PUBLISHER: DelveInsight | PRODUCT CODE: 1173615
PUBLISHER: DelveInsight | PRODUCT CODE: 1173615
DelveInsight's 'Hypophosphatasia - Market Insights, Epidemiology, and Market Forecast-2032' report delivers an in-depth understanding of the Hypophosphatasia, historical and forecasted epidemiology as well as the Hypophosphatasia market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.
The Hypophosphatasia market report provides current treatment practices, emerging drugs, market share of individual therapies, and the current and forecasted 7MM Hypophosphatasia market size from 2019 to 2032. The Report also covers current Hypophosphatasia treatment practice, SWOT analysis, reimbursement, market access, and unmet medical needs to curate the best of the opportunities and assesses the underlying potential of the market.
Study Period: 2019-2032.
Hypophosphatasia is defined as a rare, inherited metabolic disorder characterized by poor mineralization of bones and teeth, according to National Organization for Rare Disorders (NORD). Defective mineralization causes fragile, fracture-prone, and deformed bones, which also result in tooth loss. It can be inherited autosomally recessively or dominantly, depending on the specific form.
It is a multi-systemic metabolic disorder caused by loss-of-function mutations in the ALPL gene that encodes the mineralization-associated enzyme, tissue-nonspecific alkaline phosphatase (TNSALP). TNSALP regulates mitochondrial function and ATP levels. Defects in TNSALP are linked to mitochondrial dysfunction, cell respiration, and an increase in reactive oxygen species, which results in metabolic abnormalities in the group.
A heterogeneous inherited disorder of bone metabolism, it has a very varied clinical expression. It is characterized by defective bone and dental mineralization, leading to skeletal abnormalities with complications resulting in significant morbidity and mortality. The phenotypes range from the complete absence of bone mineralization and fetal death, mainly due to respiratory problems associated with thoracic deformities and pulmonary hypoplasia, to spontaneous fractures, premature tooth loss, seizures, or even nephrocalcinosis.
Based on various manifestations and severity, it is subdivided from the most severe to the mildest forms as perinatal, infantile, childhood-onset, adult, odonto Hypophosphatasia, and benign perinatal Hypophosphatasia.
Hypophosphatasia is diagnosed by identifying its symptoms and complications and understanding the patient history. Hypophosphatasia signs are revealed by a thorough clinical examination, supported by routine x-rays and various laboratory tests, including biochemical studies, alkaline phosphatase (ALP) assay, and blood and urine tests, among others. Serum alkaline phosphatase activity is markedly reduced while 5'pyridoxal phosphate in the blood and urinary phosphoethanolamine increase. Ultrasound is done for prenatal and perinatal forms; clinical examinations and radiographs help establish infantile, childhood, and adult diagnoses.
Hypophosphatasia is an underdiagnosed disease, and the prevalence of less severe or moderate forms of Hypophosphatasia is not accurately established. Further, the presentation and severity of the disease are highly variable from perinatal-onset Hypophosphatasia with mortality rates as high as 100% to adult-onset with little mortality but a high disease burden. Adult Hypophosphatasia typically presents during middle age and is often misdiagnosed or missed in practice.
Until recently, the treatment was mostly symptomatic and supportive, depending upon clinical manifestation. NSAIDs or glucocorticoids were majorly recommended to treat bone and joint pain due to the deposition of calcium pyrophosphate or hydroxyapatite crystals. They are still recommended to improve bone, joint or persistent pain secondary to fractures. Vitamin B6 and vitamin D are recommended for seizure control and supplementation. Potassium and phosphate binders and ACE inhibitors are also recommended.
Additional supportive therapies include ventilatory support, physiotherapy, occupational therapy, chronic pain management, and fracture care. Some cases, like nonhealing fractures or craniosynostosis, require surgical intervention. However, with the approval, the treatment paradigm for Hypophosphatasia has changed making ERT the mainstay treatment for at least all severe forms of the disease.
Almost a demi decade ago, the first line of therapy for Hypophosphatasia, STRENSIQ (asfotase alfa), developed by AstraZeneca (Alexion AstraZeneca Rare Disease), was approved by the US FDA (2015). It is recommended as the mainstay treatment for individuals with perinatal, infantile, and juvenile-onset Hypophosphatasia. The drug is also approved in Europe for treating patients with pediatric-onset Hypophosphatasia and in Japan for treating patients with Hypophosphatasia.
STRENSIQ is an ERT using bone-targeting recombinant alkaline phosphatase, addressing the main cause for manifestation. It improves skeletal mineralization, motor capabilities, and respiratory function while reducing mortality compared to historically untreated patients with more-severe perinatal, infantile, and childhood forms of Hypophosphatasia.
The disease epidemiology covered in the report provides historical as well as forecasted epidemiology segmented by Diagnosed Prevalent cases of Hypophosphatasia and Severity-specific Diagnosed Prevalent cases of Hypophosphatasia scenario of Hypophosphatasia in the 7MM covering the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan from 2019 to 2032.
The epidemiology segment also provides the Hypophosphatasia epidemiology data and findings across the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.
The drug chapter segment of the Hypophosphatasia report encloses a detailed analysis of Hypophosphatasia marketed drugs, mid-phase, and late-stage pipeline drugs. It also helps to understand the Hypophosphatasia clinical trial details, expressive pharmacological action, agreements and collaborations, approval, and patent details of each included drug, and the latest news and press releases.
STRENSIQ (asfotase alfa), developed by Alexion Pharma (now acquired by AstraZeneca), is a TNSALP indicated for the treatment of patients with perinatal, infantile- and juvenile-onset Hypophosphatasia.
It is a soluble glycoprotein composed of two identical polypeptide chains, which consists of the catalytic domain of human TNSALP, the human immunoglobulin G1 Fc domain, and a deca-aspartate peptide used as a bone targeting domain. It is an enzyme replacement therapy that replaces the TNSALP enzyme, the deficiency of which leads to elevations in several TNSALP substrates, including inorganic pyrophosphate (PPi). Elevated extracellular levels of PPi block hydroxyapatite crystal growth that inhibits bone mineralization and causes an accumulation of unmineralized bone matrix which manifests as rickets and bone deformation in infants and children and as osteomalacia. Replacement of the enzyme upon STRENSIQ treatment reduces the enzyme-substrate levels.
Human bone marrow-derived mesenchymal stem cells (MSCs) developed by PuREC Co., Ltd., clarified the use of antibodies that recognize two types of cell surface markers, LNGFR (CD271) and Thy1 (CD90), enabled extremely efficient sorting of human MSCs. PuREC specializes in regenerative cell therapy using MSCs. Advancements in human bone marrow cell isolation have led to the extraction of an extremely pure and rapidly expanding MSC population. REC (rapidly expanding cells) exhibit improved self-renewal and multilineage differentiation, which is highly relevant to cell therapy. In parallel, an initial clinical study infusing MSCs in patients with severe Hypophosphatasia has shown improvement in bone mineralization and bone function. Currently, Phase I/II clinical study in Japan is being led by Shimane University with a Japanese government grant (AMED (Japan Agency for Medical Research and Development)) and key hospitals using PuREC's REC.
ALXN1850 developed by AstraZeneca is an ERT replacing deficient ALP activity and targets ALP substrates to improve bone mineralization and ameliorate systemic manifestations of the disease. It is a next-generation Hypophosphatasia therapy designed to provide higher activity, higher bioavailability, and longer half-life than STRENSIQ (asfotase alfa). These improvements may result in significant benefits for Hypophosphatasia patients, including potentially lower, less frequent doses, improved efficacy, and lower injection volumes compared to STRENSIQ. Recently ALXN1850 has completed its Phase I trial, and Alexion, AstraZeneca Rare Disease is planning to initiate a Phase III trial of ALXN1850 in 2023.
ARU-2801 is a one-time, adeno-associated virus (AAV) gene therapy designed to deliver potentially curative efficacy to patients with Hypophosphatasia without the limitations of chronic administration. Data from preclinical studies with ARU-2801 showed improved disease biomarkers and increased survival. Preclinical research showed that treatment with ARU-2801 resulted in sustained elevation of tissue nonspecific alkaline phosphatase (TNAP), the missing enzyme in Hypophosphatasia, at levels that ameliorate disease symptoms. Manufacturing process development and Investigational New Drug (IND) application-enabling studies are currently underway.
Hypophosphatasia is a rare, genetic, metabolic disorder caused by autosomal recessive mutations or a single dominant-negative mutation in the ALPL gene found on chromosome 1 encoding TNSALP. It is a heterogeneous disease with high variability in disease presentation and severity, ranging from perinatal-onset with mortality as high as 100% to adult-onset with little mortality but a high disease burden.
Until recently, the treatment was mostly symptomatic and supportive, depending upon clinical manifestation. NSAIDs or glucocorticoids were majorly recommended to treat bone and joint pain due to the deposition of calcium pyrophosphate or hydroxyapatite crystals. They are still recommended to improve bone, joint or persistent pain secondary to fractures. Vitamin B6 and vitamin D are recommended for seizure control and supplementation. Potassium and phosphate binders and ACE inhibitors are also recommended.
Additional supportive therapies include ventilatory support, physiotherapy, occupational therapy, chronic pain management, and fracture care. Some cases, like nonhealing fractures or craniosynostosis, require surgical intervention. However, with the approval, the treatment paradigm for Hypophosphatasia has changed making ERT the mainstay treatment for at least all severe forms of the disease.
Almost a demi decade ago, the first line of therapy for Hypophosphatasia, STRENSIQ (asfotase alfa), developed by AstraZeneca (Alexion AstraZeneca Rare Disease), was approved by the US FDA (2015). It is recommended as the mainstay treatment for individuals with perinatal, infantile, and juvenile-onset Hypophosphatasia. The drug is also approved in Europe for treating patients with pediatric-onset Hypophosphatasia and in Japan for treating patients with Hypophosphatasia.
The approved product has given Alexion a major first-mover advantage as it quenched the need for therapy, giving it a monopoly in the market where its need for therapy counterbalances the high cost.
Despite ERT and supportive treatment, Hypophosphatasia still is a disease with high morbidity and mortality. There is a need for curative therapy, an alternative to the current treatment of multiple injections of medication per week, often associated with injection-site reactions, to maintain their health. Though the late-stage pipeline for Hypophosphatasia is not vibrant and active, there are several early-stage products like an ENPP1 inhibitor to reduce levels of PPi, a next-generation ERT with improved activity, bioavailability, half-life, a recombinant alkaline phosphatase, regenerative cell therapy using MSCs for treatment beyond infantile Hypophosphatasia, and gene therapies to provide a potential curative alternative to ERT. Though it is too early to be overambitious about the success of these products, they can address the many shortcomings associated with the current treatment and end the monopoly in the market for Hypophosphatasia.
According to DelveInsight, the overall dynamics of the Hypophosphatasia market is anticipated to change in the coming years owing to the expected launch of emerging therapies.
This section provides the total Hypophosphatasia market size and market size by therapies in the United States.
The total Hypophosphatasia market size and market size by therapies in EU4 (Germany, France, Italy, and Spain) and the United Kingdom are provided in this section.
The total Hypophosphatasia market size and market size by therapies in Japan are provided.
This section focuses on the rate of uptake of the potential drugs recently launched in the Hypophosphatasia market or expected to get launched in the market during the study period 2019-2032. The analysis covers the Hypophosphatasia market uptake by drugs; patient uptake by therapies; and sales of each drug.
This helps in understanding the drugs with the most rapid uptake, and the reasons behind the maximal use of new drugs and allows, the comparison of the drugs based on market share and size which again will be useful in investigating factors important in market uptake and in making financial and regulatory decisions.
The report provides insights into different therapeutic candidates in the phase II, and phase III stages and also analyzes key players involved in developing targeted therapeutics.
The report covers detailed information on collaborations, acquisitions, mergers, licensing, and patent details for Hypophosphatasia emerging therapies.
Approaching reimbursement proactively can have a positive impact both during the late stages of product development and well after product launch. In the report, we consider reimbursement to identify economically attractive indications and market opportunities. When working with finite resources, the ability to select the markets with the fewest reimbursement barriers can be a critical business and price strategy.
We perform competitive and market Intelligence analysis of the Hypophosphatasia market by using various competitive intelligence tools that include-SWOT analysis, PESTLE analysis, Porter's five forces, BCG Matrix, Market entry strategies, etc. The inclusion of the analysis entirely depends upon the data availability.