Sorry I haven’t posted for far too long, but I’m working on SEVERAL big projects that I will roll out in small segments including the conclusions to My B12 Journey and My Parathyroid Journey, both hopefully by the end of the year.
In the meantime, though, I received an unsolicited brochure in the mail from Apellis about their new drug for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD), and I just can’t pass this by without a comment.
This came in the US Mail and was addressed to my name. Not sure how they got my name and determined that I might be a potential customer. But a few guesses: Either of the 2 eye care clinics I’ve seen in the last few years. Maybe my health insurance company. Maybe Medicare. Perhaps a new health app I signed up for. Who knows, maybe even my employer: I work of a hospital.
Regardless, someone spilled the beans with my personal information. I certainly didn’t request it. But Apellis was glad to buy it.
So I thought I would reward them by sharing the publicly available information about their product, with my astute comments of course!
Here’s a link to their FDA Label and my comments below: SOURCE
Indications and Usage: “SYFOVRE is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).”
What is GA exactly? Here’s the short story: “Geographic atrophy (GA) is a chronic progressive degeneration of the macula, as part of late-stage age-related macular degeneration (AMD).” (SOURCE )
Here’s a little more information with HIGHLIGHTS by me: “Age-related macular degeneration (AMD) is a late-onset, neurodegenerative retinal disease that shares several clinical and pathological features with Alzheimer's disease (AD), including stress stimuli such as oxidative stress and inflammation.” ( SOURCE )
Mechanism of Action: “Pegcetacoplan binds to complement protein C3 and its activation fragment C3b with high affinity thereby regulating the cleavage of C3 and the generation of downstream effectors of complement activation”
This is always the first thing I look at on drugs. It often just says “ Mechanism of Action is unknown” or some such drivel. However, when it DOES state one, it can lead you to the real root cause of the disease.
But they did a really good job of making this one a muddy mess. I doubt that many scientists could actually understand this. They might as well have used the “Unknown” terminology. BUT, here’s the best I can simply put it:
“2. Biology of Complement System in Retina (SOURCE) including quotes below:
“The CS cascade is comprised of four activation pathways. All of the pathways ultimately end in the central cleavage of C3 factor and in the generation of its active fragments C3a and C3b. C3a is the anaphylatoxin that triggers a range of chemotactic and proinflammatory responses, such as recruitment of inflammatory cells and increased microvasculature permeability, whereas C3b is responsible for opsonization of foreign surfaces covalently attached to C3b (see Figure 1).”
As usual, I have found some correlation the Glutamate toxicity in this disease, which they continue to ignore while pointing to processes upstream or downstream:
Amino Acids Metabolism in Retinopathy: From Clinical and Basic Research Perspective ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781488/
Excepts below:
“The transcripts for CCL5, CEBPB, IL13RA2, IL15RA, IL6, IL8, and CXCL3 were up-regulated while the transcripts for C3, CCL2, IL11RA, and IL18 genes exhibited down-regulation.”
“It is reported that the increased level of glutamate in the retina will cause neurotoxic effects”
A few other things of note on the Label referenced above:
“6 ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
Ocular and periocular infections [see Contraindications (4.1)]
Active intraocular inflammation [see Contraindications (4.2)
Endophthalmitis and retinal detachments [see Warnings and Precautions (5.1)] Neovascular AMD [see Warnings and Precautions (5.2)]
Intraocular inflammation [see Warnings and Precautions (5.3)]
Increased intraocular pressure [see Warnings and Precautions (5.4)]”
WOW! What a list! Almost sounds dangerous.
6.1 Clinical Trials Experience
“Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.”
“Objects in the mirror may be closer than they appear”. Don’t you just love disclaimers to “Scientific” studies?
“13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Animal carcinogenicity studies of pegcetacoplan have not been conducted.”
Really? They haven’t tested this stuff for cancer???
There’s more, I’m sure, but I think I’ve covered enough for now.
See you next time.