Watch to discover more
about SYFOVRE

SYFOVRE MOA

INDICATION

SYFOVRE^® (pegcetacoplan injection) is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Please stay tuned for additional Important Safety Information and please see accompanying full Prescribing Information.

In geographic atrophy, time is of the essence.

In the United States, one million people suffer from this advanced form of dry age-related macular degeneration.

Overactivation of the complement system is strongly associated with the progression of GA.

C3 is the central protein in the complement cascade. When C3 is overactivated, it unleashes negative effects downstream, like inflammation, phagocytosis, and cell membrane disruption. All of which are thought to contribute to retinal cell death.

SYFOVRE is the first approved treatment for GA secondary to AMD.

SYFOVRE is a synthetic peptide-based inhibitor of C3: two cyclic peptides linked by a polyethylene glycol chain.

SYFOVRE acts on the central protein in the complement cascade to help regulate complement overactivation. SYFOVRE binds to C3 and its activation fragment C3b with high affinity, regulating the cleavage of C3 and the generation of downstream effectors of complement activation.

By targeting C3 and C3b, SYFOVRE can slow the downstream effectors of complement overactivation.

For patients with GA, the time for treatment is now.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

• SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation

WARNINGS AND PRECAUTIONS

• Endophthalmitis and Retinal Detachments
  • Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering SYFOVRE to minimize the risk of endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.
• Retinal Vasculitis and/or Retinal Vascular Occlusion
  • Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of SYFOVRE. Cases may occur with the first dose of SYFOVRE and may result in severe vision loss. Discontinue treatment with SYFOVRE in patients who develop these events. Patients should be instructed to report any change in vision without delay.
• Neovascular AMD
  • In clinical trials, use of SYFOVRE was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24. Patients receiving SYFOVRE should be monitored for signs of neovascular AMD. In case anti-Vascular Endothelial Growth Factor (anti-VEGF) is required, it should be given separately from SYFOVRE administration.
• Intraocular Inflammation
  • In clinical trials, use of SYFOVRE was associated with episodes of intraocular inflammation including: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare. After inflammation resolves, patients may resume treatment with SYFOVRE.
• Increased Intraocular Pressure
  • Acute increase in IOP may occur within minutes of any intravitreal injection, including with SYFOVRE. Perfusion of the optic nerve head should be monitored following the injection and managed as needed.

ADVERSE REACTIONS

• Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, conjunctival hemorrhage.

Please see accompanying full Prescribing Information.

The Safety Profile of SYFOVRE

VO:

SYFOVRE is a complement inhibitor indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation. We will cover additional Important Safety Information for SYFOVRE later in this video.

Dr Singh:

So, I'm going to get into the safety of this drug from the studies that we've seen from both OAKS and DERBY.

In this chart, you see the events reported in 2% or more of patients at 24 months in both OAKS and DERBY. In total, 839 patients were exposed to SYFOVRE, and 417 to sham. And the most common adverse events were ocular discomfort, neovascular AMD, vitreous floaters, and conjunctival hemorrhage. ION was reported in 1.7% of patients treated monthly; 0.2% of patients treated every-other-month; and none of the patients assigned to the sham treatment. There were a total of 8 total events of ION -- 7 in the monthly; 1 in the every-other-month arm; and 0 in the sham arm. 3 of these were serious adverse events, as previously reported, and 5 events were not classified as serious adverse events. All the patients who developed ION had a disc-at-risk and other comorbidities. The rates and cause of death were consistent with the elderly populations within these studies.

Here we note the rates of inflammation for both OAKS and DERBY. At 24 months, a cumulative case reported were 28 in total, for a rate of .24% per injection. This is over 11,736 injections total, which were administered over the 24 months of both of these trials. The total number of cases included 4 cases, in this report in 2018, which were linked to a drug impurity. The trial was halted, and the trial was then restarted when the drug impurity was removed. No cases of retinitis or vasculitis, either occlusive or nonocclusive, were reported during the course of these studies.

Dr Goldberg:

A lot of those adverse events are things that we expect with intravitreal drug delivery; we know we've got to use proper aseptic technique to minimize many of those complications.

And then, specifically around inflammation, I found it heartening that there were no cases of retinal vasculitis or occlusive vasculitis, and that once the inflammation died down patients were able to resume treatment with SYFOVRE.

Dr Wykoff:

An important question, because we do know that there's an increased rate of wet AMD development with SYFOVRE treatment. This appeared dose-dependent, with a higher rate in the monthly arm compared to the every-other-month arm. Important that both patients and physicians are aware of this; patients need to understand that this is a risk, and if they do develop this they may need to be treated with both SYFOVRE and an anti- VEGF therapeutic, as was done in the Phase 3 program.

From a physician perspective, really important that we are examining these patients thoroughly when we see them, and also that we are comprehensively imaging them -- for example, with OCT; and it's important that when you obtain an OCT regularly in these patients, to look at the entire volume scan. We saw this repeatedly in the clinical trial where sometimes there would be subtle signs of exudation; and important to make sure that we're catching these transitions to wet AMD early so they can be treated appropriately.

INDICATION

SYFOVRE^® (pegcetacoplan injection) is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

• SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation

WARNINGS AND PRECAUTIONS

• Endophthalmitis and Retinal Detachments
  • Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering SYFOVRE to minimize the risk of endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.
• Retinal Vasculitis and/or Retinal Vascular Occlusion
  • Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of SYFOVRE. Cases may occur with the first dose of SYFOVRE and may result in severe vision loss. Discontinue treatment with SYFOVRE in patients who develop these events. Patients should be instructed to report any change in vision without delay.
• Neovascular AMD
  • In clinical trials, use of SYFOVRE was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24. Patients receiving SYFOVRE should be monitored for signs of neovascular AMD. In case anti-Vascular Endothelial Growth Factor (anti-VEGF) is required, it should be given separately from SYFOVRE administration.
• Intraocular Inflammation
  • In clinical trials, use of SYFOVRE was associated with episodes of intraocular inflammation including: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare. After inflammation resolves, patients may resume treatment with SYFOVRE.
• Increased Intraocular Pressure
  • Acute increase in IOP may occur within minutes of any intravitreal injection, including with SYFOVRE. Perfusion of the optic nerve head should be monitored following the injection and managed as needed.

ADVERSE REACTIONS

• Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, conjunctival hemorrhage.

Please see accompanying full Prescribing Information.

The Efficacy Data for SYFOVRE

VO:

SYFOVRE is a complement inhibitor indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation We will cover additional Important Safety Information for SYFOVRE later in this video.

Dr Wykoff:

So, as you're all aware, OAKS and DERBY were two global Phase 3 clinical trials. They were designed to evaluate the efficacy and safety of SYFOVRE over 24 months.

1,258 patients with geographic atrophy secondary to AMD were randomized in a 2:2:1:1 fashion in this double-masked program. 420 patients were enrolled with every-other-month SYFOVRE dosing; 419 patients with every-month SYFOVRE dosing; and then 211 and 208 with sham every-other-month and monthly dosing respectively.

The key trial assessment was change from baseline in rate of geographic atrophy lesion area growth in mm² as measured by fundus autofluorescence, with a total trial duration of 24 months.

DERBY and OAKS were designed to enroll a broad range of patients, and this is meant to be representative of clinical practice with patients with geographic atrophy.

Now looking specifically at the efficacy data. In these data, SYFOVRE achieved continuous reductions in lesion growth rate through Month 24; and breaking this graph down on the X axis we see time and months through 24 months with four 6-month intervals; and on the Y axis we see mean rate of change from baseline in geographic atrophy lesion area.

And cumulatively here through 2 years, we saw an 18 and 22% reduction in GA lesion growth with SYFOVRE treatment compared to baseline. This analysis is based on a mixed-effects model for repeated measures, assuming a piecewise linear trend in time with knots at the 6, 12, and 18 timepoints.

Looking now at a similar data depiction here from DERBY, again, in this similar Phase 3 clinical trial, SYFOVRE achieved continuous reductions in lesion growth rate through Month 24 -- the same set-up here with the graph, time on the X axis, and change in lesion area on the Y axis. Here you see cumulatively a 17 and 18% reduction in GA lesion growth with every-other-month and monthly dosing, respectively, compared to sham.

Looking now at the combined data set of OAKS and DERBY data sets put together, SYFOVRE again, slowed geographic atrophy progression. And the key finding here is that there was an increasing treatment effect over time, such that over 2 years those proportions of reduction in GA lesion growth were 17 and 20% with every-other-month and monthly dosing.

But now, if we look at the individual 6-month segments, you can see an increasing treatment effect. For example, with monthly dosing, you see that increasing from 13 to 19 to 20, and then to 30% in the 1st, 2nd, 3rd, and 4th 6-month intervals over time.

The combined piecewise linear analysis here did not a prespecified statistical procedure controlling for the type 1 error.

VO:

INDICATION

SYFOVRE^® (pegcetacoplan injection) is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

• SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation

WARNINGS AND PRECAUTIONS

• Endophthalmitis and Retinal Detachments
  • Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering SYFOVRE to minimize the risk of endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.
• Retinal Vasculitis and/or Retinal Vascular Occlusion
  • Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of SYFOVRE. Cases may occur with the first dose of SYFOVRE and may result in severe vision loss. Discontinue treatment with SYFOVRE in patients who develop these events. Patients should be instructed to report any change in vision without delay.
• Neovascular AMD
  • In clinical trials, use of SYFOVRE was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24. Patients receiving SYFOVRE should be monitored for signs of neovascular AMD. In case anti-Vascular Endothelial Growth Factor (anti-VEGF) is required, it should be given separately from SYFOVRE administration.
• Intraocular Inflammation
  • In clinical trials, use of SYFOVRE was associated with episodes of intraocular inflammation including: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare. After inflammation resolves, patients may resume treatment with SYFOVRE.
• Increased Intraocular Pressure
  • Acute increase in IOP may occur within minutes of any intravitreal injection, including with SYFOVRE. Perfusion of the optic nerve head should be monitored following the injection and managed as needed.

ADVERSE REACTIONS

• Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, conjunctival hemorrhage.

Please see accompanying full Prescribing Information.

Appropriate Patients for SYFOVRE

VO:

SYFOVRE is a complement inhibitor indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation. We will cover additional Important Safety Information for SYFOVRE later in this video.

Dr Goldberg:

Great question, and I've actually already started to have those conversations.

And I can tell you, the conversation is so different than what it used to be because now we're able to offer hope when we talk about, "You have this relentless progressive disease," and we now have a treatment for it -- a treatment that doesn't reverse the GA that's already taken place, but it does slow the progression of the geographic atrophy.

Dr. Singh:

And I think for us the conversation is going to be very tailored to that individual. As we did with anti-VEGF therapy, we personalize that approach. We talk to them about the benefits of the therapy and what's involved in the treatment process; and some of them would like to maybe choose a different option for treatment. Whether it's one eye or both eyes, they're going to make that decision with an informed physician who's going to help guide that kind of tailored treatment approach.

Dr. Wykoff:

I think a key to communication here is setting patient expectations. As some of these patients have lost so much function over time, it needs to be clear that we're not reversing the disease here, and we're not stopping it, but we are meaningfully slowing this down.

Dr Singh:

We're going to use a lot of the clinical trial inclusion/exclusion criteria from OAKS and DERBY to help us initially with the determination of who's eligible for this treatment. And we know that and obviously in this trial that they enrolled a very heterogeneous population, both with foveal and non-foveal geographic atrophy, so it's very flexible and helps us identify and treat those patients and talk about the benefits in both populations. And I see patients, really, who have lost vision with advanced disease in one eye, where they have neovascularization or advanced center-involving geographic atrophy and have lost vision, where they're motivated to keep their fellow eye from having this condition approach.

VO:

INDICATION

SYFOVRE^® (pegcetacoplan injection) is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

• SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation

WARNINGS AND PRECAUTIONS

• Endophthalmitis and Retinal Detachments
  • Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering SYFOVRE to minimize the risk of endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.
• Retinal Vasculitis and/or Retinal Vascular Occlusion
  • Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of SYFOVRE. Cases may occur with the first dose of SYFOVRE and may result in severe vision loss. Discontinue treatment with SYFOVRE in patients who develop these events. Patients should be instructed to report any change in vision without delay.
• Neovascular AMD
  • In clinical trials, use of SYFOVRE was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24. Patients receiving SYFOVRE should be monitored for signs of neovascular AMD. In case anti-Vascular Endothelial Growth Factor (anti-VEGF) is required, it should be given separately from SYFOVRE administration.
• Intraocular Inflammation
  • In clinical trials, use of SYFOVRE was associated with episodes of intraocular inflammation including: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare. After inflammation resolves, patients may resume treatment with SYFOVRE.
• Increased Intraocular Pressure
  • Acute increase in IOP may occur within minutes of any intravitreal injection, including with SYFOVRE. Perfusion of the optic nerve head should be monitored following the injection and managed as needed.

ADVERSE REACTIONS

• Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, conjunctival hemorrhage.

Please see accompanying full Prescribing Information.

SYFOVRE Dosing and Administration

VO:

SYFOVRE is a complement inhibitor indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation. We will cover additional Important Safety Information for SYFOVRE later in this video.

Dr Goldberg:

In clinical trials, patients were treated either monthly or every-other-month, and the label actually provides for that flexible dosing schedule, allowing for treatment once every 25 to 60 days.

SYFOVRE is available for order now. It comes in a carton, as you see pictured here…

…and in that carton is the glass vial containing SYFOVRE. When you order SYFOVRE…

…it also comes with an injection kit.

In that injection kit is a sterile 5- micron filter needle, as well as a ½” 29-gauge thin-walled injection needle with a Luer-lock hub. Because of its viscosity, it’s important to use a 1 mL Luer-lock syringe, and this medicine is injected 0.1 mL is the appropriate dose.

Dr Wykoff:

This is a great data set from OAKS and DERBY because we have data for 2 different dosing frequencies, and the package insert, as Roger beautifully laid out, is flexible to where we can treat people monthly or every other month. And so, I think this is a going to be a patient specific discussion. We've seen that there's efficacy with both monthly and every-other-month dosing. We've also seen some safety signals that may be slightly different between monthly and every-other-month dosing. It's really important that patients are informed of both the risks and benefits of both, and then I'd be happy to use it in either way, monthly or every-other-month dosing.

Dr Singh:

You know, in large academic organizations like ours, we have a formulary approval process, and we're going through that already. We've already started hearing from our patients, who are very interested after learning about the results of the study, and obviously wanting a therapy for so long in this unmet need.

And we've also had these discussions with our retina specialists who are trying to decide how they're going to incorporate this within their practice.

Dr Goldberg:

I'd say in the private practice setting, Rishi, it's pretty similar. We don't have to deal with a formulary, of course; we do have to deal with insurance companies and making sure all the authorizations are in place. But we've actually already begun to incorporate SYFOVRE into our workflows.

Dr Wykoff:

I think a key with incorporation here is that in contrast to a new-onset wet AMD patient, for example, where there really is immediacy -- you need to treat within days, ideally -- while this is not a slowly progressing disease in the way we thought of it traditionally, it's also not rapid. So, there is time. I'm having lots of conversations with patients; I'm giving them printouts; I'm giving them data to think about, about the safety and efficacy. And I really want patient engagement before initiating therapy, because this is a long-term commitment for patients; you really begin to get the benefit over many months to years of therapy. I want to make sure that they're committed to that long-term treatment before initiation.

VO:

INDICATION

SYFOVRE^® (pegcetacoplan injection) is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

• SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation

WARNINGS AND PRECAUTIONS

• Endophthalmitis and Retinal Detachments
  • Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering SYFOVRE to minimize the risk of endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.
• Retinal Vasculitis and/or Retinal Vascular Occlusion
  • Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of SYFOVRE. Cases may occur with the first dose of SYFOVRE and may result in severe vision loss. Discontinue treatment with SYFOVRE in patients who develop these events. Patients should be instructed to report any change in vision without delay.
• Neovascular AMD
  • In clinical trials, use of SYFOVRE was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24. Patients receiving SYFOVRE should be monitored for signs of neovascular AMD. In case anti-Vascular Endothelial Growth Factor (anti-VEGF) is required, it should be given separately from SYFOVRE administration.
• Intraocular Inflammation
  • In clinical trials, use of SYFOVRE was associated with episodes of intraocular inflammation including: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare. After inflammation resolves, patients may resume treatment with SYFOVRE.
• Increased Intraocular Pressure
  • Acute increase in IOP may occur within minutes of any intravitreal injection, including with SYFOVRE. Perfusion of the optic nerve head should be monitored following the injection and managed as needed.

ADVERSE REACTIONS

• Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, conjunctival hemorrhage.

Please see accompanying full Prescribing Information.

A Real-World Geographic Atrophy Case: Patient with CNV in the Fellow Eye

VO:

SYFOVRE is a complement inhibitor indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation. We will cover additional Important Safety Information for SYFOVRE later in this video.

Dr Goldberg:

This first one is a 74-year-old gentleman who is still quite active; he actually works as a stock broker. And he came to see me in 2021, referred for new-onset wet AMD in the right eye, which you can see here, with a hemorrhagic pigment epithelial detachment, subretinal hemorrhage and SHRM, as well as intraretinal fluid. That's in the right eye.

In the left eye we see drusen, and a small area of atrophy just temporal to the fovea. The vision in the left eye was 20/30; the vision in the right eye 20/150.

Well, after 2 years of treatment for the wet AMD in the fellow eye, unfortunately that eye had declined to count-fingers vision, and you can see here there's extensive RPE scarring and atrophy.

What happened in the left eye over those 2 years? Well, we see clearly documented growth of geographic atrophy. You can see it both on the fundus autofluorescence on the left just temporal to the fovea, as well as on the OCT with that hypertransmission defect. And this patient was complaining to me, although the vision was still 20/30, was noting that the quality of the vision was declining in the left eye, and we elected to treat that left eye with SYFOVRE.

Dr Singh:

That's a great case, because it really shows a difference in the OCT and the fundus autofluorescence in picking up the geographic atrophy. I don't think I would have appreciated that much atrophy that was present in this patient just by looking at that initial OCT, especially in light of the good vision that was present there.

Dr. Wykoff:

It's also a great case, because this is an example of how geographic atrophy can be such a broad spectrum of phenotypes. This case would not have actually qualified for the Phase 3 clinical trials. That lesion size is substantially smaller than a disc area. And yet, we see patients like this all the time in clinic, and especially when they have lost one eye already, many patients are very sensitive to visual decline in an eye like this, and they may be very interested in something that will slow the progression of disease in this eye.

Dr Goldberg:

In particular I think in this case, although it's small, it is fovea encroaching, and so to my mind I thought this was a pretty clear case, and the patient had actually been following the data very closely and was excited to initiate treatment.

VO:

INDICATION

SYFOVRE^® (pegcetacoplan injection) is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

• SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation

WARNINGS AND PRECAUTIONS

• Endophthalmitis and Retinal Detachments
  • Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering SYFOVRE to minimize the risk of endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.
• Retinal Vasculitis and/or Retinal Vascular Occlusion
  • Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of SYFOVRE. Cases may occur with the first dose of SYFOVRE and may result in severe vision loss. Discontinue treatment with SYFOVRE in patients who develop these events. Patients should be instructed to report any change in vision without delay.
• Neovascular AMD
  • In clinical trials, use of SYFOVRE was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24. Patients receiving SYFOVRE should be monitored for signs of neovascular AMD. In case anti-Vascular Endothelial Growth Factor (anti-VEGF) is required, it should be given separately from SYFOVRE administration.
• Intraocular Inflammation
  • In clinical trials, use of SYFOVRE was associated with episodes of intraocular inflammation including: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare. After inflammation resolves, patients may resume treatment with SYFOVRE.
• Increased Intraocular Pressure
  • Acute increase in IOP may occur within minutes of any intravitreal injection, including with SYFOVRE. Perfusion of the optic nerve head should be monitored following the injection and managed as needed.

ADVERSE REACTIONS

• Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, conjunctival hemorrhage.

Please see accompanying full Prescribing Information.

A Real-World Geographic Atrophy Case: Patient with Bilateral GA

VO:

SYFOVRE is a complement inhibitor indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation. We will cover additional Important Safety Information for SYFOVRE later in this video.

Dr Goldberg:

This is actually a 90-year-old woman with bilateral foveal-involving GA. The right eye, which is shown here, was more advanced -- actually had a 20/150 vision. Sometimes it's hard to predict what the visual acuity will be. But she was 20/150 in this right eye. And in the left eye, despite this extensive geographic atrophy, that to my eye is kind of involving the foveal center, but may have a couple photoreceptors left there. She's actually 20/60 in this left eye, and you can see that hyperautofluorescence around it. And so, we initiated to treat. We actually decided to treat the right eye -- the worse-seeing right eye first, with a plan to kind of alternate seeing her every month but treating each eye every other month.

Dr Wykoff:

This is a great case also. To me, this really brings out the concept of foveal involvement. I think, hypothetically and theoretically, we as clinicians think of, "I want to really find those patients with preserved foveal tissue to protect that over time." But in fact, many patients with foveal-involved GA can still have significant visual function, and again, they might be very interested in a treatment that could slow the progression of this disease by preserving more tissue over time

Dr Singh:

This case also demonstrates 2 important features of advancing disease. First is lesion size, which we know larger lesions progress faster. And the second was the hyperautofluorescent rim around both of those, the GA lesions in her bilateral picture. That also has a higher risk of progression in this patient.

Dr Wykoff:

I think the short answer there is that, no, I will not need to see documented growth of GA in the natural history of a given eye before I initiate therapy. The more nuanced answer, though, is it's very patient-specific. We know there are certain lesion types, for example, of regressed area of CNV that may have an atrophic footprint that may not progress over time. And that's why I think the autofluorescence in cases like that can be very helpful. Because there were very specific autofluorescence patterns that were required to be enrolled in DERBY and OAKS, I think it's important that we consider those, seeing that there's at least some hyperautofluorescence in the zone around the atrophy to suggest that this medication will be appropriate.

In a context like that, where there's clear hyperautofluorescence around the area of geographic atrophy that looks consistent with a diagnosis of GA secondary to AMD, I'll have a discussion about the safety and efficacy results of the trial with the patient, and then be happy to initiate therapy as soon as a patient feels like that's appropriate.

VO:

INDICATION

SYFOVRE^® (pegcetacoplan injection) is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

• SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation

WARNINGS AND PRECAUTIONS

• Endophthalmitis and Retinal Detachments
  • Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering SYFOVRE to minimize the risk of endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.
• Retinal Vasculitis and/or Retinal Vascular Occlusion
  • Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of SYFOVRE. Cases may occur with the first dose of SYFOVRE and may result in severe vision loss. Discontinue treatment with SYFOVRE in patients who develop these events. Patients should be instructed to report any change in vision without delay.
• Neovascular AMD
  • In clinical trials, use of SYFOVRE was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24. Patients receiving SYFOVRE should be monitored for signs of neovascular AMD. In case anti-Vascular Endothelial Growth Factor (anti-VEGF) is required, it should be given separately from SYFOVRE administration.
• Intraocular Inflammation
  • In clinical trials, use of SYFOVRE was associated with episodes of intraocular inflammation including: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare. After inflammation resolves, patients may resume treatment with SYFOVRE.
• Increased Intraocular Pressure
  • Acute increase in IOP may occur within minutes of any intravitreal injection, including with SYFOVRE. Perfusion of the optic nerve head should be monitored following the injection and managed as needed.

ADVERSE REACTIONS

• Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, conjunctival hemorrhage.

Please see accompanying full Prescribing Information.