Pre-Existing Allergy Toward Polyethylene Glycol (PEG) is Most Recent Causation Theory Offered by Apellis
(Posted by Tom Lamb at Drug Injury Watch)
In late January 2024, a leading medical journal for ophthalmologists and retina specialists, the Journal of VitreoRetinal Diseases, published this Syfovre case report, "Occlusive Retinal Vasculitis After a Single Injection of Pegcetacoplan", written by three authors affiliated with the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, in Miami, Florida.
Here is the Abstract for this Syfovre case report involving an 80-year-old woman who developed retinal vasculitis shortly after just one Syfovre (pegcetacoplan) injection:
Purpose: To describe a patient with retinal vasculitis after a single intravitreal injection (IVI) of [Syfovre (pegcetacoplan)].
Methods: A case and its findings were analyzed.
Results: An 80-year-old woman was treated with [Syfovre (pegcetacoplan)] for subfoveal geographic atrophy. Ten days later, the patient noted “purple iridescent waves” but did not immediately report it. On day 18, she presented with pain and decreased visual acuity from 20/80 (pinhole) preinjection to 20/150 postinjection. No signs of inflammation were observed, and she was treated for high intraocular pressure (30 mm Hg). On day 23, iritis was noted. The fluorescein angiogram showed severe occlusive vasculitis involving all quadrants and the macula. The vasculitis/neuroretinitis laboratory panels were negative, and no contributing systemic features were identified other than well-controlled diabetes.
Conclusions: In this patient, occlusive retinal vasculitis occurred shortly after a single IVI of [Syfovre (pegcetacoplan)].
About a month earlier, the Journal of VitreoRetinal Diseases (JVRD), which is the peer-reviewed journal of the American Society of Retina Specialists (ASRS), published a more general report on numerous Syfovre cases of retinal vasculitis, co-authored by members of the ASRS Research and Safety in Therapeutics (ReST) Committee. In summary, this report considered 14 eyes of 13 patients who developed retinal vasculitis after their first Syfovre injection. For this set of Syfovre case reports, the ASRS ReST report provided these findings:
- 11 eyes were diagnosed as having developed occlusive vasculitis after a Syfovre injection;
- 6 of 14 eyes had significant vision loss, having lost more than 6 lines of vision; and,
- 2 eyes required enucleation, a surgical procedure that involves the removal of the entire eye.
And from the Abstract for that December 2023 JVRD article, "Retinal Vasculitis After Intravitreal Pegcetacoplan: Report From the ASRS Research and Safety in Therapeutics (ReST) Committee":
Conclusions: There is currently no known etiology for vasculitis in this series. Optimum treatment strategies remain unknown. Infectious etiologies should be considered, and corticosteroid treatments may hasten resolution of inflammatory findings. Continued treatment of affected patients with [Syfovre (pegcetacoplan)] should be avoided.
A relatively minor correction, or "Corrigendum", was later issued to the ASRS Research and Safety in Therapeutics (ReST) Committee report, in February 2024, which read as follows:
The original sentence appeared as follows:
However, it is notable that [Syfovre (pegcetacoplan)] (and [Izervay (avacincaptad pegol)]) are synthetic PEGylated peptides and not biologically manufactured compounds.
The revised sentence now appears in the article as follows:
However, it is notable that [Syfovre (pegcetacoplan)] is a synthetic PEGylated peptide and not a biologically manufactured compound.
__________________________________________________________________
Syfovre
Free Case Evaluation
Strictly Confidential, No Obligation.
__________________________________________________________________
Whether related or not, we use that February 2024 JVRD ASRS ReST report article correction as our transition to pointing out the most recent explanation from Apellis Pharmaceuticals about the cause of Syfovre patients developing vasculitis.
Before we get there, however, we want to present this contextual information from a Wikipedia page about PEGylation in a pharmaceutical context:
PEGylation (or pegylation) is the process of both covalent and non-covalent attachment or amalgamation of polyethylene glycol (PEG, in pharmacy called macrogol) polymer chains to molecules and macrostructures, such as a drug, therapeutic protein or vesicle, which is then described as PEGylated. PEGylation affects the resulting derivatives or aggregates interactions, which typically slows down their coalescence and degradation as well as elimination in vivo. [Footnotes omitted.]
Now, from this February 28, 2024, Fierce Pharma news report, "Apellis cites current challenges with Syfovre launch but bright prospects in the long term", we get the most recent explanation from Apellis about the cause of Syfovre-related vasculitis:
As for Syfovre’s safety issue — which Apellis originally speculated was a needle problem for the injected drug — the company now “firmly” believes it is caused by a pre-existing allergy toward polyethylene glycol, Francois said. The incidence of users developing vasculitis remains at .01% per injection, the company said. [Emphasis added.]
Regarding the previous "causation" theory offered up by Apellis for a Syfovre case report involving retinal vasculitis, we take you back to this October 2023 article, "Apellis Updates Number of Syfovre Retinal Vasculitis Cases But Provides No Further 'Explanation' -- On That Aspect, in August 2023 Apellis Asked Doctors to Stop Using Syfovre Injection Kits With a 19-gauge Filter Needle".
Perhaps you know about a Syfovre case report and want to share your information. If so, we are most interested to hear from you and learn more about this (apparently) still-evolving Syfovre safety issue.
We are handling Syfovre drug injury lawsuits for patients who suffered vision loss due to vasculitis or vascular occlusion after a Syfovre injection. Those Syfovre lawsuits would be filed against Apellis Pharmaceuticals, not the patients' ophthalmologists or retina specialists.
DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects
Drug Injury Case Evaluation - Free. Confidential. No Obligation.