본 보고서는 수포성 각막병증(수포성 각막병증)에 대해 상세하게 분석했으며, 과거 역학 및 예측, 미국, EU 4개국(독일, 프랑스, 이탈리아, 스페인), 영국, 일본의 수포성 각막병증 시장 동향에 대해 조사 분석하였습니다.
이 보고서는 현재 치료법, 신약, 개별 치료법별 시장 점유율, 2020년에서 2034년까지 주요 7개국의 수포성 각화증 시장 규모 현황 및 예측을 제공합니다. 또한, 수포성 각화증 치료 시장 관행/알고리즘, 미충족 의료 수요를 다루며, 최적의 치료 기회를 발굴하고 시장 잠재력을 평가합니다.
각막증이라는 용어는 각막을 뜻하는 Kera와 병을 뜻하는 pathy라는 어원에서 유래되었습니다. 각막병증은 안질환 또는 전신질환에 의해 발병합니다. 각막병증에는 수포성 각막병증을 포함한 여러 가지 유형이 있습니다. 수포성 각막병증은 내피 기능 장애로 인해 각막에 작은 물집이나 수포가 형성되는 병적 상태입니다. 먼저 내피의 외상이 있고, 그 다음 간질과 상피의 부종이 진행됩니다. 상피의 부종은 수포의 형성을 초래하며, 이것이 수포성 각막병증이라는 이름의 유래입니다.
수포성 각막병증은 백내장 수술을 받고 인공수정체를 삽입한 사람에게 특히 많이 발생하기 때문에 가성 수포성 각막병증(PBK) 또는 가성 수포성 각막부종(PCE)이라고도 불립니다. 주요 특징은 각막에 액체를 함유한 물집이나 물집이 형성되어 통증, 흐린 시야 및 기타 시각 장애를 유발할 수 있다는 것입니다. 이 증상은 보통 각막의 투명성을 유지하고 체액 균형을 조절하는 세포의 가장 안쪽 층인 각막 내피의 손상으로 인해 발생합니다.
수포성 각막병증의 진단을 위해서는 일반적으로 시력검사, 세극등 검사, 각막의 두께와 투명도 평가 등의 종합적인 안과적 검사가 시행됩니다. 경우에 따라서는 각막의 손상 정도와 심각성을 평가하기 위해 각막 토포그래피나 경면 현미경 검사 등의 추가 검사가 필요할 수 있습니다.
수포성 각막염의 치료법은 근본적인 원인과 중증도에 따라 다릅니다. 초기에는 통증을 완화하고 각막을 보호하기 위해 윤활 점안제, 고삼투압제, 항녹내장제, 스테로이드, 연고, 붕대 콘택트렌즈 등 증상을 조절하는 보존적 수단을 사용합니다. 일본에서 승인된 동종세포치료가 효과적임이 입증될 수 있습니다. 그러나 병이 진행되어 시력이나 삶의 질에 큰 영향을 미치는 경우에는 수술적 치료가 필요합니다.
각막이식술, 특히 데스메탈 박리 자동내피각막이식술(DSAEK)이나 데스메탈 내피각막이식술(DMEK)과 같은 내피각막이식술(EK)은 수포성 각막병증에 대한 일반적인 수술적 치료법입니다. 이 수술은 손상된 각막 내피를 건강한 기증자 조직으로 대체하여 각막의 투명성을 회복하고 시기능을 개선합니다.
수포성 각막병증 치료제
Aurion Biotechnologies가 개발한 VYZNOVA는 일본에서 각막 수포증에 적응증을 가진 세포치료제로, '네르테펜도셀'이라는 동종 인간 각막 내피세포와 Rho 관련 코일코일 함유 단백질 키나아제를 억제하는 저분자 약물인 Y- 27632로 구성되어 있습니다. 27632로 구성되어 있습니다. 이 조합은 체외에서 완전히 분화된 각막내피세포(CEC)의 재생을 용이하게 합니다. 기증자의 각막 세포는 독자적인 다단계 공정을 거쳐 기성품 동종 CEC가 만들어집니다. 이 세포들은 안구에 주입되어 건강한 단층막을 형성하고 과도한 액체를 제거하여 각막 부종을 감소시킵니다.
2023년 3월 일본 의약품의료기기종합기구(PMDA)는 각막수포증 치료제로 VYZNOVA를 승인했습니다.
수포성 각막병증 신약
TTHX1114(NM141)은 섬유아세포 성장인자-1 단백질(FGF-1)의 유전자 재조합형입니다. 원래 FGF-1은 세포 증식 및 이동의 강력한 자극 인자이며, 세포 보호 작용을 가지고 있습니다. 이 화합물은 FGF 수용체의 7가지 형태 모두를 독자적으로 활성화시켜 그 효능의 한 요인이 되고 있습니다. 그러나 자연적으로 존재하는 FGF-1 분자는 반감기가 매우 짧습니다. 인공 FGF-1인 TTHX1114는 FGF-1 분자의 반감기를 연장하여 각막 내피세포의 증식과 이동을 자극하도록 설계되었습니다.
TTHX1114는 가성수포성각막증 등 각막내피질환 환자의 시력 회복을 목적으로 개발되었으며, 아주 가는 바늘을 이용해 소량의 TTHX1114를 전안부(각막 바로 뒤쪽)에 주입하는 안구 내 주사제로 개발되었습니다.
2023년 4월, 트레포일 테라퓨틱스는 백내장 수술과 함께 데스메막박리술(DSO)을 받는 후크스 내피각막이상증(FECD) 환자를 대상으로 한 TTHX1114의 임상 2상 결과를 ARVO(Association for Research in Vision and Ophthalmology) 연례 학술대회에서 발표했습니다.
EO2002는 독자적인 자성 세포 전달(MCD) 나노입자 플랫폼을 통해 개발된 질병을 조절할 수 있는 최초의 비수술적 자성 세포 기반 치료법으로, 자성 나노입자를 활용하여 세포 치료제를 적절한 표적 조직에 효과적으로 국소화, 유지 및 통합할 수 있도록 합니다. 효과적으로 국소화하고 통합하여 세포치료제의 전달, 유지 및 통합을 용이하게 합니다.
2024년 4월, 엠멕셀은 각막부종에 대한 EO2002의 안전성과 유효성을 평가하기 위한 미국 무작위 이중마스크 다기관 임상 1상 시험에서 마지막 환자에게 최종 투여를 완료했습니다. 탑라인 결과는 2024년 하반기에 발표될 예정이며, 임상 3상 피벗얼 시험은 2025년 1분기로 예정되어 있습니다.
현재 수포성 각막병증 치료 시장에는 약리요법과 수술요법이 모두 존재합니다. 세포치료, 생리식염수 점안이나 연고(염화나트륨 5%), 항생제, 항염증제, 항녹내장제, 윤활점안제 등의 약물요법이 증상 완화를 위해 사용됩니다. 그러나 내과적 치료가 좋은 것은 질병의 초기 단계에서만 가능하며, 실패한 경우에는 수술을 고려하게 됩니다.
각막 이식은 여전히 수포성 각막병증 치료의 표준으로, 손상된 내피를 기증자의 건강한 내피로 대체하여 내피세포의 정상적인 구조와 기능을 회복시키기 위해 손상된 내피를 기증자의 건강한 내피로 대체해야 하지만, 시력 회복에는 시간이 걸립니다. 이식편의 크기는 난시나 이차성 녹내장 등 이식편의 크기에 따른 합병증을 피하기 위해 보통 7-7.5mm입니다.
친수성 콘택트렌즈는 상피 수포에 수반되는 통증을 줄이기 위해 널리 사용되지만 부종의 양을 줄일 수는 없습니다. 콘택트렌즈는 5% 생리식염수와 함께 사용하면 상피 및 간질의 부종을 감소시키고 시력을 개선할 수 있습니다. 일반적으로 PBK에 수반되는 통증은 각막 신경 종말의 노출을 동반한 수포의 파열 또는 신경 종말의 스트레칭으로 이어지는 상피의 부종에 기인하며, 렌즈가 효과적인 각막 전 보호막 역할을 함으로써 렌즈가 제자리에 있는 한 통증이 완화될 수 있습니다.
세계 최초의 동종 세포 치료제의 승인은 각막 내피 질환 치료에 큰 진전을 가져왔으며, 2023년 3월 PMDA는 VYZNOVA를 각막 수포성 각막병증 치료제로 승인했습니다. 이 치료법은 비수술적 개입의 필요성을 해결하고, 한 명의 기증자로부터 완전히 분화된 CEC로 100개 이상의 눈을 치료함으로써 기증자 각막 부족을 극복합니다. 기증자 각막에서 채취한 건강한 세포는 특허 받은 새로운 다단계의 독자적인 특허 공정을 통해 배양되어 동종 완전분화 CEC를 생산합니다. 또한, 내피세포는 각막 내로 투여되어 건강한 단층으로 세포가 재증식하는 과정을 거칩니다. 각막에서 체액을 제거하여 각막 부종을 감소시킬 수 있습니다.
2015년 연구에 따르면, L-시스테인을 전신 투여하면 가성 각막부종 환자의 각막 상피에서 일부 염증 매개체의 발현이 단백질 수준에서 증가한다는 사실이 밝혀졌습니다.
현재 수포성 각막염의 치료법에는 한계가 있습니다. 대증요법은 초기 단계에서만 효과적이며, 근본적인 원인을 해결하지 못하고 장기적인 해결책을 제공하지 못합니다. 각막 이식은 표준적인 방법이지만 감염, 기증자 각막 거부반응, 장기적인 면역억제제 복용 등의 위험을 수반합니다. 또한, 이식 수요 증가는 전 세계적으로 기증자 조직 부족을 악화시키고 있습니다. 이러한 문제를 극복하고 질병 관리를 강화하기 위해서는 각막 내피 재생 기술을 개선하고 새로운 치료법을 개발하기 위한 연구가 필수적입니다.
본 보고서는 주요 7개국의 수포성 각막염 시장에 대해 조사했으며, 시장 개요, 역학, 환자 동향, 새로운 치료법, 2034년까지 시장 규모 예측, 미충족 의료 수요 등을 정리하여 전해드립니다.
DelveInsight's "Bullous Keratopathy Market Insights, Epidemiology, and Market Forecast - 2034" report delivers an in-depth understanding of bullous keratopathy, historical and forecasted epidemiology, as well as the bullous keratopathy market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.
The Bullous Keratopathy Treatment Market Report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM bullous keratopathy market size from 2020 to 2034. The report also covers bullous keratopathy treatment market practices/algorithms and unmet medical needs to curate the best opportunities and assess the market's potential.
Bullous Keratopathy Treatment Market: Understanding and Algorithm
The term keratopathy comes from the root words Kera, meaning cornea, and pathy, meaning disease; therefore, keratopathy is the disease of the cornea with a vast array of underlying causes and mechanisms. Keratopathy can occur due to an eye condition or systemic conditions. There are several types of keratopathy, including bullous keratopathy. Bullous keratopathy is a pathological condition in which small vesicles, or bullae, formation occurs in the cornea due to endothelial dysfunction. Initially, there is endothelial trauma, followed by progressive stromal and epithelial edema. The epithelial edema results in the formation of bullae, hence the name bullous keratopathy.
Bullous keratopathy is also called pseudophakic bullous keratopathy (PBK) or pseudophakic corneal edema (PCE) in certain cases because it specifically occurs in individuals who have undergone cataract surgery and have had an IOL implanted in their eye. The main characterization is the formation of fluid-filled blisters or bullae on the cornea, which can cause pain, blurred vision, and other visual disturbances. This condition typically occurs due to damage to the corneal endothelium, the innermost layer of cells that maintains the cornea's clarity and controls fluid balance.
Bullous keratopathy diagnosis
Diagnosis of bullous keratopathy typically involves a comprehensive eye examination, including visual acuity testing, slit-lamp examination, and evaluation of corneal thickness and clarity. In some cases, additional tests such as corneal topography or specular microscopy are required to assess the severity and extent of corneal damage.
Bullous keratopathy Treatment
The treatment options for bullous keratopathy depend on the underlying cause and the severity of the condition. In the early stages, conservative measures to manage symptoms, such as lubricating eye drops, hyperosmotic agents, anti-glaucoma medications, steroids, ointments, or bandage contact lenses, are used to relieve pain and protect the cornea. The approval of allogeneic cell therapy in Japan may prove to be effective. However, if the condition progresses and significantly affects vision and quality of life, surgical intervention may be necessary.
Corneal transplantation, specifically endothelial keratoplasty (EK) procedures like Descemet's stripping automated endothelial keratoplasty (DSAEK) or Descemet's membrane endothelial keratoplasty (DMEK), is a common surgical option for bullous keratopathy. These procedures involve replacing the damaged corneal endothelium with healthy donor tissue to restore corneal clarity and improve visual function.
As the market is derived using a patient-based model, the bullous keratopathy epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by total cases of major etiologies of bullous keratopathy, total cases of bullous keratopathy in major etiologies, total diagnosed prevalent cases of bullous keratopathy , gender-specific diagnosed prevalent cases of bullous keratopathy, total cases of bullous keratopathy in corneal transplant/keratoplasty in the 7MM covering the United States, EU4 countries (Germany, France, Italy, and Spain) and the United Kingdom, and Japan from 2020 to 2034.
The drug chapter segment of the Bullous Keratopathy therapeutics market report encloses a detailed analysis of bullous keratopathy-marketed drugs and mid to late-stage (Phase III and Phase II) Bullous Keratopathy pipeline drugs analysis. It also helps understand the bullous keratopathy clinical trials details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug, and the latest Bullous Keratopathy news and press releases.
Bullous Keratopathy Marketed Drugs
VYZNOVA, developed by Aurion Biotechnologies, is a cell therapy indicated for treating bullous keratopathy of the cornea in Japan. VYZNOVA consists of allogeneic human corneal endothelial cells, referred to as "neltependocel", and Y-27632, a small molecule drug that inhibits Rho-associated, coiled-coil containing protein kinase. This combination facilitates the regeneration of fully differentiated corneal endothelial cells (CECs) outside the body. Donor corneal cells undergo a proprietary, multi-step process to create off-the-shelf allogeneic CECs. These cells are injected into the eye, where they form a healthy mono-layer and reduce corneal edema by removing excess fluid.
In March 2023, Japan's Pharmaceuticals and Medical Devices Agency (PMDA) approved VYZNOVA to treat bullous keratopathy of the cornea.
Bullous Keratopathy Emerging Drugs
TTHX1114 (NM141) is an engineered form of fibroblast growth factor-1 protein (FGF-1). The native FGF-1 is a potent stimulator of cell proliferation and migration and has cell-protective properties. The compound uniquely activates all seven forms of the FGF receptor, contributing to its potency; however, the naturally occurring FGF-1 molecule has an extremely short half-life. The engineered FGF-1, TTHX1114, is designed to increase the half-life of the FGF-1 molecule and stimulate the proliferation and migration of corneal endothelial cells.
TTHX1114 is intended to restore vision in patients with corneal endothelial diseases, including pseudophakic bullous keratopathy. It is being developed as an intracameral injection, which involves injecting a small amount of TTHX1114 into the anterior chamber of the eye (directly behind the cornea) using a very small needle.
In April 2023, Trefoil Therapeutics presented Phase II results for TTHX1114 in patients with Fuchs endothelial corneal dystrophy (FECD) undergoing Descemet's Stripping Only (DSO) in combination with cataract surgery at the Annual Association for Research in Vision and Ophthalmology (ARVO) Meeting.
EO2002 is a first-in-class, non-surgical, magnetic cell-based therapy that can modify disease, developed through an exclusive magnetic cell delivery (MCD) nanoparticle platform. The MCD platform facilitates the delivery, retention, and integration of cell therapies by leveraging magnetic nanoparticles to effectively localize and integrate cell therapies to the appropriate target tissue.
In April 2024, Emmecell completed the final dose administration for the last patient in the US randomized, double-masked, multi-center Phase I trial assessing the safety and efficacy of EO2002 for treating corneal edema. Topline results are expected in the second half of 2024, with a Phase III pivotal study planned for the first quarter of 2025.
Bullous Keratopathy Drugs Market Insights
The current Bullous Keratopathy treatment market landscape involves both pharmacological and surgical therapies. Medicinal interventions such as cell therapy, hypertonic saline drops and ointment (sodium chloride 5%), antibiotics, anti-inflammatories, antiglaucoma, lubricating drops, and other medications are used for symptomatic relief. However, medical management is only favorable in the early stages of the disease, and when it fails, surgery is considered.
Cornea transplant remains the gold standard of treatment for bullous keratopathy, which requires the replacement of damaged endothelium with a healthy endothelium from a donor to restore the normal structure and function of endothelial cells; however, visual recovery takes some time. The graft size is usually 7-7.5 mm to avoid complications of small and large grafts, such as astigmatism and secondary glaucoma.
Hydrophilic contact lenses are widely used to decrease pain associated with epithelial bullae; however, they do not reduce the amount of edema. The contact lenses can be used with 5% hypertonic saline to improve visual acuity by decreasing epithelial and stromal edema. Usually, the pain associated with PBK arises from the rupture of bullae with exposure of corneal nerves endings or swelling of epithelium leading to stretching of nerve endings, and the lenses alleviate pain as long as the lens remains in place by acting as an effective precorneal protective layer.
The approval of the first allogenic cell therapy globally marked a significant advancement in the treatment of corneal endothelial disease. In March 2023, PMDA approved VYZNOVA for treating bullous keratopathy of the cornea. The therapy addresses the need for non-surgical intervention and overcomes the donor cornea shortage by treating more than 100 eyes with fully differentiated CECs from a single donor. Healthy cells from a donor cornea are cultured in a novel, multi-step, proprietary, and patented process that produces off-the-shelf, allogeneic, fully differentiated CEC. Further, the endothelial cells are administrated intracamerally, where a repopulation of cells into a healthy monolayer occurs. Removing fluid from the cornea starts leading to the reduction of corneal edema.
A 2015 study demonstrated an increased expression of several pro-inflammatory mediators at the protein level in the corneal epithelium in patients with pseudophakic corneal edema when treated with systemic L-cysteine.
Current Bullous Keratopathy treatment options have limitations. Symptomatic treatments are effective only in the early stages and do not address the root cause or offer a long-term solution. Corneal transplantation, while standard, carries risks like infection, donor cornea rejection, and the need for long-term immunosuppressants. Additionally, increased transplant demand worsens the global donor tissue shortage. Advancing research, refining corneal endothelial regeneration techniques, and developing new therapies are essential to overcoming these challenges and enhancing disease management.
This section focuses on the uptake rate of potential Bullous Keratopathy drugs expected to be launched in the market during 2020-2034.
Bullous Keratopathy Pipeline Development Activities
The Bullous Keratopathy therapeutics market report provides insights into different therapeutic candidates in Phase III, Phase II, and Phase I. It also analyzes key players involved in developing targeted therapeutics.
Pipeline Development Activities
The Bullous Keratopathy therapeutics market report covers information on collaborations, acquisitions and mergers, licensing, and patent details for emerging therapies for bullous keratopathy.
KOL Views
To keep up with current market trends, we take KOLs and SMEs' opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry Experts contacted for insights on bullous keratopathy evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, and drug uptake, along with challenges related to accessibility, including Medical/scientific writers, Medical Professionals, Professors, Directors, and Others.
DelveInsight's analysts connected with 50+ KOLs to gather insights; however, interviews were conducted with 15+ KOLs in the 7MM. Centers like the University of Texas Health Science Center, Illinois College of Optometry and Salus University in the US, Eberhard-Karls-University Tubingen in Germany, University of Manchester and the Manchester Royal Eye Hospital in the UK, and Juntendo University Shizuoka Hospital in Japan, were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns or bullous keratopathy market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.
Physician's View
As per the KOLs from the US, standardized guidelines are urgently required as there are no guidelines for an accurate diagnosis and management of bullous keratopathy. An understanding of the precipitating causes and the Etiopathogenesis will further help in framing a curative treatment regimen. As per the KOLs from the UK, despite significant advancements in treating corneal endothelial disease, including improvements from traditional endothelial keratoplasty to DSEK, DMEK grafts, and injectable endothelial treatments, corneal disease remains a major global cause of blindness.
As per the KOLs from Japan, bullous keratopathy most commonly develops following glaucoma surgery, although it can also occur after complicated cataract surgery and laser iridotomy. Additionally, old age is a significant risk factor, as endothelial cell count decreases with advancing age.
Qualitative Analysis
We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT and Conjoint Analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of disease diagnosis, patient awareness, patient burden, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided. These pointers are based on the Analyst's discretion and assessment of the patient burden, cost analysis, and existing and evolving treatment landscape.
Conjoint Analysis analyzes multiple emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, route of administration, and order of entry. Scoring is given based on these parameters to analyze the effectiveness of therapy. To analyze the effectiveness of these therapies, have calculated their attributed analysis by giving them scores based on their ability to improve atrial and ventricular dimension/function and ability to regulate heart rate.
Further, the therapies' safety is evaluated wherein the adverse events are majorly observed, and it sets a clear understanding of the side effects posed by the drug in the trials, which directly affects the safety of the molecule in the upcoming trials. It sets a clear understanding of the side effects posed by the drug in the trials. In addition, the scoring is also based on the route of administration, order of entry and designation, probability of success, and the addressable patient pool for each therapy. According to these parameters, the final weightage score and the ranking of the emerging therapies are decided.
Bullous Keratopathy Therapeutics Market Access and Reimbursement
Although VYZNOVA is approved in Japan for treating bullous keratopathy, the US and EU markets crave licensed therapies. The current treatment relies on symptomatic management and surgical interventions. However, the costs associated with corneal transplantation, including pre-operative evaluations, surgical fees, postoperative care, and long-term medication use, pose financial burdens for patients. Hence, limiting access to treatment for individuals with limited financial resources or inadequate insurance coverage. Therefore, access to affordable treatments and interventions is a significant concern for individuals with bullous keratopathy. Developing cost-effective therapies and ensuring their availability to a broader population can reduce the burden on patients and healthcare systems.
Corneal transplant coverage
A corneal transplant is usually covered by private medical insurance and Medicare when deemed medically necessary. Out-of-pocket costs may include a specialty copay, a hospital copay, and coinsurance of 10-50% for the procedure up to the yearly out-of-pocket maximum allowance. Capital BlueCross considers corneal transplantation medically necessary for patients with bullous keratopathy. Similarly, Blue Cross Blue Shield of Massachusetts considers DSEK, DSAEK, DMEK, or DMAEK medically necessary to treat endothelial dysfunction, including bullous keratopathy.
PacificSource provides coverage for AMT, but prior authorization is required. PacificSource considers AMT or limbal stem cell transplantation for ocular surface reconstruction medically necessary when ALL following criteria are met:
A. Reconstruction of the corneal surface, as indicated for one of the following conditions:
B. Reconstruction of the surface of the conjunctiva, as indicated for one of the following conditions:
The Bullous Keratopathy therapeutics market report provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenarios, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.
Bullous Keratopathy Therapeutics Market Report Scope
Bullous Keratopathy Therapeutics Market Insights
Bullous Keratopathy Epidemiology Insights
Current Bullous Keratopathy Treatment Market Scenario, Marketed Drugs, and Emerging Therapies