Faricimab will be the first and only FDA-approved medicine targeting two distinct pathways, Ang-2 and VEGF-A, involved in retinal diseases and may cause vision loss. To see the Angiogenesis Foundation’s educational resources on Ang-2, please visit The Science of Ang-2.

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The FDA on Friday gave its approval to faricimab (Vabysmo, Genentech) for the treatment of wet age-related macular degeneration (AMD) and diabetic macular edema (DME).

Faricimab, a bispecific monoclonal antibody, is now the first and only FDA-approved drug to target two distinct pathways, Ang-2 and VEGF-A, that often cause retinal disease that may lead to vision loss. In preclinical studies, blocking angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF-A) reduced the vascular leakage/neovascularization, inflammation, and fibrosis.

Faricimab will be available in the United States in the coming weeks.

Genentech also submitted a Marketing Authorization Application for faricimab for the treatment of nAMD and DME, which the European Medicines Agency has accepted.¹

“Vabysmo represents an important step forward for ophthalmology. It is the first bispecific antibody approved for the eye and a major advance in treating retinal conditions such as wet AMD and diabetic macular edema,” Charles Wykoff, MD, PhD, director of research at Retina Consultants of Texas in Houston and a faricimab Phase III investigator, said in a statement. “With Vabysmo, we now have the opportunity to offer patients a medicine that could improve their vision, potentially lowering treatment burden with fewer injections over time.”

According to the news release, the approval is based on positive results across four Phase III studies in wet AMD and DME. The studies consistently showed that patients treated with Vabysmo given at intervals of up to four months achieved non-inferior vision gains versus aflibercept given every two months in the first year. Vabysmo was generally well tolerated in all four studies, with a favorable benefit-risk profile. The most common adverse reaction (≥5%) reported in patients receiving Vabysmo was conjunctival hemorrhage (7%).

In the release, Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, faricimab “provides a new approach to treating vision-threatening retinal conditions through a mechanism of action that targets two pathways simultaneously.”

“This is our second FDA approval in ophthalmology in recent months, underscoring our commitment to people living with retinal conditions,” he added in the statement.

Genentech also submitted a Marketing Authorization Application for faricimab for the treatment of nAMD and DME, which the European Medicines Agency has accepted.¹

In the studies conducted, about half of eligible individuals on faricimab were able to go 4 months between treatments within the first year, and up to three-quarters could go 3 months or longer in the TENAYA and LUCERNE nAMD studies and the YOSEMITE and RHINE DME studies.

Currently, the standard of care for these conditions requires eye injections as often as once every month.

For retina specialists, the approval is welcome news and offers a new treatment option for patients.

Lawrence Singerman, MD, FACS, of Retina Associates of Cleveland and a clinical professor of ophthalmology at Case Western Reserve University and Bascom Palmer Eye Institute, said he has been anticipating the announcement of FDA approval for faricimab.

“After giving presentations of data from the studies, and witnessing those presented by other investigators It is clear to me that this drug offers impressive efficacy and extended duration of action combined with an excellent safety profile,” he said. “This drug should ease the treatment burden on our patients with Wet AMD and DME.”

“The forthcoming availability of faricimab is a refreshing way to kick off 2022 for retina specialists and patients with macular disease alike,” said Andrew A. Moshfeghi, MD, MBA, associate professor of ophthalmology, University of Southern California.

Moshfeghi noted that faricimab appears to offer patients the chance to have more robust control of their macular disease and the potential for a longer treatment benefit.

“Having a new therapy for which approximately half of patients were able to be safely treated as infrequently as every 4 months is a big step forward for patients with chronic macular diseases like nAMD and DME—common conditions that traditionally require very frequent injections (every 1 to 2 months) with standard anti-VEGF monotherapy alone,” he said.

“I think the landscape for faricimab could be an exciting one for both exudative neovascular age-related macular degeneration and diabetic macular edema, particularly with sustaining and extending therapy for patients currently requiring high injection frequency,” said Mark P. Breazzano, MD, an assistant professor of ophthalmology at Wilmer Eye Institute, Retina Division, Johns Hopkins School of Medicine. “The data appear to show efficacy and durability with four-month treatment intervals for many of these patients. However, like any new treatment, it remains important to be cautious and continue monitoring for any safety signals that may follow FDA approval.”

According to Ian C. Han, MD, an associate professor, Institute for Vision Research, Ophthalmology and Visual Sciences, University of Iowa Hospital and Clinics, even with available treatment options, some patients reach a plateau of response to treatment with currently available agents, and the need for frequent office visits for injections continues to be a substantial burden, one that has only been exacerbated with the challenges of the pandemic.

“The current injectable medications on the market target vascular endothelial growth factor (VEGF), which plays a primary role in new blood vessel growth,” he said. “However, we have known for a while now that VEGF levels can modulate over time, and plenty of other factors beyond VEGF play a role in blood vessel formation and stabilization.”

Han noted that faricimab is the first FDA-approved agent to target not only VEGF but the angiopoietin (Ang) and Tie receptor pathway, which plays an important role in vascular stability and permeability.

Identical large, international, multicenter phase 3 trials for both wet AMD (LUCERNE/TENAYA) and DME (YOSEMITE/RHINE) compared faricimab to an available standard care treatment (aflibercept) and demonstrated that the majority of patients could be treated every 3 months or longer, with intervals up to 4 months included in the studies.

“Faricimab has the potential to decrease the treatment burden for patients with two conditions that we see the most (wet AMD and DME). It also represents an important step in moving beyond “just anti-VEGF” for treatment of these conditions, potentially paving the way for other drugs in the pipeline,” Han said. “As always with a new drug, ophthalmologists will need to translate the protocols from clinical trials to their everyday practice, including the varying treatment schedules (between one to four months in the phase 3 studies).”

Han added FDA-approval is a necessary and important step to bringing a new treatment to clinic.

“As we have recently been reminded, clinicians will need to evaluate the efficacy (and safety) of faricimab in their own patients to decide on the best treatment among the several now available for wet AMD and DME,” he said.

Study history

Faricimab met its primary endpoints for a variety of studies: TENAYA and LUCERNE and its extension study AVONELLE X, which assessed the long-term safety and efficacy of faricimab for the treatment of wet AMD. YOSEMITE and RHINE as well as the extension study RHONE X measured the safety and efficacy of faricimab for the treatment of DME.

Extension studies AVONELLE X and RHONE X are still underway to determine the long-term safety and efficacy of wet AMD and DME, respectively. RHONE X is expected to conclude in August of 2023, and AVONELLE X is expected to conclude in August of 2024.^2,3

The COMINO and BALATON trials are currently evaluating the safety and efficacy of faricimab in patients with macular edema secondary to central retinal vein occlusion (RVO) and branch RVO. The study is expected to conclude in fall of 2023.⁴

TENAYA and LUCERNE trials

The results of the phase III TENAYA and LUCERNE trials showed that faricimab met the primary efficacy endpoints of noninferiority to aflibercept (Eylea, Regeneron Pharmaceuticals) in the change in the best-corrected visual acuity (BCVA), durability, and safety for treating patients with neovascular age-related macular degeneration (AMD), according to Robyn Guymer, a professor of ophthalmology at Melbourne University and deputy director of the Centre for Eye Research Australia in Melbourne.

These 2 clinical trials are large identical randomized, double-masked, investigations that are evaluating the dual inhibition of angiopoietin-2 and vascular endothelial growth factor-A by faricimab.

Patients in these 112-week studies were treatment-naïve and randomized 1:1 to faricimab 6.0 mg up to every 16 weeks after 4 initial every-4-week doses or aflibercept 2.0 mg every 8 weeks after 3 initial every-4-week doses.

After the initial dosing and assessments of the disease activity, the patients receiving faricimab were treated at fixed intervals, ie, every 16 weeks, every 12 weeks, or every 8 weeks.

The patients treated with faricimab then followed a personalized treatment interval, that is, a protocol-driven treat-and-extend regimen with interval adjustment that was based on individualized treatment responses as assessed by the prespecified anatomic and functional criteria at study drug dosing visits up to week 108.

The primary efficacy endpoint was the change in the BCVA compared with baseline averaged over weeks 40, 44, and 48 and compared with aflibercept.

The secondary safety endpoints were the proportions of patients treated every 8, every 12, and every 16 weeks; the proportion of patients who had increases of 15 letters or more or who did not have losses of 15 letters or more; and the changes in the BCVA and central subfield thickness (CST) over time.

The safety endpoints were the incidence and severity and non-ocular adverse events.

YOSEMITE and RHINE trials

The 1-year results of the ongoing 2-year YOSEMITE and RHINE trials showed favorable results for faricimab for treating diabetic macular edema (DME). The visual gains achieved with every-16-week dosing were non-inferior to those of aflibercept (Eylea, Regeneron Pharmaceuticals) dosed every 8 weeks.

The anatomic gains also favored faricimab compared with aflibercept. Faricimab also demonstrated a good safety profile with very low rates of inflammation.

The YOSEMITE and RHINE trials, which are identical, randomly assigned double-masked studies compared the efficacy, durability, and safety of faricimab with aflibercept in patients with center-involving DME who were either treatment-naïve or received previous treatment with anti-VEGF therapy.

Patients were randomly assigned 1:1:1 to faricimab 6.0 mg every 8 weeks (Q8W) after 6 initial every-4-week Q4W doses; faricimab 6.0 mg treated according to a personalized treatment interval (PTI) based on the treat-and-extend concept after 4 initial very-4-week doses; or aflibercept 2.0 mg every 8 weeks after 5 initial every-4-week doses.

The primary efficacy endpoint was the mean change in the best-corrected visual acuity (BCVA) from baseline averaged over study weeks 48, 52, and 56. The secondary endpoints were the proportion of patients with a 2-step or more improvement in the Early Treatment Diabetic Retinopathy Diabetic Retinopathy Severity Scale (ETDRS-DRSS) from baseline, the proportion of patients with a 15 or greater gain in ETDRS letters from baseline, the change in central subfield thickness (CST) from baseline, and the proportion of patients in the PTI arm receiving doses every 4, every 8, every 12, or every 16 weeks at 1 year.

References

1. FDA accepts application for Roche’s faricimab for the treatment of neovascular age-related macular degeneration (NAMD) and diabetic macular edema (DME). Roche. https://www.roche.com/investors/updates/inv-update-2021-07-29b.htm

2. A study to evaluate the long-term safety and tolerability of Faricimab in participants with neovascular age-related macular degeneration. https://clinicaltrials.gov/ct2/show/NCT04777201

3. A study to evaluate the long-term safety and tolerability of Faricimab in participants with diabetic macular edema. https://clinicaltrials.gov/ct2/show/NCT04432831

4. A study to evaluate the efficacy and safety of Faricimab in participants with macular edema secondary to branch retinal

LAS VEGAS — For patients with diabetic macular edema, long-term response to vascular endothelial growth-factor (VEGF) inhibitors can be predicted after just three injections, according to a post hoc analysis of data from Protocol I of the Diabetic Retinopathy Clinical Research Network (DRCR.net).
  
Patients who did not respond to three monthly anti-VEGF injections were destined to remain relatively unresponsive at 3 years, said Pravin Dugel, MD, from the University of Southern California Keck School of Medicine in Los Angeles and Retinal Consultants of Arizona in Phoenix.
  
This is a group of patients who might benefit from treatments that have an alternate mode of action, he pointed out.
  
Dr Dugel presented results from the phase 3 Early Anti-VEGF Response and Long-term Efficacy (EARLY) study here at the American Academy of Ophthalmology 2015 Annual Meeting.
  
He and his colleagues evaluated 854 eyes from 691 patients with diabetic macular edema treated with ranibizumab according to an established protocol over a period of 3 years.
  
The team assessed study eyes for best corrected visual acuity after 3 months and throughout the study period. The results were striking; patients “tracked” according to their 12-week response.
  
In the group of patients who gained at least 10 letters after three injections, this strong response at 12 weeks was maintained during the 3-year study period. In the group of patients who gained five to nine letters, improvement was limited at 3 years. And in the group of patients who gained four letters or less, the benefit was minimal at 3 years, Dr Dugel reported.
  
“The point here is that three injections, after 12 weeks, can very confidently predict what’s going to happen to the patient — not just for 1 year, but for up to 3 years,” he told Medscape Medical News.
  
  
Change in Mean Best Corrected Visual Acuity Over Time
  
Mean Letters Gained 0 to 4 Letter Group (n = 135) 5 to 9 Letter Group (n = 79) ≥10 Letter Group (n = 126)
At 3 months 0.3 6.9 15.2
At 1 year 2.8 8.2 16.5
At 3 years 3.0 8.2 13.8
  
  
After multivariate adjustment, there was a significant correlation in best corrected visual acuity gain for all three groups of patients between week 12 and years 1 and 3 (P < .001).    "The number gaining less than five letters was around 39%," Dr Dugel reported. "Overall, these patients do well on anti-VEGF agents, but when you look at the outcomes with more granularity, you see that many don't. Right now, this is the only way to predict who will be in that group."    All anti-VEGF agents are relatively similar in efficacy in this disease. There's no evidence for switching, and no evidence that switching from one anti-VEGF agent to another is better. On the basis of these results, Dr Dugel said that clinicians might want to consider therapies with alternative modes of action for patients with diabetic macular edema who are inadequately responsive after three injections.    In fact, if a patient does not respond to an anti-VEGF agent after three injections, "consider alternative modes of therapy," he said.    But Dr Dugel said he would not switch to another anti-VEGF. "All anti-VEGF agents are relatively similar in efficacy in this disease. There's no evidence for switching, and no evidence that switching from one anti-VEGF agent to another is better," he explained.    A lack of response probably indicates a different disease mechanism at work, Dr Dugel reported.    Diabetic macular edema "may evolve from a condition that is primarily permeability-driven to one that is primarily inflammatory-driven, and in a new patient, you have no idea where they are on this spectrum. The patient may have thrown the multifactorial switch and may now be in the inflammatory phase as opposed to the early permeability phase of disease," he pointed out. "This is where steroids come in."    Dr Dugel said that the dexamethasone intravitreal implant (Ozurdex, Allergan) is the natural choice for the initial intervention. After that, there is fluocinolone acetonide (Iluvien, Alimera Sciences), which has also been approved by the US Food and Drug Administration.    This analysis of the EARLY data confirms what Ninel Gregori, MD, from the Bascom Palmer Eye Institute in Miami, has been doing for some time.    "By 3 months, I do think you know how a patient is going to do on anti-VEGF agents," she told Medscape Medical News. "This is how I have been managing patients already. What I do with my patients, in particular my diabetics, is to give 3 months of injections with bevacizumab, then evaluate. If they have improved, great, I continue the treatment. If they have not, I switch to a different anti-VEGF agent, usually aflibercept, and inject another three times. If there is still no change, I may go to a steroid next," she said.    Although this study was based on DRCR.net data, the analysis was not reviewed or approved by DRCR.net. Dr Dugel reports consulting for Allergan, Abbott Medical Optics, Acucela, Alcon Laboratories, Alimera Sciences, Digisight, Genentech, Novartis Pharmaceuticals, Ophthotech, Ora, Regeneron, and ThromboGenics. Dr Gregori has disclosed no relevant financial relationships.    American Academy of Ophthalmology (AAO) 2015 Annual Meeting. Presented November 14, 2015.    Source: Medscape

During a press conference led by retinal disease specialists and sponsored by Bayer Healthcare, experts announced the approval of the latest treatment for diabetic retinopathy in patients with diabetic macular edema (DME) in Egypt.
  
Dr Hany Hamza, Professor of Ophthalmology at Cairo University and Retinal Diseases Consultant said, “with nearly 21 million people worldwide suffering from DME, phase 3 of VIVID-DME and VISTA-DME clinical trials revealed that aflibercept offers diabetes patients suffering from impaired vision a new treatment option allowing them to proactively manage disease progression and achieve sustained improvement.”
  
Egypt now joins 30 other countries which have approved aflibercept which was authorized for DME treatment by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) in August 2014.
  
“Diabetic Macular Edema (DME) is a common complication of diabetes, causing damage to the retina, which may lead to poor vision and vision loss,” said Dr Hamza. “Visual impairment resulting from DME affects nearly 3% of diabetes patients worldwide, making DME a leading cause of vision loss in working-age adults.”
  
“In Egypt DME is a serious challenge; it affects nearly 30% of a total of 7.5 million people living with diabetes in the country. DME occurs when blood vessels in the retina are damaged by chronic high blood sugar levels caused by diabetes. This in turn can cause severe vision loss or blindness,” added Dr Hamza.
  
Dr Magdy Moussa, Professor of Ophthalmology at Tanta University and Retinal Diseases Consultant shed light on the results of Phase 3 of VIVID-DME and VISTA-DME clinical trials, “after one year of regular therapy, patients treated with aflibercept showed significant improvements gaining, on average, the ability to read approximately two additional lines on an eye chart. Moreover, 33% of patients regained the ability to read three additional lines after only eight injections.”
  
Aflibercept which is injected into the eye once a month, for an initial five months, then once every two months, minimizes the development of abnormal retinal vessels, by blocking the vascular endothelial growth factor (VEGF), one of the natural growth factors in the body which play a significant role in diabetic retinopathy incidence. By reducing the rate of development of new blood vessels, leakage is minimized or prevented.
  
“Aflibercept represents an effective and comprehensive treatment for DME; it is currently the only treatment option for diabetic retinopathy in patients with DME that is approved for bimonthly dosing after an initial monthly dosing period. Moreover, current treatments which block VEGF only inhibit the VEGF-A protein, whereas aflibercept inhibits all the different VEGF-A proteins, in addition to PlGF,” said De Moussa.
  
“People living with diabetes must closely monitor their blood sugar levels and go for eye checkups once every year,” said Dr Hamza. “Early detection achieves the best treatment outcomes – patients who discover the disease early are successful in controlling it and preventing loss of vision.”
  
Source: Albawaba

The non-profit Angiogenesis Foundation today launched a nationwide multimedia campaign EyeCanDoIt as their contribution to World Sight Day. The campaign addresses an important public health burden of diabetes and the need to prevent vision loss due to diabetic retinopathy and diabetic macular edema. The campaign’s message focuses on the impact of vision loss in terms of quality of life for people with diabetes, as well as the importance of good blood sugar control and having an annual dilated eye exam for vision screening to ensure early diagnosis and prompt treatment.
  
The non-profit Angiogenesis Foundation today launched EyeCanDoIt, a nationwide multimedia campaign as their contribution to World Sight Day. The campaign addresses the public health burden of and the need to prevent vision loss from diabetes, due to diabetic retinopathy and diabetic macula edema. The campaign message focuses on the impact of vision loss on quality of life for people with diabetes, the importance of good blood sugar control, and having a dilated eye exams annually for vision screening for ensure early diagnosis and prompt treatment.
  
Website: http://www.eyecandoit.org/
Facebook: https://www.facebook.com/eyecandoit
Twitter: https://twitter.com/EYE_candoit
  
The campaign’s website EyeCanDoIt.org is the first ever illustrated and audio-accompanied resource for people with diabetes and their caregivers, offering easy to understand explanations about the effects of diabetes on the eye, and the steps that can be taken to protect vision throughout their lives. EyeCanDoIt also explains cutting edge treatments that can halt and even reverse vision loss from diabetic retinopathy and diabetic macular edema.
  
“Until now, there has been very little information available for people with diabetes about how to prevent vision loss. EyeCanDoIt is comprehensive, easy-to-understand, and designed to empower those with diabetes to take an active role in getting their eyes screened, and to work with their health team to coordinate their care,” commented Dr. William Li, President and Medical Director of the Angiogenesis Foundation.
  
Key features of the EyeCanDoIt campaign are
  
– Educational content describing diabetes and the eye, how diabetic eye disease is diagnosed, and modern treatment options for diabetic retinopathy and diabetic macular edema;

– Storybook-style Illustrations and audio narration bringing the content to life;

– List of resources that offer guidance in managing diabetes and vision loss.
  
  
The Angiogenesis Foundation (www.angio.org) is a Cambridge, Massachusetts based nonprofit organization dedicated to improving global health through medicines, lifestyle, and dietary interventions based on angiogenesis, the process of new blood vessel growth.
  
To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/the-angiogenesis-foundation-launches-nationwide-campaign-for-saving-vision-on-world-sight-day-300156568.html

The U.S. Food and Drug Administration today expanded the approved use for Eylea (aflibercept) injection to treat diabetic retinopathy in patients with diabetic macular edema.
  

Diabetic retinopathy (DR) is the most common diabetic eye disease and is a leading cause of blindness in working adults in the United States.
  

“Diabetes is a serious public health crisis, affecting more patients every year,” said Edward Cox, M.D., M.P.H, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval gives patients with diabetic retinopathy and diabetic macular edema another therapy to treat this vision-impairing complication.”
  

In February, the FDA approved Lucentis (ranibizumab) injection 0.3 mg to treat DR in patients with DME.
  

Eylea is administered by a physician as an injection into the eye. It is intended to be used along with appropriate interventions to control blood sugar, blood pressure and cholesterol.
  

The safety and efficacy of Eylea to treat DR in patients with DME were evaluated in 679 participants in two clinical studies where participants were randomly assigned to receive Eylea or macular laser photocoagulation, a laser-based treatment used to burn small areas of the retina. At week 100, participants being treated with Eylea showed significant improvement in the severity of their DR, compared to patients who did not receive Eylea.
  

Aflibercept is an anti-VEGF drug that has also been FDA approved for wet age-related macular degeneration, diabetic macular edema, and macular edema following retinal vein occlusion– all vision-threatening conditions.
  

Source: FDA

Retinal venular calibre may predict visual outcome in diabetic macular edema patients given the anti-vascular endothelial growth factor (VEGF) monoclonal antibody ranibizumab, a pilot study suggests.
  
Factors predictive of the response to ranibizumab in this patient population are currently not known, but previous research indicates that retinal vascular calibre could be one such factor, say Quan Nguyen (University of Nebraska Medical Centre, Omaha, USA) and colleagues.
  
This study used data from individuals with diabetic macular edema who received intravitreal ranibizumab, either alone or together with laser treatment, in the phase II READ-2 trial.
  
Using optic disc-centred fundus photographs, the researchers calculated the baseline central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE), defined as the mean vessel calibre of the six largest arterioles and venules, respectively, in an area one-half to one-disc diameter from the optic disc margin.
  
And best-corrected visual acuity was assessed at baseline and a year after ranibizumab therapy using the Early Treatment of Diabetic Retinopathy Study chart.
  
Following treatment, 10 eyes from the same number of patients showed moderate improvement in vision, defined as a minimum two-line gain. These eyes had a significantly wider baseline CRVE than the 25 eyes from as many individuals whose vision did not improve moderately, at 248.3 µm versus 226.6 µm.
  
By contrast, baseline CRAE did not vary significantly between the participants whose visual acuity did and did not improve.
  
Nguyen et al propose that retinal specialists could use CRVE to predict visual improvement after intravitreal ranibizumab treatment in patients with diabetic macular edema.
  
Source: News Meical

The U.S. Food and Drug Administration today expanded the approved use for ranibizumab injection 0.3 mg (Lucentis) to treat diabetic retinopathy (DR) in patients with diabetic macular edema (DME).
  

Diabetic retinopathy is the most common diabetic eye disease and is a leading cause of blindness in adults in the United States. According to the Centers for Disease Control and Prevention, diabetes (type 1 and type 2) affects more than 29 million people in the United States and is the leading cause of new blindness among people ages 20 to 74 years. In 2008, 33 percent of adults with diabetes aged 40 years or older had some form of DR. In some cases of DR with DME, abnormal new blood vessels grow on the surface of the retina. Severe vision loss or blindness can occur if the new blood vessels break.
  

“Diabetes is a serious public health crisis, affecting more patients every year,” said Edward Cox, M.D., M.P.H, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval gives patients with diabetic retinopathy and diabetic macular edema the first significant therapy to treat this vision-impairing complication.”
  

The drug’s safety and efficacy to treat DR with DME were established in two clinical studies involving 759 participants who were treated and followed for three years. In the two studies, participants being treated with ranibizumab showed significant improvement in the severity of their DR at two years compared to patients who did not receive an injection.
  

The FDA granted ranibizumab (Lucentis) for DR with DME breakthrough therapy designation. The FDA can designate a drug a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may demonstrate a substantial improvement over available therapies for patients with serious or life-threatening conditions.
  

The FDA previously had approved ranibizumab (Lucentis) to treat DME and macular edema secondary to retinal vein occlusions, both of which cause fluid to leak into the macula resulting in blurred vision. Ranibizumab (Lucentis) also is approved to treat wet (neovascular) age-related macular degeneration (AMD), a condition in which abnormal blood vessels grow and leak fluid into the macula.
  

Source: FDA

Vision gains achieved at the conclusion of the RIDE/RISE studies were maintained in patients with diabetic macular edema who were enrolled in a 2-year open-label extension study, Michael S. Ip, MD, told colleagues at Retina 2015. Improvements in retinopathy level were also sustained.
  

After 3 years in RIDE/RISE, 500 participants entered an open-label extension in which ranibizumab 0.5 mg (Lucentis) was given as needed in all three treatment arms according to re-treatment criteria. Mean follow-up time was 14.1 months, less than the anticipated 24 months due to the approval of ranibizumab for DME.
  

One “pitfall” in the analysis is that diabetic retinopathy severity was not a criterion for re-treatment, Ip said.
  

“With respect to visual acuity, it’s well known that we’re paying the price by waiting [to treat],” Ip said. In RIDE/RISE, patients with DME were randomized to one group of sham treatment or to one of two ranibizumab groups for the first 24 months.
  

“The group that was treated with sham for 2 years didn’t quite catch up to the groups that were treated initially with ranibizumab, and this remained the case throughout the open-label with PRN follow-on,” Ip said. “Another way to look at this is, with respect to visual acuity, all three groups in the open-label extension maintained their vision with PRN follow-on. They didn’t lose vision.”
  

Furthermore, fewer injections were given later in the study, with an annualized mean of only 3.8 injections in the extension study.
  

“Many of the injections were up front, in years 1, 2 and 3, and number of injections decreased in subsequent years,” Ip said.
  

Regarding diabetic retinopathy severity, levels were maintained from month 24 to month 36, and then to the end of the extension study.
  

“The two ranibizumab groups had a much higher proportion of patients with a 2- or 3-step or more regression in diabetic retinopathy level. This remained the case to the end of the open-label extension, despite PRN therapy and a mean of 3.8 annualized injections,” Ip said.
  

Ocular and systemic events differed little between the extension period and the end of the RIDE/RISE studies.
  

Source: Healio

Novel pharmacotherapies are in development for the treatment of diabetic macular edema.
  

We hope the combination of the current drugs as well as drugs in the pipeline … will help us to manage our patients with diabetic macular edema,” Quan Dong Nguyen, MD, said at Macula 2015.
  

Among promising pipeline drugs are ALG-1001, AKB-9778 and ASP-8232, he said, all targeting different pathways for treatment.
  

ALG-1001 is a small integrin peptide whose potency relies on anti-angiogenesis and vitreolysis to induce posterior vitreous detachment as well as vitreous liquefaction, according to Nguyen.
  

In a recently completed study combining ranibizumab (Lucentis) with ALG-1001 to treat choroidal neovascularization, the combined therapy reduced the area of neovascularization better than standalone therapy, he said.
  

A phase 2 study of ALG-1001 for treatment of DME is underway.
  

Another pipeline drug under study for treatment of DME, AKB-9778, is a small molecule that targets the enzyme that deactivates the Tie-2 gene. In its normal state, Tie-2 maintains the blood-retinal barrier in normal vasculature. AKB-9778 is administered via subcutaneous injection and is rapidly absorbed and rapidly eliminated.
  

In a phase 1 study of the molecule comparing four different doses given twice daily for 28 days, best corrected visual acuity improved by at least six letters in the three higher doses: 15 mg, 22.5 mg and 30 mg. As well, the study showed good correlation of visual acuity gain and anatomic improvement, he said.
  

“The Tie-2 pathway is critical in the initiation and propagation of diabetic eye disease,” Nguyen said. “AKB-9778, a small molecule activator of Tie-2, has shown promising results in early studies of diabetic eye disease.”
  

The TIME-2 study involving 144 patients randomized to study drug plus ranibizumab, study drug plus sham, or placebo is underway to evaluate the effect of AKB-9778 used in combination with the anti-VEGF.
  

A third promising molecule, ASP-8232, is a VAP-1 inhibitor that has been shown in animal models to improve the ability to reduce ocular hyperpermeability when used in combination with anti-VEGF, according to Nguyen.
  

Source: Healio

Vitrectomized eyes fared as well as non-vitrectomized eyes after treatment with ranibizumab for diabetic macular edema, according to a study presented at Macula 2015.
  

“The efficacy of ranibizumab in the treatment of diabetic retinopathy is well established, but there remain some uncertainties in clinical management with ranibizumab for DME,” Jack Wells, MD, said. “There’s a common clinical impression that the duration of action of anti-VEGF injected in eyes with prior vitrectomy would be shorter than in eyes without prior vitrectomy due to more rapid clearing of the drug, and therefore the treatment would be less effective.”
  

To investigate that theory, Wells and colleagues at the Diabetic Retinopathy Clinical Research Network used 3-year data from the DRCR.net Protocol I to analyze eyes with and without vitrectomy before enrollment assigned to intravitreal ranibizumab (Lucentis) with prompt or deferred laser.
  

“In this small group of eyes with vitrectomy prior to enrollment, the change in vision and OCT [central subfield thickness and volume] from baseline and the number of injections and lasers were fairly similar in eyes with and without prior vitrectomy, after you adjust for baseline imbalances,” he said.
  

Baseline differences in ocular characteristics of vitrectomized eyes included worse visual acuity and thinner maculas, as well as a greater likelihood to have undergone cataract surgery and previous treatment for DME. Non-vitrectomized eyes had milder diabetic severity scores, and vitrectomized eyes had greater tendency for proliferative disease.
  

“There was less rapid improvement in macular edema in vitrectomized eyes, but overall at the end of the 3 years, there were really no differences,” Wells said.
  

Source: Healio