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¼¼°è ÁÖ¿ä 7°³±¹ÀÇ ÁøÇ༺ ÇÙ»ó¼º ¸¶ºñ(Progressive Supranuclear Palsy) ½ÃÀåÀ» Á¶»çÇßÀ¸¸ç, ½ÃÀå ÁÖ¿ä ¿ä¾à°ú ´õºÒ¾î ¿ªÇÐ, ȯÀÚ µ¿Çâ, »õ·Î¿î Ä¡·á¹ý, 2032³â ½ÃÀå ±Ô¸ð ¿¹Ãø, ÀÇ·á ¹ÌÃæÁ· ¿ä±¸ µîÀ» Á¦°øÇÕ´Ï´Ù.
DelveInsight's "Progressive Supranuclear Palsy - Market Insights, Epidemiology, and Market Forecast - 2032" report delivers an in-depth understanding of the progressive supranuclear palsy historical and forecasted epidemiology as well as the market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.
The progressive supranuclear palsy market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted the 7MM progressive supranuclear palsy market size from 2019 to 2032. The report also covers current progressive supranuclear palsy treatment practices/algorithms and unmet medical needs to curate the best opportunities and assess the market's potential.
Study Period: 2019-2032.
Progressive supranuclear palsy (PSP), also known as Steele-Richardson-Olszewski and Parkinson-plus syndrome, is a rare neurodegenerative disorder and the most common atypical Parkinsonism. It belongs to a group of diseases called tauopathies. The exact cause of progressive supranuclear palsy is unknown. However, it is believed to involve the abnormal accumulation of tau protein in certain areas of the brain, particularly the basal ganglia and brainstem, forming abnormal tangles, leading to the degeneration of brain cells.
It typically begins around the age of 60, and the symptoms gradually worsen over time. It is often characterized by the gradual deterioration of movement, balance, and coordination, dysphagia, impairment of cognitive functions, the control of eye movements, and others.
Progressive supranuclear palsy encompasses several phenotype variants; Richardson's syndrome is the most common phenotype of progressive supranuclear palsy, accounting for more than 50% of cases. It is characterized by a combination of Parkinsonism (similar to Parkinson's disease) and vertical gaze palsy (difficulty moving the eyes vertically). Other features may include postural instability, falls, early speech and swallowing difficulties, cognitive impairment, and behavioral changes. Progressive supranuclear palsy-Parkinsonism phenotype primarily presents with Parkinsonian features similar to Parkinson's disease. Patients exhibit bradykinesia (slowness of movement), rigidity, and tremor.
Other phenotypes include progressive supranuclear palsy with the predominant frontal presentation, corticobasal syndrome, and pure akinesia with gait freezing. The most frequent comorbidities observed in progressive supranuclear palsy patients are nervous system disorders, connective tissue diseases, eye disorders, and non-traumatic joint disorders.
Progressive supranuclear palsy is a progressive and ultimately debilitating disease. The progression of symptoms varies among individuals but generally worsens over time. The average life expectancy after progressive supranuclear palsy diagnosis is typically around 5-10 years, although survival can vary depending on individual factors and the age at onset.
Diagnosing progressive supranuclear palsy is challenging because its symptoms overlap with other movement disorders like Parkinson's disease, frontotemporal dementia, and corticobasal degeneration. There is no specific test for progressive supranuclear palsy, and diagnosis is usually based on the presence of characteristic symptoms, clinical examination, and ruling out other possible causes. Brain imaging, such as MRI, may support the diagnosis by showing specific patterns of brain atrophy.
Currently, two diagnostic criteria known as the MDS-PSP and NINDS-SPSP are widely used to diagnose progressive supranuclear palsy. MDS-PSP criteria include specific clinical and supportive features that help differentiate progressive supranuclear palsy from other disorders and establish an early diagnosis.
The current treatment landscape lacks approved products and clinical guidelines. The treatment focuses on managing symptoms, providing supportive care, and enhancing the quality of life. Several medications like levodopa, dopamine agonists, antidepressants, and others used for treating Parkinson's disease and other related disorders may help improve the symptoms of progressive supranuclear palsy.
Levodopa is commonly used to manage the Parkinsonian symptoms of progressive supranuclear palsy, such as bradykinesia, rigidity, and tremors. However, the response is often less favorable, and the benefits may be limited or short-lived. Further, dopamine agonists, such as amantadine and ropinirole, may be prescribed in conjunction with or as an alternative to levodopa.
Selective serotonin reuptake inhibitors (SSRIs) or other antidepressant medications manage depression and mood-related symptoms associated with progressive supranuclear palsy. Several other medications, including hypnotics and anxiolytics, botulinum toxin, anti-inflammatories, and antiepileptics, are also used for different symptoms of progressive supranuclear palsy. Further, physical therapy for mobility and balance, occupational therapy to assist with daily activities, and speech therapy to address speech and swallowing difficulties are also included.
As the market is derived using a patient-based model, the progressive supranuclear palsy epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by prevalent cases of progressive supranuclear palsy, diagnosed prevalent cases of progressive supranuclear palsy, gender-specific cases of progressive supranuclear palsy, phenotype-specific cases of progressive supranuclear palsy, and comorbidities associated with progressive supranuclear palsy in the 7MM covering the United States, EU4 countries (Germany, France, Italy, and Spain) and the United Kingdom, and Japan from 2019 to 2032.
The drug chapter segment of the progressive supranuclear palsy report encloses a detailed analysis of progressive supranuclear palsy, currently used drugs, and mid-stage (Phase II and Phase I) pipeline drugs. It also helps understand the progressive supranuclear palsy clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug, and the latest news and press releases.
BRAVYL is a small molecule, repurposed, oral version of fasudil, a potent inhibitor of Rho-kinases (ROCK) that are elevated in progressive supranuclear palsy and are involved in the accumulation of tau aggregates that lead to progressive supranuclear palsy.
ROCK is an enzyme important in mediating vasoconstriction and vascular remodeling in the pathogenesis of pulmonary hypertension. ROCK induces vasoconstriction by phosphorylating the myosin-binding subunit of myosin light chain (MLC) phosphatase, thus decreasing MLC phosphatase activity and enhancing vascular smooth muscle contraction.
ERIL, an IV formulation of fasudil, is approved in Japan for treating cerebral vasospasm and delayed cerebral ischemic symptoms after subarachnoid hemorrhage.
Embark Healthcare launched Woolsey Pharmaceutical, its portfolio company, toward the end of 2019. BRAVYL (fasudil) is currently being tested in Phase IIa clinical studies for progressive supranuclear palsy - Richardson's syndrome and CBS.
AZP2006 (ezeprogind) is an orally available small molecule with a novel mechanism of action and effects. It involves the action of a neurotrophic factor, which combines reinforced neuroprotective efficacy and anti-neuroinflammation activity.
AZP2006 blocks tau phosphorylation by stabilizing the prosaposin-progranulin complex. The stabilization prevents progranulin cleavage and increases progranulin secretion, further protecting the central neurons in progressive supranuclear palsy patients. Moreover, it also inhibits microglial activation and pro-inflammatory cytokine production.
AZP2006 has exceptional therapeutic potential to treat the physiopathological causes of progressive supranuclear palsy and other related tauopathies such as Alzheimer's disease. The company has completed the Phase IIa study to treat progressive supranuclear palsy and showed positive and promising results.
Alzprotect has received approval from the French National Agency for the Safety of Medicines and Health Products (ANSM) and the Ethical Review Board to extend the trial as an open-label for an additional 6 months for all eligible patients. Further, the company plans to initiate a larger pivotal Phase IIb/III by early 2024 in Europe and the US.
Note: Detailed emerging therapies assessment will be provided in the final report.
Progressive supranuclear palsy is a rare neurodegenerative disorder resulting from damage to nerve cell clusters called nuclei (supranuclear) in the brain, deteriorating balance while walking, speech difficulties, trouble in swallowing, changes in mood and behavior, and cognitive impairment. Progressive supranuclear palsy is characterized pathologically by four-repeat (4R) Tau deposition in various cell types and anatomical regions. The mean onset age is 63 years, and the mean survival is 6-9 years. No specific laboratory tests or imaging approaches exist to diagnose progressive supranuclear palsy definitively. The disease is often difficult to diagnose because its symptoms can be similar to those of other movement disorders and because some of the most characteristic symptoms may develop late or not. At present, therapeutic options for progressive supranuclear palsy are symptomatic and insufficient. Progressive supranuclear palsy symptoms usually do not respond to medications. Drugs prescribed to treat Parkinson's disease, such as levodopa, rarely provide additional benefits.
Several drug classes are being used off-label to manage various symptoms experienced by progressive supranuclear palsy patients. These include dopamine agonists, antidepressants, anti-inflammatories, antipsychotics, acetylcholinesterase inhibitors, hypnotics, and anxiolytics.
Selective serotonin reuptake inhibitors (SSRIs) or other antidepressant medications manage depression and mood-related symptoms associated with progressive supranuclear palsy. Several other medications, including hypnotics and anxiolytics, botulinum toxin, anti-inflammatories, and antiepileptics, are also used for different symptoms of progressive supranuclear palsy. Further, physical therapy for mobility and balance, occupational therapy to assist with daily activities, and speech therapy to address speech and swallowing difficulties are also included.
Further, muscle relaxants such as baclofen are primarily used in spasticity treatment. Although no controlled studies have evaluated their efficacy specifically for dystonia, they may be helpful in certain cases of progressive supranuclear palsy. Dosing starts at 5 mg once daily and generally titrates to 10 mg TID. However, baclofen may cause weakness, orthostatic hypotension, sedation, or confusion in patients with marginal gait function. Moreover, treatment with benzodiazepines (most commonly clonazepam starting at 0.25 mg daily, titrating to efficacy, toxicity, or 3 mg/day) may be attempted for dystonia in progressive supranuclear palsy.
Progressive supranuclear palsy, an atypical Parkinsonian condition, is characterized by a range of motor and behavioral syndromes associated with 4-repeat tau neuropathology. Early falls, supranuclear gaze palsy, axial and limb rigidity, and motor eyelid disorders are common disease symptoms. The typical age of disease onset is in the fifth to seventh decade of life. Several phenotypes of progressive supranuclear palsy have been defined over the past few years; PSP-RS, PSP-P, PSP-CBS, and PSP-PGF are a few common among them. Further, due to its complex presentation of phenotype and overlapping symptoms with neurodegenerative disorders, missed and delayed diagnosis is common and an obstacle in managing progressive supranuclear palsy. Similar symptoms in other neurological disorders complicate diagnosis and make differential diagnosis an imperative factor.
Nevertheless, progress has been made in terms of diagnosis; in 2017, the new MDS diagnostic criteria for progressive supranuclear palsy recognized early, suggestive forms of progressive supranuclear palsy and operationalized diagnosis of non-Richardson's progressive supranuclear palsy phenotypes. Earlier, the 1996 NINDS-SPSP criteria did not allow the recognition of variable phenotypic progressive supranuclear palsy presentations and early clinical manifestations.
The current treatment landscape lacks disease-modifying therapies and treatment guidelines. While symptomatic treatments are widely used, they only show mild to moderate efficacy. Although one medication does not treat all the symptoms of progressive supranuclear palsy, specific treatments may be helpful. To improve balance and the flexibility of the muscles, levodopa and amantadine, an antiparkinson medication, are widely used. However, Parkinson's medications are ineffective; only 20-30% respond well to levodopa. Besides antiparkinson drugs, antidepressants, anti-inflammatories, and other agents are used to relieve associated symptoms and conditions. In addition, eye drops are recommended for dry eyes to prevent exposure to keratitis, and botulinum toxin injections may reduce blepharospasm, dystonia, and retrocollis.
Levodopa (with a peripheral decarboxylase inhibitor such as carbidopa or benserazide) is the principal pharmacologic agent used for dopaminergic replacement therapy in progressive supranuclear palsy, with a more robust response generally seen in the PSP-P subtype. Bradykinesia, rigidity, and tremor seen in any phenotype of progressive supranuclear palsy may respond as well as in PSP-P, but postural instability is unlikely to respond. Based on retrospective studies, 20-30% of pathologically confirmed and 20-40% of clinically diagnosed progressive supranuclear palsy patients reported a beneficial response to levodopa alone or combined with another dopaminergic agent (such as amantadine). These responses generally occur early in the disease course and persist for only a few months. Furthermore, levodopa treatments are attempted only in patients with rigidity, bradykinesia, or tremor-impaired daily activities.
For Parkinsonism, a levodopa trial of up to 1,200 mg/d (up to 300 mg per dose if it can be tolerated) for 1 month is recommended to determine responsiveness. Dopamine agonists, however, often provide minimal benefit. In some cases, donepezil is also found to improve cognitive function in progressive supranuclear palsy; however, it has been reported to worsen motor symptoms. Despite several retrospective reports of clinically meaningful improvement in motor function on low doses of amitriptyline, these medications in progressive supranuclear palsy are not recommended due to their anticholinergic side effects and risk of exacerbating falling.
The current market has been covered by the symptomatic treatment that includes different pharmacological agents used across the 7MM, which presents minor variations in the overall prescription pattern. Levodopa, amantadine, amitriptyline, zolpidem, and botulinum toxin A are the major drugs considered for symptomatic treatment in the forecast model.
Key players Woolsey Pharmaceutical/Asahi Kasei Pharma (BRAVYL [fasudil]), AlzProtect (AZP2006 [ezeprogind), Transposon Therapeutics/Oncolys Biopharma (TPN-101/OBP-601 [censavudine]), and others are evaluating their lead candidates in different stages of clinical development. They aim to investigate their products for the treatment of progressive supranuclear palsy.
This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2019-2032. For example, Woolsey Pharmaceutical/Asahi Kasei Pharma's BRAVYL (fasudil), a potent inhibitor of Rho-kinases (ROCK), with an anticipated entry by 2027 in the US, is predicted to have a slow-medium uptake during the forecast period.
The report provides insights into therapeutic candidates in Phase II and Phase I. It also analyzes key players involved in developing targeted therapeutics.
The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for emerging therapies for progressive supranuclear palsy.
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 the progressive supranuclear palsy 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 Southern Illinois University School of Medicine, the University of Washington, the University Hospital of Tours, Navarra Institute for Health Research, the University of Tokyo School of Medicine, and the National Center of Neurology and Psychiatry were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns or progressive supranuclear palsy market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.
According to our primary research analysis, though there is a lack of treatment guidelines, levodopa and amantadine are used to alleviate rigidity and bradykinesia, while amitriptyline and zolpidem were mostly used to manage depression and dystonia, respectively. This botulinum toxin also manages dystonia, including blepharospasm and sialorrhea.
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.
The therapies' safety is evaluated wherein the acceptability, tolerability, and adverse events are majorly observed. 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.
Reimbursement of rare disease therapies can be limited due to lack of supporting policies and funding, challenges of high prices, lack of specific approaches to evaluating rare disease drugs given limited evidence, and payers' concerns about budget impact. The high cost of rare disease drugs usually has a limited effect on the budget due to the small number of eligible patients being prescribed the drug. The US FDA has approved several rare disease therapies in recent years. From a patient perspective, health insurance and payer coverage guidelines surrounding rare disease treatments restrict broad access to these treatments, leaving only a small number of patients who can bypass insurance and pay for products independently.
The 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.