, CorNeat Vision's co-founder, chief medical officer, and the inventor of the CorNeat KPro, said in a statement that being in the room with the patient was a “surreal” experience.

"After years of hard work, seeing a colleague implant the CorNeat KPro with ease and witnessing a fellow human being regain his sight the following day was electrifying and emotionally moving, there were a lot of tears in the room,” Dr. Litvin said in the statement. “This is an extremely important milestone for CorNeat Vision, key in our journey to enable people around the world to fully enjoy their vision potential."

Almog Aley-Raz, CorNeat Vision's co-founder, CEO and vice president of research and development, noted in the statement that the implantation is the first step in a multi-national clinical trial, geared toward attaining CE Mark, FDA clearance and China NMPA approval.

Aley-Raz noted that a total of 10 patients are approved for the trial at Rabin Medical Center in Israel with 2 additional sites planned to open this January in Canada and 6 others at different stages in the approval process in France, the United States, and the Netherlands.

“Our first trial includes blind patients who are not suitable candidates for- or have failed one or more corneal transplantations,” Aley-Raz said in the statement. “Given the visual performance of our device, the expected healing time and retention, and the fact that it cannot carry disease, we plan to initiate a second study later this year with broader indications to approve our artificial cornea as a first line treatment, displacing the use of donor tissue used in full thickness corneal transplantations."

A device developed by an Israeli startup was implanted in the eye of a patient, enabling him to recognize his family and read words. 


David Hutton

Articles

Betamethasone 0.2% gets positive marks in Phase II trial for treatment of post-cataract surgery pain, inflammation

Enrollment completed for first Phase 3 study of perfluorohexyloctane

Artificial cornea restores patient’s vision

As COVID-19 focuses attention on vaccine, medication shortages loom