, Theodore Leng, MD, Department of Ophthalmology, Stanford University, discussed his presentation on the natural history disease progression among adults with 

dry age-related macular degeneration (AMD)

His talk entitled "A Real-World Study of Prevalence and Natural History Disease Progression Among Adults With Dry AMD in the IRIS® Registry," was presented at the 

American Academy of Ophthalmology 2021 Meeting

Leng highlighted the benefit of the IRIS registry in this investigation, with longitudinal data from over 70 million unique patients and 412 million patient visits in the registry, encompassing 70 - 75% of all ophthalmology and retina visits in the United States.

"We wanted to see what the patient journey was for dry AMD patients when they showed up as a mild or intermediate, dry AMD patient,” he said. “Did they progress to advance disease with geographic atrophy or neovascular AMD and how long did that take?”

Then, Leng discussed the findings of the data set, analyzing 645,000 dry AMD patients where 90% of patients had mild to intermediate dry AMD. He noted this data shows that a large proportion of patients with AMD have early stages, which is not a main focus of current therapeutic treatments.

“I think the other major findings are that the probability of maintaining a dry AMD stage, so if you started out as a mild dry or intermediate dry, the probability of staying in that stage on an annual basis was about 80 to 90%, across all the disease stages,” he said.

However, Leng noted that the conversion from mild to intermediate, the rate was over 3 times higher for patients who are intermediate to an advanced stage. At a rate of per 100 person-years of progression to geographic atrophy, data show it was 3 times higher among those with intermediate dry AMD compared to mild dry AMD.

Then, he discussed the visual acuity component of the study, explaining that visual acuity was shown to get worse faster if you had a more progressive stage of dry AMD.

“If you had geographic atrophy, those patients progress, as far as vision is concerned, more rapidly than those with mild, dry AMD,'' Leng said. “And dry AMD progression to geographic atrophy and wet AMD were also faster once you reach the intermediate dry AMD stage.”

As a result, Leng noted that one of the key takeaways that he took from the study included a specific focus on intermediate AMD, as an area of huge unmet need.

“I think addressing the intermediate AMD population is going to be a key target next for us as a specialty, to really develop therapies that can prevent progression or stop progression, maybe even reverse disease in that population, because this study has shown that those intermediate AMD patients are at the highest risk of progressing to worse vision states, as well as more advanced disease states in AMD,” Leng said.

Additionally, Leng spoke on the impact of port delivery systems (PDS) on the future of care and how it will reduce both the treatment burden of patients with monthly injection visits. He also noted it may aid retinal physicians in addressing vision threatening diseases, particularly as the population ages and the bandwidth of clinicians is stretched thin.

“I think having a sustained delivery device, like the port delivery system, is really going to help kind of unload our schedules a little bit so we can care for patients, with other indications and also new therapies that are coming to market,” Leng said.

When looking forward, Leng once more pointed to better characterizing intermediate AMD and narrowing the definition from mild AMD to geographic atrophy by determining those in-between stages.

“I think better characterizing this population will then lead to better studies, both for natural history and for potential therapeutics that are hopefully being worked on by our industry partners,” he said.

Videos

Dr. Leng discusses the progression of dry AMD patients in the IRIS registry from early stages to potential GA, as well as the benefit in narrowing the clinical definition of intermediate dry AMD. 

Theodore Leng, MD: Characterizing the Definition, Rates of Intermediate Dry AMD

A combination of an optogenetics device and gene therapy has shown to be safe, tolerable and efficacious in the treatment of end-stage blindness in patients with 

, José-Alain Sahel, MD, Distinguished Professor and Chairman, Department of Ophthalmology, University of Pittsburgh School of Medicine, discussed both the safety and efficacy that was observed, as well as the implications of the findings of the PIONEER trial. 

Sahel described the PIONEER trial as the first in-human optogenetic trial combining gene therapy to deliver proteins which are photosensitive to remaining cells in the retina, in combination with a medical device that projects light into the eye to activate the proteins. 

"The third step is rehabilitation of a patient to learn how to adjust for goggles and how to understand the type of vision that is being formed, Sahel said. "So, it's a combination of three technologies."

Sahel noted the vector was well tolerated, with no significant safety signal besides inflammation, which he attributed to the gene therapy. However, nothing was considered damaging or detrimental to the retina. 

Additionally, he informed on the 9 patients who have been treated so far, with the Data and Safety Monitoring Board (DSMB) approving the extension of the highest dose of the gene therapy to more patients. 

"The other part is the efficacy we had published a few months ago on the first ever patient that's got vision restoration using this approach," he said. "And I was able to report at the meeting on the second patient was treated more recently, but as also demonstrated visual benefit."

Sahel discussed the future of the study, noting that more patients are being brought back who left the study due to the COVID-19 pandemic, as well as improving the stimulation goggles. 

"We are working on exploring more patients at the highest dose to see what level of vision will be obtained," he said. 

"Optogenetics in the Clinic: Safety and Efficacy Updates on the Phase I/II Clinical Trial PIONEER," was presented at 

At AAO 2021, Dr. Sahel discussed the findings of the PIONEER trial on the combination of an optogenetics device and gene therapy in treatment of RP.  

José-Alain Sahel, MD: Safety, Efficacy of Optogenetic Treatment for Retinitis Pigmentosa

New data delivered today from global pharmaceutical company UCB and in late October at the 2021 Fall Clinical Dermatology showcased the versatility of bimekizumab, an investigational humanized IgG1 monoclonal antibody designed to inhibit both interleukin (IL)-17A and IL-17F cytokines responsible for driving inflammatory processes.

Promising results in the treatments of both 

 were detailed in the recent announcements.

 exploratory trial data, indicated rapid, deep clinical responses in patients with moderate-to-severe plaque psoriasis.

Though not yet approved in the United States, data on bimekizumab remains positive, as alluded to in recent research.

Today, global pharmaceutical company UCB announced positive top-line interim analysis results from phase 3 of the BE OPTIMAL study, which assessed the efficacy and safety of bimekizumab in adults with active psoriatic arthritis who disease-modifying anti-rheumatic drug naïve.

The company announced that the study had met its primary endpoint and ranked secondary endpoints with statistical significance.

Patients treated with the biologic in the study achieved 50% or greater improvement in signs and symptoms of disease from baseline, compared with placebo at week 16 of the study, according to measurements made by the American College of Rheumatology (ACR) 50 response.

Additionally, among ranked secondary endpoints, patients treated with bimekizumab demonstrated significant improvements in physical function at week 16 of the study, as measured by the Health Assessment Questionnaire-Disability Index.

Data were presented at the 2021 Fall Clinical Dermatology Conference that occurred from October 21-24 suggested that the biologic demonstrated the lowest number needed to treat (NNT) for Psoriasis Area and Severity Index (PASI) 90 and PASI 100 skin clearance levels compared with other biologics during a 16-week study of patients with moderate-to-severe plaque psoriasis.

The NNT analysis was born out a lack of head-to-head studies that directly compared all available treatments for plaque psoriasis.

A large, systematic literature review preceded the current analysis and featured 86 randomized controlled trials. The data was presented at the International Society of Pharmacoeconomics and Outcomes Research (ISPOR).

In an interview with HCPLive, Jeffrey Stark, MD, Head of Immunology at UCB, spoke of the promise of bimekizumab for the treatment of psoriasis compared to other biologics such as ixekizumab, secukinumab, and adalimumab.

In the current analysis, Stark noted that the “spectrum of available mechanism of action” were represented.

Regarding NNT, which refers to the number of individuals that need to be treated with a given therapy in order to achieve specific outcomes, bimekizumab showed the most promise.

“We’re very happy to see in the results of the number needed to treat analysis that across this spectrum level biologic therapies bimekizumab had the lowest number needed to treat for both PASI 90 and for PASI 100,” Stark said. “So, those numbers for PASI 90, for example, were 1.22 for bimekizumab and for PASI 100 were 1.74.”

Stark further contextualized the data, saying that only 1.22 patients would need to be treated with the biologic for 1 patient to achieve PASI 90, and only 1.74 or fewer needed to be treated for 1 patient to achieve complete and total clearance.

“So, these are quite remarkable numbers, we feel and certainly reflect very favorably on the effectiveness of bimekizumab in comparison to the other available therapies that plaque psoriasis patients had at their disposal today,” Stark said.

To hear more on the promise of bimekizumab therapy for plaque psoriasis patients, watch the interview above.

The biologic has shown promise in the management of both plaque psoriasis and psoriatic arthritis.





New Data Shows Versatility and Promise of Bimekizumab Therapy

Titilope Fasipe, MD, PhD, Assistant Professor of Pediatric Hematology-Oncology, Baylor College of Medicine, was invited to be the opening plenary speaker at the National Organization for Rare Disease (NORD) summit.

®, Fasipe discussed her experience as a speaker and as a health care provider at the summit. In her plenary presentation, she shared her personal experience as a patient with 

"What you have at the summit is a true bringing together of expert minds," Fasipe said. "The things that I feel the most energized about are when I see the national leaders coming forth and standing by rare disease."

Fasipe saw Dr. Francis Collins from the National Institutes of Health (NIH) in attendance, as well as leaders from the Center of Disease Control and the US Food and Drug Administration.

When she saw the national leaders teaching at the summit, and being candid about what it takes to help treat various diseases, it had a meaningful impact. 

There was a session that educated organizations on smart health policy procedures. According to Fasipe, those are tools that all providers could use. The legislative system isn't exactly intuitive so gaining a better understanding of it is beneficial.

She explained that NORD has been very supportive of diversity initiatives. The summit served as a sort of training ground, according to Fasipe, that addresses the obstacles that come with treating or advocating for any rare disease. 

Dr. Fasipe shares about her experience at the National Organization for Rare Disease Summit 2021 as the opening plenary speaker. 

Titilope Fasipe, MD, PhD: Advocacy for Rare Disease at the NORD Summit

, Robert L. Avery, MD, CEO, California Retina Consultants, highlighted the data he presented at the 

 on the REGENXBIO study of RGX-314, a gene therapy for 

The product is a monoclonal antibody similar to ranibizumab, injected subretinal. The major study is the Phase 1/2a study for the treatment of these conditions, where the gene therapy RGX-314 treated the macular degeneration as though it was an injection.

Within the study, a total of 42 patients were enrolled, with 5 ascending dose escalation cohorts. In the first 2 cohorts, no benefit was seen with a lower dose.

However, Avery noted that in cohort 3, 4, and 5, they saw a definite effect on patients who had been anti-VEGF dependent, or frequent fliers, as Avery called them. They had on average 9 or more injections per year, potentially for numerous years.

“They were heavily treated patients, it was a dramatic reduction in their need for therapy, while maintaining good vision, stable vision and good thickness results,” he said.

The study did show 20 severe adverse events in 13 patients that were felt to not have been related to the drug treatment, aside from a single event that was pigmentary changes in the macula of one patient.

Avery went on to note that 69% of the patients develop pigmentary changes in the retina, mostly in the far interior periphery. However, they were considered mild, except if there was an effect on visual acuity. He explained that these patients were not treatment naive and had a history of atrophy before enrollment.

“Other than that the drug was really well tolerated, Avery said. “There were no signs of significant inflammation as opposed to many other gene therapies. There was no prophylactic steroid treatment given for this trial, just the typical drops we would do after vitrectomy and tapered off, but really no significant inflammation, which is, I think, a very important point with this study.”

Further studies include ATMOSPHERE and a second unnamed study which begin enrolling in the 4th quarter of 2021, with about 300 patients. They are randomized to 2 doses of RGX-314, or ranibizumab.

“Two Year Results from the Subretinal RGX-314 Gene Therapy Phase 1/2a Study for the Treatment of nAMD, and an Update on Suprachoroidal Trials,” was presented at 

Dr. Avery discusses the positive results of RGX-314 gene therapy, noting dramatic reduction in need for therapy, with stable vision and good thickness results

Robert L. Avery, MD Highlights Results on RGX-314 For the Treatment Of Wet AMD 

Investigators might just be scratching the surface of the potential for bentracimab, a novel, recombinant, human monoclonal antibody antigen-binding fragment being studied as a potential treatment to reverse the antiplatelet effects of ticagrelor in patients who present with urgent surgery or an invasive procedure or experiencing uncontrolled major or 

annual meeting as a late-breaking poster.

, Deepak L. Bhatt, M.D., M.P.H., Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital and professor at Harvard Medical School, explained the promise and utility behind bentracimab and what happens next in the REVERSE-IT study.

“Potentially, if this is approved, it would really be convenient to have an agent that would reverse ticagrelor’s effect,” Bhatt said. “And use of ticagrelor is likely going to grow, there’s a number of recent indications for use of ticagrelor.”

Some of the indications for the blood thinner include for patients with high risk coronary artery disease with or without diabetes, prior myocardial infarction, high-risk coronary artery disease, transient ischemic attack, and stroke.

However, like all antiplatelet drugs, bleeding is considered a risk for ticagrelor.

“Assuming the regulator agencies approve it, for a patient that is on potentially long-term ticagrelor and has a bleeding episode, now we’ve got an agent that can at least reverse that component of bleeding.

Bentracimab achieved the predetermined primary endpoint of immediate and sustained reversal of the antiplatelet effects of ticagrelor in the REVERSE-IT trial.

Deepak Bhatt, MD, MPH: The Potential of Bentracimab

According to new phase 3 data presented at the 

, brolucizumab was noninferior to aflibercept in the treatment of 

center-involving diabetic macular edema (DME)

During an interview with HCPLive, Dilsher Dhoot, MD, California Retina Consultants, discussed his presentation on the outcomes of the KESTREL and KITE studies. In terms of fluid outcomes, data show that brolucizumab may have dried the retina better, compared to aflibercept, over the 52 week study period.

“There are key time points at 32 weeks and 52 weeks where we can actually do a head to head comparison in terms of resolution of subretinal, fluid, internal fluid, or compare if there's any fluid at all,” Dhoot said. “And we saw that, at these time points, brolucizumab had a greater proportion of patients that are fluid free.”

He noted that the still unmet need of durability in DME treatment, with patients in the current study actually observed to need less frequent injections. The median number of injections over the 52 week period was 7 injections for brolucizumab compared to 9 injections for aflibercept, with both agents having similar visual acuity outcomes.

“We also saw that just over 50% of patients were able to be maintained on a quarterly dosing,” Dhoot explained. “That's also something that makes treatment more palatable for patients, especially when they have a tough time getting in.”

Additionally, Dhoot spoke on the safety profile in the study, which was generally similar, aside from some adverse events he noted were of “special interest.” In the KESTREL trial, there was a higher rate of intraocular inflammation in the 3 milligram dose, compared to the 6 mg dose, as well as cases of retinal vasculitis and occlusion.

“Interestingly, the KITE trial had similar rates of IOI, comparing brolucizumab and aflibercept, but there were no cases of retinal vasculitis,” he said. “There was a single patient that had a vascular occlusion in each group and these exclusions were not really related to inflammation.

The study will continue into a second year, with results from the 2-year data expected in 2022.

“I think that in general, as retina specialists, it is great to have another agent in our toolkit,” Dhoot said. “Having these results be positive in terms of efficacy and potentially increasing the durability and reducing fluid in these patients is a very positive thing overall."

“Brolucizumab For Treatment of Diabetic Macular Edema (DME): 52-Week Results from the KESTREL and KITE Phase 3 Studies,” was presented online at 

Dr. Dhoot discusses data on visual acuity from the phase 3 KESTREL and KITE trials, comparing brolucizumab to aflibercept at 52 weeks. 

Dilsher S. Dhoot, MD: Efficacy of Brolucizumab in Treatment of Diabetic Macular Edema 

rial) show bentracimab resulted in the reversal of the antiplatelet effects of ticagrelor in patients who present with urgent surgery or an invasive procedure or experiencing uncontrolled major or life-threatening 

The results from the 150 patient phase 3 trial were announced during the 

2021 American Heart Association (AHA) Scientific Sessions

Bentracimab achieved the predetermined primary endpoint of immediate and sustained reversal of the antiplatelet effects of ticagrelor. There was a 135% reduction in platelet inhibition (

<0.001) observed within 5-10 minutes following bentracimab infusion. This reduction sustained throughout all timepoints over 24 hours.

In addition, more than 90% of participants achieved the co-primary endpoint of good or excellent hemostasis within 24 hours of initiation of bentracimab therapy (

For safety, 5.3% of patients reported thrombotic events, none of which resulted in death or were considered to be related to the treatment. The drug was well-tolerated, with 5 non-serious adverse events reported by 3 patients, the most common of which were pain associated with surgical procedures.

, Deepak L. Bhatt, M.D., M.P.H., Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital and professor at Harvard Medical School, explained how promising the initial results actually are.

There was a 135% reduction in platelet inhibition observed within 5-10 minutes following bentracimab infusion.

Deepak Bhatt, MD, MPH: Promising Data From the REVERSE-IT Trial

Adverse events following treatment with brolucizumab of patients with 

neovascular age-related macular degeneration

 and persistent retinal fluid led to the discontinuation of the Phase 3a MERLIN trial, according to new data presented at the 

In an interview with HCPLive, presenting author, Arshad Khanani, MD, Managing Partner, Sierra Eye Associates, discussed the study meeting the primary endpoint of noninferiority of brolucizumab to aflibercept.

He noted that there was superiority of brolucizumab when looking at change from baseline to week 52, as well as patients who had more dry retina when treated with the agent. However, due to adverse events, it is not recommended to use brolucizumab more often than every 8 or 12 weeks following the loading dose.

“More ocular events of special interest the rate of inflammation in patients treated with Brolucizumab was 9.3%, compared to 4.5% in aflibercept,” Khanani said. “And that's why the second year of the MERLIN trial was discontinued.”

Khanani spoke on the expectation of the adverse events, explaining the prior knowledge of higher rates of intraocular events in brolucizumab treatment, compared to aflibercept. However, in the Phase 3 HAWK and HARRIER studies, the rate was 4%, compared to 9.3% in MERLIN.

“I think it has to do with the intensity and frequency of treatments,” he said. “In HAWK and HARRIER, patients received three monthly dosing and then Q8 and Q12 weeks. In this trial, we have patients who are treated with anti VEGF, and they're getting monthly continuous treatment of Brolucizumab.”

He then noted the goal of the study was to allow patients to control disease activity and stabilize anatomy so vision is not lost over time, as patients with persistent fluid, particularly intraretinal fluid, will lose vision over time.

“Keep in mind that this study was designed before we knew about the safety signals,” he said. “We knew about IOI rates, but there's also retinal vasculitis, retinal artery occlusion, those are the concerning events. We learned about that once Brolucizumab launched.”

Khanani spoke on data presented earlier this year about fluid in patients with a port delivery system, which showed the majority had no fluid and were well controlled. However, he noted that this is a different population of patients who have persistent fluid, despite receiving anti-VEGF injections.

“I think the port delivery system is really exciting to decrease the treatment burden for our patients as well as maintain anatomy,” Khanani said. “But, the question is, is this the right population where you have suboptimal responders to ranibizumab or aflibercept?

As a conclusion, Khanani summed up that brolucizumab cannot be given monthly and it is not for patients with persistent disease activity with vision loss.

“It is not for patients who are well controlled with current agents and and and the reason is the differences in safety,” he said. “Of course, anatomy is important, visual acuity is important, but if there's a safety concern or a signal that's different than obviously, we are going to use that as the last resort for our patients.”

Dr. Khanani highlights data from MERLIN showing noninferiority of brolucizumab to aflibercept in nAMD treatment, but a higher rate of intraocular inflammation.  

Arshad Khanani, MD Discusses Adverse Ocular Events After Brolucizumab Treatment 

Veeral Sheth, MD, Director of Clinical Trials, University Retina, discussed the late breaking findings of the phase 2b ALTISSIMO trial data from the 

The data from the trial found the mean durability in 1 milligram GB-102 group was 12 months, in patients with 

wet age-related macular degeneration (wet AMD)

. Sheth noted the results of this data showed really good durability of the agent.

“We saw 55% of the patients in the one milligram group did not need rescue therapy in that last six months part of the observation, so they went 12 full months without needing any rescue therapy,” he said.

He continued with mentioning the 4 adverse events of iritis in the 1 milligram group, which were treated successfully with topical steroids. Sheth noted that anything that can be done to extend the life of a drug is valuable, balanced out with both efficacy and safety.

“Obviously, the nice thing about GB-102 Is it can be delivered via intravitreal injection,” he said. “So, it's easy to do in the clinic and monitor those patients as well.”

Sheth mentioned the recent FDA approval of port delivery systems, which can help to extend the life of a drug in a patient’s eye, leading to fewer injections and improved quality of life. He concluded with his excitement on the future of ophthalmology, noting it is an “exciting time to be in ophthalmology.”

“It's really exciting times that we have different mechanisms of actions that we're exploring different ways of extending dosing intervals,” Sheth said.

“Intravitreal Sunitinib Malate Depot (GB-102): Durability and Safety in Wet Age-Related Macular Degeneration (ALTISSIMO, Phase 2B),” was presented at 

Dr. Sheth discusses the data from the late-breaking Phase 2B ALTISSIMO study. 