More on the “pipeline” & notice about some recalled drops, too.
First the good: “Global health care company Grifols has announced that the US Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application to initiate a phase 2 trial to assess its immunoglobulin (IG) drops (GRF312 ophthalmic solution) for the treatment of dry eye disease (DED).1 The drop has the potential to become the first-ever ocular surface indication for an IG, according to a news release.”
From https://www.optometrytimes.com/view/us-fda-clears-grifols-investigational-new-drug-application-for-immunoglobulin-drops-for-the-treatment-of-ded?ekey=RUtJRDoxMzc2NUY0My0zNkZDLTQ3MTAtQkM5Ny02NUMwQjkxNEYzNzk%3D&utm_campaign=emailname&utm_medium=email&_hsenc=p2ANqtz--W10iWBq4V7dpx4RuXUoNWCBcc8dlnPiFPwDNthnKXSU13up41XQYAf-zXxikJaTSKF8IRD9d9jfmTwllLnsIeu1KqQw&_hsmi=362995484&utm_source=hs
So what does this mean? Many of you suffering with autoimmune-related diseases are aware that Immunoglobulins (also known as antibodies, they are the basis for our immune response to body-invading “enemies,”) are complex proteins made by our body’s white blood cells known as plasma cells. Invaders such as bacteria and viruses along with certain cancers, have unique proteins called antigens, that become known to these plasma cells and trigger them to make the immunoglobulins. In certain autoimmune diseases such as rheumatoid arthritis, some cells produce a chemical known as TNF-alpha (Tumor Necrosis Factor). This is one of a group of chemicals made by the body termed cytokines, which in the case of TNF-alpha, can bind to other cells and trigger an immune response leading to inflammation. Immunoglobulins targeted to TNF-alpha can neutralize or “block” it and prevent this inflammation.
Many of my patients with severe forms of inflammation - especially when autoimmune related, have ended up on so-called iVIG - or intravenous immunoglobulin therapy. This has been sight saving in many cases and life saving, in some. The idea of applying immunoglobulins directly to the surface of the eye seems a small but significant leap towards helping those with autoimmune surface problems.
It is also true that our immune system is a bit like a finely tuned race car’s engine, in the sense that minor things can get it running roughly, and take away its ability to effectively keep us out of trouble with germs and cancers. Immunoglobulins can help put this engine “back in tune.” At this stage, I’m not sure what kind of antibodies and which pathways will be targeted by this new eye drop, but I’m excited to see pharma companies begin to use this novel technology to help dry eye sufferers.
Topical Immunotherapy is not totally new to ocular surface treatments, as Interferon (a natural chemical produced in the body to help fight viral infections and cancer-producing mutations by signaling the immune system to attack these “intruders”) has been used for many years to treat ocular surface squamous neoplasias (OSSN are cancerous growths on the surface and commonly affecting the cornea). Because many (if not all) sufferers of dry eye disease have an inflammation-related component, the is great potential for this new group of medications! Phase two is a significant, necessary step towards possible FDA clearance for prescriptive use - and further testing will be necessary before it becomes commercially available.
MORE GOOD and EVEN MORE PROMISING news - is the recent FDA approval for a new dry eye medication, acoltremon ophthalmic solution 0.003%, which should hit the pharmacies as “Tryptyr,” soon!
”Alcon announced that the FDA has approved acoltremon ophthalmic solution 0.003%, a first-in-class transient receptor potential melastatin 8 (TRPM8) receptor agonist, for the treatment of the signs and symptoms of dry eye disease (DED). The drop, previously known as AR-15512, will be sold under the name Tryptyr. The neuromodulator stimulates corneal sensory nerves to increase natural tear production rapidly following instillation.1” This triggers the corneal nerves that sense cooling from menthol and sense a signal to the tear producing glands and cells responsible for making the tears I call the “sprinkler system” - the best water, salt, protein and oil form of tears that I call the “salad dressing.” It seems that this would be similar to the tears produced by neurostimulation from products like the old “TrueTear”, the newer iTear and nasal spray in the form of Tyrvaya. Since it has yet to be available in pharmacies, and is still in the early “rolling out” phase, I can’t comment on more specifics than to say that Japan has had menthol-type, artificial tear products available for some time and menthol can be found in some current over the counter tear drops - so by targeting the exact mechanism by which menthol works, it seems likely this will be a significant step forward. (Above quote and following quote excerpted from the link below article): “The approval is supported by 2 phase 3 clinical trials, COMET-2 and COMET-3, that evaluated more than 930 patients with a history of DED.3 In the trials, 4 times more Tryptyr patients experienced at least a 10-mm increase in natural tear production at day 14 when compared to vehicle. COMET-2 saw 42.6% vs 8.2% of patients with at least a 10-mm increase, and COMET-3 saw 53.2% vs 14.4% (both P < .0001). Additionally, it was noted that Tryptyr demonstrated a statistically significant natural tear production as early as day 1. Acoltremon was well tolerated in the studies, and no serious ocular adverse events were reported.”
from: https://www.optometrytimes.com/view/fda-approves-alcon-s-tryptyr-ar-15512-for-signs-and-symptoms-of-dry-eye-disease?ekey=RUtJRDoxMzc2NUY0My0zNkZDLTQ3MTAtQkM5Ny02NUMwQjkxNEYzNzk%3D&utm_campaign=emailname&utm_medium=email&_hsenc=p2ANqtz-_mTaVg9x1wV-ZRbNGFInsS9QC9SsB0S9K4Wp5pgXHpK7mb9HbZl750rN_uLXgBCkNpT4EUoVKVqmgl367EqTmJpZewIQ&_hsmi=364094868&utm_source=hs
NOW SOME BAD NEWS:
“BRS Analytical Services, LLC, has initiated a voluntary recall at the consumer level of five different ophthalmic products due to potential quality concerns. The move was made by its distributor AvKARE.
First thing’s first: Which products are these?
In its recall notice, BRS identified the following:
AvKARE Artificial Tears Ophthalmic Solution
AvKARE Carboxymethylcellulose Sodium Ophthalmic Gel 1%
AvKARE Carboxymethylcellulose Sodium Ophthalmic Solution
AvKARE Lubricant Eye Drops Solution
AvKARE Polyvinyl Alcohol Ophthalmic Solution
In total: This reportedly accounts for nearly 75,000 individual products distributed across the U.S., though specific stores or states were not identified. See here for expiration dates.
What does ‘consumer level’ mean?
This type of recall is considered the most extensive, as it entails the removal of all products from all points in the supply chain—from the manufacturer to, most importantly, consumers.
And what led to its initiation?
Per AvKARE, the move was made due to “manufacturing cGMP (Current Good Manufacturing Practice) deviations” uncovered during a recent FDA audit. More details on that here.
And what’s the concern in this recall situation?
Keep in mind: The concerns identified in this case were done so by the FDA itself. While AvKARE noted that the current “health hazard to [users] is unknown,” these cGMP deviations could potentially “lead to products of unacceptable quality.”
As such: “It is not possible to rule out patient risks resulting from these products,” the distributor stated.
Speaking of risks … any reports of adverse events?
So far? No, AvKARE did not address any specific instances.
And if I need to report an adverse event?
Submit a form online via the FDA’s MedWatch Adverse Event Reporting program or by mail/fax.
What should I do if I have some of these products in my inventory?
The supplier asks consumers and eyecare providers to immediately discontinue use and remove from active inventory. For these customers, AvKARE is requesting they complete a Quantity to Return section and a customer information page, accessible here.”
From: https://emails.eyesoneyecare.com/more-eye-drop-recall?ecid=ACsprvtk0uapl0jZQE-1VEV_EG-noC8D4bONg1Nm5-_Exo2dHoq06FRYILHm6uYzJilHMkH6FFyL&utm_campaign=%5Bglance-marketing%5D%20weekly%20ophthalmology%20newsletter&utm_medium=email&_hsenc=p2ANqtz-9Lljcj4EBnsWflVQdAXCxckL4v4quMNrGm_wmbd4QVVh2nHccg52ou7Qlh9sOu0JDTZ0_Zb-ZMDibF-EkjWxgXuID4Pg&_hsmi=361655586&utm_content=361655586&utm_source=hs_email
To schedule an appointment with Dr. Jaccoma, call Excellent Vision at either of these two dry eye offices:
(1) 155 Griffin Rd, Portsmouth, NH 03801 (603) 574-2020
(2) 3 Woodland Rd, STE 112 Stoneham, MA 02180 (near Boston) (781) 321-6463