Stem Cell Clinic

FROM THE LABS: Hispanic Heritage Spotlight: Interview with Dr. Nino Rainusso – Baylor College of Medicine News

By adminNovember 12, 2020Stem Cell Medicine

From the Labs sat down with Dr. Nino Rainusso, assistant professor of pediatrics hematology/oncology and a member of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine. Dr. Rainusso shared what inspired him to become a pediatric oncologist, his experience finding a research position in a Baylor lab and something few know about him.

I was born and raised in Per where I attended medical school at Universidad Peruana Cayetano Heredia. Early in my training I realized that if I wanted to better understand the medical conditions of my patients, I had to be involved in biomedical research. I wanted to become a physician-scientist in the field of pediatric neurology. This changed when I met my wife. Her brother had neuroblastoma, a common pediatric cancer that frequently develops in nerves associated with the adrenal glands located on top of the kidneys. When he died of the cancer, my career took a different path. Instead of spending my life as a pediatric neurologist, I became a pediatric oncologist.

During my rotations in medical school, I saw that doctors were exceptionally good at providing medical care for their patients but didnt have time to do research. That motivated me to come to the U.S. where I would have opportunities to continue my career as a physician-scientist.

After I completed my residency in general pediatrics at the University of Illinois at Chicago, I was accepted at Baylor for my fellowship in pediatric oncology. I dove into research in the second and third years. Having many patients with different types of tumors for which the treatment outcome has not significantly changed for the last 30 years meant that there was a wealth of research opportunities. One day, I attended a talk about cancer stem cells that inspired me to apply that approach to pediatric solid tumors.

I joined Dr. Jeff Rosens lab at Baylor. I liked his lab for its open-minded environment and collaborative atmosphere that many Baylor labs have.

I was not sure about what his response would be when I proposed to work in his group.

He has spent his entire life doing research in breast cancer and I, with little lab experience under my belt, was proposing to do research in osteosarcoma stem cells. Osteosarcoma is the most common bone cancer in children and young adults. I was expecting that he would try to change my mind, but instead he said, OK, welcome! I loved it! I am very grateful that I ended up working in Jeffs lab. He has been a wonderful mentor, and I learned a lot working in his group.

When it was time for me to have my own lab, I joined Dr. Jason Yusteins group at Texas Childrens Cancer & Hematology Centers. We took a new approach to study osteosarcoma. One limitation of studying this condition is working with cell lines, which do not seem to recapitulate most of the characteristics of tumors in patients.

We decided to generate patient-derived tumor xenografts models of pediatric sarcomas where the tissue from a patients tumor is implanted into immunosuppressed mice. These tumors closely resemble the characteristics of the original tumor allowing to have better understanding of cancer biology and to evaluate novel therapies.

We collaborate with other investigators to test new treatments such us immunotherapy in these xenograft models, which may put us a step closer to bringing more effective therapies to patients. I believe that our research would not be possible without the participation of multiple colleagues at Texas Childrens Hospital and the nurturing scientific environment provided by Baylor College of Medicine.

My close friends Alicia and Miguel are superb science teachers in a high school that serves economically disadvantaged communities.

Their schools have many dropouts and one of the reasons seems to be lack of opportunities for students to know what they could become.

Most students, not only Hispanics, are not aware of what scientists do or what a research lab looks like.

One idea could be to sponsor science fairs in these schools and award prizes that also include student tours of Baylor or Texas Childrens lab facilities. Students also need to be aware of scholarships they could apply for to pursue a higher education.

Finally, academic institutions and researchers may also participate in school talks to promote a better understanding of science and its direct repercussions in our daily life and to reduce the mistrust in science, which is a growing topic of significant concern.

I am a Star Wars fan so my office has many items from a galaxy far, far away.

By Ana Mara Rodrguez, Ph.D.

See the rest here:
FROM THE LABS: Hispanic Heritage Spotlight: Interview with Dr. Nino Rainusso - Baylor College of Medicine News

Protective protein could help keep blood young and healthy – New Atlas

By adminNovember 12, 2020Stem Cell Medicine

A new study led by the University of Edinburgh and Queen Mary University of London has identified a protein that plays a crucial role in protecting the bodys blood stem cells from damage during infection, a finding that could lead to new ways to slow down the aging process.

Hematopoietic stem cells (HSCs) are found in bone marrow, and from there they produce other blood and immune cells. When an infection strikes the body, HSCs are known to ramp up production to fight it off but thats raised some questions for scientists in the past. In particular, how do they protect themselves from damage while working overtime?

We know that inflammatory pathways induced by infection force blood stem cells to rapidly produce immune cells to help combat infections, says Kamil Kranc, corresponding author of the study. However, these pathways can eventually exhaust stem cells or cause their premature aging, and it is important to understand how this can be stopped.

In the new study, the researchers identified a protein called YTHDF2 that seems to be responsible for this important job. When an infection arises, the HSCs produce far more immune cells, but at the same time that triggers inflammatory processes that can damage the stem cells. The study found that the YTHDF2 protein regulates genes that control those inflammatory processes, protecting the stem cells from premature aging.

To investigate the role of YTHDF2, the team engineered mice to be deficient in the protein, then administered a chemical that acts like a viral infection. Sure enough, the mices HSCs appeared to suffer chronic inflammation, altering the production of different blood cell types. Interestingly, the blood of these young animals began to resemble that of much older mice.

The new study seems to agree with previous reports that blood transfusions from young animals to older ones can improve the health of the recipient, and even slow the progression of diseases like Alzheimer's. As such, the team says that future work could investigate whether manipulating levels of YTHDF2 may be a potential anti-aging treatment.

The research was published in the Journal of Experimental Medicine.

Source: University of Edinburgh

Continue reading here:
Protective protein could help keep blood young and healthy - New Atlas

Global Contract Cell and Gene Therapy Manufacturing Market 2020-2026: Automation Deployed to Contain Cost of Goods Sold and Vector Manufacturing…

By adminNovember 12, 2020Gene Therapy Clinics

November 12, 2020 07:48 ET | Source: Research and Markets

Dublin, Nov. 12, 2020 (GLOBE NEWSWIRE) -- The "Global Contract Cell and Gene Therapy Manufacturing Market 2020-2026 - Supply Chain Optimization and Decentralized Manufacturing to Expand the Industry" report has been added to ResearchAndMarkets.com's offering.

This research service focuses on the critical role being played by CDMOs in not only supporting new product research and development but also in creating standardized manufacturing protocols.

Additionally, the study explores different cross-sections of the market and discusses market dynamics for autologous and allogeneic solutions for cell and gene therapies and for products being manufactured for clinical trial use and for commercial markets. The variability in market dynamics, manufacturing protocols, and business models across cross-sections is high. Therefore, the study also covers the emergence of non-traditional CDMOs that have thrived as a result of this variability.

The cell and gene therapy segment is one of the fastest growing segments in the biopharmaceutical space. While the science behind the therapy has grown by leaps and bounds on the back of decades worth of research, manufacturing has unfortunately lagged behind.

To fully harness the curative potential of these therapies and ensure greater reach and affordability to patients, it is imperative that aggressive investments in manufacturing technology and capacity are made today. Investments in manufacturing technology advancements including automation, single-use technologies, and GMP-in-a-box, will not only enable operational efficiency gains but also reduce project costs, generating benefits which can be transferred directly to the patients.

A large part of this growth in the cell and gene therapy product pipeline is being driven by small and mid-sized biotechs that depend on CDMOs to mitigate product development risks and diffuse infrastructure investments to be able to build future products pipeline.

The study also provides a comprehensive and critical analysis of nationally coordinated efforts towards infrastructure development and the rise of academic institutes and hospitals in meeting not only the demand from clinics, but also the demand of the commercial market.

The study also analyses the growth of specialist CDMOs focusing on vectors and plasmids, for instance. This captures the regional outlook for growth based on the currently installed capacities as well as the pipeline investments being made towards expansion. Lastly, the study tracks growth opportunities across the entire product development spectrum from supply chain to upstream and downstream manufacturing.

Key Topics Covered:

1. Strategic Imperatives

2. Growth Opportunity Analysis - CGT CDMO Market

3. Growth Opportunity Universe - CGT CDMO Market

4. Next Steps

For more information about this report visit https://www.researchandmarkets.com/r/3obb4f

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

Formats available:

Read the rest here:
Global Contract Cell and Gene Therapy Manufacturing Market 2020-2026: Automation Deployed to Contain Cost of Goods Sold and Vector Manufacturing...

Gene Therapy Market Size Is Estimated to Grow at a CAGR of 40.7% By 2025 | Sales Statistics, Future Trends, Business Overview and COVID-19 Impact…

By adminNovember 12, 2020Gene Therapy Clinics

Gene Therapy Market Size, Growth and Share Analysis By Product (Kymriah, Luxturna, Yescarta, Zolgensma, Strimvelis, Zynteglo, Others), By Indication (Oncology, Genetic Diseases, Others) and By End-User (Hospitals & Clinics, Specialty Treatment Centers, Others) Forecast to 2025

Gene Therapy Market Synopsis

The GlobalGene Therapy Marketsize was recorded at a value of USD 524 million in 2018 and is touted to register a CAGR of 40.7%. Global gene therapy market growth in gene therapy is due to various factors such as a strong drug pipeline, increased investment by key players and a high prevalence of target disease, as well as demand for innovative drugs. Over recent years, the number of applications for gene therapy has risen, including the treatment of numerous rare and incurable disorders such as cancer, and genetic diseases inherited. With an advent in the number of molecules being tested across different clinical trials, the count is dominated by the trials intended to develop cancer therapies.

Research and development is driving global gene therapy alongside increased investment in product development. Growing policy funding for gene therapy studies, ethical approval of gene therapy for cancer treatment, and increasing incidence of cancer often fuel demand development for gene therapy. In addition, rapid and significant progress in the arena of molecular and cellular biology, driven by technological advances in genomics and gene-editing tools, has contributed to a growing number of approved gene therapies and an expanding pipeline.

Request Free Sample Copy of the report "Gene Therapy Market Research Report - Global Forecast till 2025" at: https://www.marketresearchfuture.com/sample_request/8399

Yet high cost of drug production and stringent regulatory regulations are likely to limit the expansion of the global demand for gene therapy. Today the global gene therapy market is dominated by many industry players. The key players are involved in product launches and strategic collaborations to strengthen their market positions.

Gene Therapy Market Segmental Analysis

The globalgene therapy markethas been segmented based on product, indication, and end user.

The product-based gene therapy market was divided up into kymriah, luxturna, yescarta, zolgensma, strimvelis, zynteglo, imlygic, and others.

The global gene therapy market is segmented into oncology, genetic diseases / disorders and others based on indication. The oncology sector is expected to have the largest market share and to be the fastest developing sector due to the high prevalence of cancer and robust pipeline for cancer gene therapy.

Segmentation by end users in the gene therapy market has been done into hospitals & clinics, specialist care centers, and more. Thanks to an growing number of clinics, the group Clinics & Clinics is expected to have the highest gene therapy market share. Hospitals are also generally the first choice for treating diseases.

Gene Therapy Market Regional Analysis

Region wise, the gene therapy market is analyzed across North America, Europe, Asia-Pacific, and LAMEA. North America accounted for the largest market share of gene therapy in 2018, and this pattern is predicted to continue throughout the projected period due to high cancer incidence, high disposable income and increased support for gene therapy-related R&D activities.

Asia-Pacific, however, is expected to record the highest growth over the forecast period, owing to an advent in the number of people prone to various chronic diseases. However, the approval and introduction of gene therapy drugs will have a positive effect on the growth of the gene therapy market in developing countries , such as Japan, Australia and New Zealand.

Browse Detailed TOC with COVID-19 Impact Analysis at:https://www.marketresearchfuture.com/reports/gene-therapy-market-8399

Increase in support for cell therapy and gene therapy companies through European countries including the UK. Europe 's economy is expected to expand at a lucrative pace. In addition, European companies are committed to expanding the distribution of goods globally by gaining approval from multiple regulatory bodies.

Gene Therapy Market Competitive Dashboard

Some of the eminent players in the globalgene therapy marketare Novartis AG (Switzerland), Amgen, Inc. (US), Spark Therapeutics, Inc. (US), CEVEC (Germany), Gilead Sciences, Inc. (US), uniQure N.V. (Netherlands), Orchard Therapeutics plc (UK), Bristol-Myers Squibb Company (US), Celgene Corporation (US), Thermo Fisher Scientific Inc. (US), and Lonza (Switzerland).

Browse More Related Research Reports at:

ThemHealth marketsize will grow at a CAGR of 36.5% and touch USD 21.71 Billion by 2022

About Market Research Future:

At Market Research Future (MRFR), we enable our customers to unravel the complexity of various industries through our Cooked Research Report (CRR), Half-Cooked Research Reports (HCRR), & Consulting Services. MRFR team have supreme objective to provide the optimum quality market research and intelligence services to our clients.

Media Contact Company Name: Market Research Future Contact Person: Abhishek Sawant Email: Send Email Phone: +1 646 845 9312 Address:Market Research Future Office No. 528, Amanora Chambers Magarpatta Road, Hadapsar City: Pune State: Maharashtra Country: India Website: https://www.marketresearchfuture.com/reports/gene-therapy-market-8399

Read this article:
Gene Therapy Market Size Is Estimated to Grow at a CAGR of 40.7% By 2025 | Sales Statistics, Future Trends, Business Overview and COVID-19 Impact...

Homology Medicines Announces Presentation of Positive Data from the Dose-Escalation Phase of the pheNIX Gene Therapy Trial for Adults with PKU -…

By adminNovember 12, 2020Gene Therapy Clinics

November 06, 2020 11:40 ET | Source: Homology Medicines, Inc.

- Marked Reductions in Phe Observed at Two Doses -

- Achieved Goal with Plans to Advance to Randomized, Concurrently Controlled Expansion Phase of Trial -

- Webcast / Conference Call Today, November 6 at 4:30 p.m. ET -

BEDFORD, Mass., Nov. 06, 2020 (GLOBE NEWSWIRE) -- Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today the presentation of positive data from the dose-escalation portion of the Phase 1/2 gene therapy pheNIX clinical trial for adults with phenylketonuria (PKU). The results showed that product candidate HMI-102 was generally well-tolerated, and resulted in marked reductions in phenylalanine (Phe) and the Phe-to-tyrosine (Tyr) ratio (Phe/Tyr ratio) at two doses. Phe is a registrable endpoint in PKU, and the Phe/Tyr ratio is a clinically relevant diagnostic measurement for PKU. With these positive results, Homology is progressing to the randomized, concurrently controlled expansion phase of the trial, which has the potential to be converted to a registrational trial.

The data were presented today in an oral presentation by Olaf Bodamer, M.D., Ph.D., FACMG, FAAP, Park Gerald Chair in Genetics & Genomics and Associate Chief of Genetics & Genomics at Boston Childrens Hospital, and principal investigator of the pheNIX trial, during the New England Consortium of Metabolic Programs (NECMP) annual meeting, which is focused on new research in metabolic disorders. NECMP includes metabolic clinics, healthcare providers, patient organizations and others dedicated to increasing knowledge of metabolic disorders and improving delivery of healthcare to patients.

This is the first-ever PKU gene therapy clinical trial, and I am excited to share these data with the PKU community as I believe they demonstrate the potential of HMI-102 to treat the underlying genetic cause and reduce the therapeutic burden for patients and their families, stated Dr. Bodamer. PKU is a challenging condition, and a treatment that establishes normal metabolism could change the prognosis for patients with this rare genetic disorder. We look forward to participating in the next phase of the study.

We are pleased to have met the goals of the dose-escalation portion of the trial, which were evaluation of safety and efficacy of a single I.V. administration of HMI-102 and dose determination for the expansion phase of the trial, stated Gabe Cohn, M.D., Chief Medical Officer of Homology Medicines. Even as many patients self-liberalized their diets, there were patients at the mid- and high-doses with plasma Phe values below 360 mol/L and/or 600 mol/L, and one of these patients achieved a Phe level within the normal range. This is the first time a genetic medicines approach has achieved these results in patients with PKU. We have learned a tremendous amount in the dose-escalation phase and are applying these learnings to the expansion phase of the trial, which we anticipate initiating in early 2021.

Dr. Cohn continued, We greatly appreciate the PKU community of patients, clinicians and caregivers who have participated in this first phase of the pheNIX trial, and we look forward to working together during the next phase.

As of the data cutoff date of October 19, 2020, six patients in the dose-escalation phase of the pheNIX trial had received gene therapy product candidate HMI-102 across three dose cohorts (low-dose Cohort 1, n=2; mid-dose Cohort 2, n=2; high-dose Cohort 3, n=2). Cohorts included males and females, with an age range of 21-49 and time in study ranging from 13 weeks to 52 weeks (end of study).

Safety Observations HMI-102 was generally well-tolerated, and there were no treatment-related serious adverse events (SAEs). There were no clinically significant changes in ECG or vital signs and no clinical signs of complement activation. The Grade 1 and 3* alanine aminotransferases (ALTs) observed in Cohorts 2 and 3, which is common in AAV-based gene therapy, were managed with increased steroids when necessary. The patients who experienced Grade 3 ALTs had pre-existing underlying immune conditions. An independent data monitoring committee, which provided guidance throughout the pheNIX trial, concluded that there were no safety concerns related to bilirubin, and that ALT elevations may be associated with reduced efficacy.

Updates to the expansion phase of the pheNIX trial, including key learnings related to patient selection, monitoring and steroid regimen, are being incorporated.

Efficacy Observations

Cohort 1 (Low-Dose) Through 52 weeks, patients in Cohort 1 continued to show no meaningful reductions in Phe.

Cohorts 2 and 3 (Mid- and High-Dose) The mean percent change from baseline in Phe observed in patients in Cohorts 2 and 3 were significant, compared to Cohort 1**. These Phe reductions occurred while patients self-liberalized their diets.

Through 48 weeks, one patient in Cohort 2 had Phe levels of <360 mol/L and/or <600 mol/L*** at multiple timepoints and had reached a minimum Phe level of 42 mol/L, compared with a baseline level of 1,010 mol/L. Through 13 weeks, one patient in Cohort 3 had a Phe level <360 mol/L and several Phe levels <600 mol/L at multiple timepoints and had reached a minimum Phe level of 303 mol/L, compared with a baseline level of 1,060 mol/L.

In Cohorts 2 and 3, Phe reductions were greater among patients with Grade 1 ALTs compared to patients with Grade 3 ALTs****; ALT elevations were managed with increased steroids when necessary. It appears higher ALT elevations may limit therapeutic activity, but can be managed with a modified steroid regimen, which is being incorporated into the expansion phase.

Expansion Phase Based on the safety and efficacy results observed in the dose-escalation phase, Homology is advancing to the randomized, concurrently controlled, dose expansion phase of the pheNIX trial, which has the potential to be converted to a registrational trial.

All cohorts in the dose-escalation phase showed an acceptable safety profile and certain patients in Cohorts 2 and 3 showed marked Phe reductions. Based on these collective data, Homology has selected two doses for the expansion phase: the mid-dose from Cohort 2 and a dose between the doses in Cohorts 2 and 3. The Company believes the latter dose has the potential to improve Phe reductions while reducing steroid exposure that was required at the high-dose. The Company believes that advancing two doses in parallel provides the potential to convert to a registrational trial quickly with the optimal dose as the expansion phase does not include staggered dosing between patients.

Webcast/Conference Call Homology management and Dr. Bodamer will host a conference call and webcast today, Friday, November 6 at 4:30 p.m. ET. The webcast will be accessible on Homologys website in the Investors section, and the webcast replay will be available on the website for 90 days following the presentation. To access using the conference call line, dial (866) 244-8091 (U.S./Canada toll-free) or (602) 563-8623, with Conference ID 7394503.

About HMI-102 HMI-102 is an investigational gene therapy in clinical development for the treatment of phenylketonuria (PKU) in adults. HMI-102 is designed to encode the PAH gene, which is mutated in people with PKU, delivered via the liver-tropic AAVHSC15 vector. Homology has received Fast Track Designation and orphan drug designation for HMI-102 from the U.S. Food and Drug Administration (FDA), and orphan drug designation from the European Medicines Agency (EMA).

About Phenylketonuria (PKU) PKU is a rare inborn error of metabolism caused by a mutation in thePAHgene. PKU results in a loss of function of the enzyme phenylalanine hydroxylase, which is responsible for the metabolism of phenylalanine (Phe), an amino acid obtained exclusively from the diet. If left untreated, toxic levels of Phe can accumulate in the blood and result in progressive and severe neurological impairment. Currently, there are no treatment options for PKU that target the underlying genetic cause of the disease. According to the National PKU Alliance, PKU affects nearly 16,500 people in the U.S. with approximately 350 newborns diagnosed each year. The worldwide prevalence of PKU is estimated to be 50,000 people.

About Homology Medicines, Inc. Homology Medicines, Inc. is a genetic medicines company dedicated to transforming the lives of patients suffering from rare genetic diseases with significant unmet medical needs by curing the underlying cause of the disease. Homologys proprietary platform is designed to utilize its human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to precisely and efficiently deliver genetic medicinesin vivoeither through a gene therapy or nuclease-free gene editing modality across a broad range of genetic disorders. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a particular focus on rare diseases, and intellectual property covering its suite of 15 AAVHSCs. Homology believes that its compelling preclinical data, scientific expertise, product development strategy, manufacturing capabilities and intellectual property position it as a leader in the development of genetic medicines. For more information, please visitwww.homologymedicines.com.

Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding our expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of our product candidates; plans and timing surrounding the Phase 1/2 pheNIX trial, including the expansion phase and the potential for conversion to a registrational trial; our position as a leader in the development of genetic medicines; and our participation in upcoming presentations and conferences. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the impact of the COVID-19 pandemic on our business and operations, including our preclinical studies and clinical trials, and on general economic conditions; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; failure to identify additional product candidates and develop or commercialize marketable products; the early stage of our development efforts; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the capabilities of our manufacturing facility; risks relating to the regulatory approval process; interim, topline and preliminary data may change as more patient data become available, and are subject to audit and verification procedures that could result in material changes in the final data; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; failure to obtain U.S. or international marketing approval; ongoing regulatory obligations; effects of significant competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; failure to attract, retain and motivate qualified personnel; the possibility of system failures or security breaches; risks relating to intellectual property and significant costs as a result of operating as a public company. These and other important factors discussed under the caption Risk Factors in our Quarterly Report on Form 10-Q for the quarterly period endedJune 30, 2020and our other filings with theSECcould cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent managements estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

*ALT Grades based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5 **P<0.004; Post-hoc comparison of Cohort 1 vs Cohorts 2&3 using repeated measures MANOVA/regression analysis ***U.S. and EU PKU treatment guidelines described in: Vockley J et al. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genetics in Medicine 2014;16: 188-200. van Spronsen FJ et al. Key European guidelines for the diagnosis and management of patients with phenylketonuria. Lancet Diabetes Endocrinol 2017; 5: 74356. ****P<0.05; Post-hoc comparison of Patients 3&6 vs Patients 4&5 using repeated measures MANOVA/regression analysis

Company Contacts Theresa McNeely Chief Communications Officer and Patient Advocate tmcneely@homologymedicines.com 781-301-7277

Media Contact: Cara Mayfield Senior Director, Patient Advocacy and Corporate Communications cmayfield@homologymedicines.com 781-691-3510

Read the original here:
Homology Medicines Announces Presentation of Positive Data from the Dose-Escalation Phase of the pheNIX Gene Therapy Trial for Adults with PKU -...

Magnetic Resonance Imaging Market Growth Estimation, Future Insights, Applications, Key Players, Size Analysis, COVID-19 Impact and MRI Industry…

By adminNovember 12, 2020Gene Therapy Clinics

Magnetic Resonance Imaging (MRI) Market Trends, Growth and Size Analysis By Type (Open MRI and Close MRI), Field Strength (High-Field MRI Systems), Disease Application (Brain and Neurological MRI), and End-Users (Hospitals & Clinics) Global Forecast Till 2023

Magnetic Resonance Imaging (MRI) Market Overview

Global magnetic resonance imaging market size valuation is expected to reach USD 5 Billion by 2023. The market would register a 3.5% CAGR during the assessment period (2018 to 2023), states MRFR in its recent MRI market research report.

The magnetic resonance imaging (MRI) market is growing pervasively and attributes to the increasing use of MRI systems to diagnose a myriad of diseases and disorders. Due to its various advantages, magnetic resonance imaging systems surpass the radiology imaging systems in terms of the adoption. Technological advances in molecular imaging and the growing demand for non-invasive diagnostic techniques positively impact MRI market growth.

The report defines all significant market aspects with experts opinions on current and historical data. The report also covers market statistics, investment opportunities, gross margins, competitive analysis, top business strategies, and a comprehensive assessment of the COVID 19 impacts on market growth. Moreover, increasing funding support for the development of MRI techniques escalates the market growth to furthered height. The market is estimated to witness several FDA approved launches of innovative products and approaches, which would multiply Magnetic Resonance Imaging Market share.

Request Free Sample Copy at: https://www.marketresearchfuture.com/sample_request/6194

Rising technological advancements are estimated to propel the growth of the market. The growing prevalence of myriads of chronic diseases and increasing awareness about the innovative diagnostics methods influence the growth of the market. Additional factors, such as high R & D investments made for developing efficient imaging solutions, foster the growth of the MRI market throughout the analysis period.

Conversely, stringent regulatory processes are projected to obstruct the growth of the market in the years to come. Also, high costs associated with MRI systems hamper market growth. Nevertheless, rising financial support programs would support the growth of the market throughout the predicted period, suiting to changing needs of healthcare professionals.

Global Magnetic Resonance Imaging Market Segmentation

By Type, the global magnetic resonance imaging market is segmented into Open MRI, Closed MRI, Standard Bore MRI, wide-bore MRI.

By Field Strength, the global magnetic resonance imaging market High-Field MRI Systems, 1.5t MRI Systems, 3t MRI Systems, Low-To-Mid-Field MRI Systems, Very-High-Field MRI Systems, and others.

By Disease Application, the global magnetic resonance imaging market Spine & Musculoskeletal MRI, Brain & Neurological MRI, Pelvic & Abdominal MRI, Breast MRI, Cardiovascular MRI, and others.

By End-Users, the global magnetic resonance imaging market Diagnostic Imaging Centers, Hospitals & Clinics, Research Laboratories, Pharmaceutical & Biotechnology Companies, and others.

Magnetic Resonance Imaging Market Regional Outlook

North America dominates the global magnetic resonance imaging (MRI) market. The largest MRI market share attributes to the strong presence of several industry players and technological advancements in molecular imaging. Besides, factors such as the increasing market demand for non-invasive imaging techniques and increasing funding foster regional market growth.

Additionally, well-established healthcare sectors in the region, alongside the rising healthcare spending and adoption of MRI systems in medical diagnostics, spur the diagnostic imaging services market growth. The US and Canada account for major shares in the North American MRI market.

Europe stands second in the global magnetic resonance imaging (MRI) market. The market growth is driven by the increasing funding to support preclinical researches from regulatory authorities in the diagnosis of various chronic diseases. Moreover, augmenting demand for innovative & easy to use imaging agents in the medical sector has been increasing the cardiac MRI market size. Furthermore, growing healthcare expenses, the resurging economy in the region, and spreading awareness about MRI systems modalities positively impact the regional market.

The Asia Pacific magnetic resonance imaging (MRI) market is growing rapidly. Factors such as rising numbers of biotechnology and pharmaceutical companies increase the size of the MRI market excellently. Besides, the growing penetration of imaging technology in the healthcare sector for medical imaging purposes fosters regional market growth.

MRI market Competitive Analysis

Highly competitive, the MRI market appears fragmented due to the presence of several notable players. To gain a larger competitive share in the market, players adopt strategies such as mergers & acquisitions, collaboration, expansion, and product & technology launch. Industry players make substantial investments to drive R&D and expansion plans. R & D investments help them better their imaging agents, and expansion investment helps them increase their global footprints.

Major Players:

Players leading the global Magnetic Resonance Imaging Market include Hitachi, Siemens AG, Canon Medical Systems, GE Healthcare, Philips, Toshiba Corporation, Toshiba Corporation, Xingaoyi, and Aurora Imaging Technologies, Inc., among others.

Browse Detailed TOC with COVID-19 Impact Analysis at: https://www.marketresearchfuture.com/reports/magnetic-resonance-imaging-market-6194

Industry/Innovation/Related News:

Axonics Modulation Technologies, Inc.(the US), a medical technology company, announced receiving the US FDA premarket approval supplement approval for its 3T full-body MRI conditional labeling Axonics r-SNM System. Axonics SNM devices are designed for the treatment of urinary and bowel dysfunction. This FDA approval allows Axonics to provide healthcare professionals with more choices in selecting the optimal MR scanner for their patients imaging needs.

FDA approved the Axonics r-SNM System with full-body conditional labeling for 1.5T MRI scanners. With this incremental approval for 3T scans, the Axonics device continues to be the only SNM system available in the US that is MRI compatible for both 1.5T and 3T full-body scans.

Browse More Healthcare Related Research Report at:

Global Gene Therapy Market size was recorded at a value of USD 524 million in 2018 and is touted to register a CAGR of 40.7%.

chronic disease management market size to grow at a significant CAGR of 14.5% between 2019 and 2025

The Global Insulin Pump Market size is expected to reach a valuation of 8,520.9 million USD with exhibiting a CAGR of 8.4% from 2017 to 2023

NOTE: Our team of researchers are studying Covid19 and its impact on various industry verticals and wherever required we will be considering covid19 footprints for a better analysis of markets and industries. Cordially get in touch for more details.

About Market Research Future:

Contact:

Akash Anand

Market Research Future

+1 646 845 9312

Email: [emailprotected]

Choroideremia Treatment Market Share Analysis by Copernicus Therapeutics, Inc, Wize Pharma Inc, Spark Therapeutics, Inc – Sunrise Nigeria

By adminNovember 12, 2020Gene Therapy Clinics

Data Bridge Market Researchhas added an exhaustive research study of theGlobal Choroideremia Treatment Marketdetailing every single market driver and intricately analyzing the business vertical. The research report has abilities to raise as the most significant market worldwide as it has remained playing a remarkable role in establishing progressive impacts on the universal economy. The research report presents a complete assessment of the market and contains a future trend, current growth factors, attentive opinions, facts, and industry validated market data.

Global Choroideremia Treatment Marketis expected to grow at a steady CAGR in the forecast period of 2019-2026.Increase in strategic alliances between the pharmaceuticals companies and high demand of disease specific novel therapies are the key factors that fueling the market growth. Global Choroideremia Treatment Market By Treatment Type (Gene Therapy, Surgery), Route of Administration (Oral, Injectable), End- Users (Hospitals, Homecare, Specialty Clinics, Ophthalmic Clinics and Others), Distribution Channel (Hospital Pharmacies, Retail Pharmacies), Geography (North America, South America, Europe, Asia-Pacific, Middle East and Africa) Forecast to 2026

Download exclusive PDF sample report @https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-choroideremia-treatment-market

Key Developments in the Market:

Reasons to Purchase this Report

Order a Copy of Global Choroideremia Treatment Market Report @https://www.databridgemarketresearch.com/inquire-before-buying/?dbmr=global-choroideremia-treatment-market

Some of the major competitors currently working in the global choroideremia treatment market areBiogen, 4D Molecular Therapeutics, Copernicus Therapeutics, Inc, Wize Pharma Inc, Spark Therapeutics, Inc, PIXIUM VISION, Retina Implant AG, F. Hoffmann-La Roche Ltd and others.

Market Definition:

Choroideremia is also known as choroidal sclerosis is a rare, degenerative, X-linked inherited retinal disorder characterized by progressive degeneration of the choroid, retinal pigment epithelium (RPE) and retina due to Mutations in the CHM gene. This CHM gene required to produce Rab escort protein-1 (REP-1). The condition gets its name from the distinctive sweet odor of affected infants urine and is also c, a protein that takes part in targeting vesicles (small sacs of substances) into, out of, and within cells.

According to the statistics published by U.S. Department of Health & Human Services, an estimated population of choroideremia is about 1 in 50,000-100,000 people. Presence of refined healthcare infrastructure and emerging new market are the key factors for growth of this market.

Market Drivers

Market Restraints

Segmentation:Global Choroideremia Treatment Market

By Treatment

By Route of Administration

By End Users

By Distribution Channel

ByGeography

Download Detailed TOC @https://www.databridgemarketresearch.com/toc/?dbmr=global-choroideremia-treatment-market

Read the original post:
Choroideremia Treatment Market Share Analysis by Copernicus Therapeutics, Inc, Wize Pharma Inc, Spark Therapeutics, Inc - Sunrise Nigeria

Fight for the rights of unborn – The Daily Telegram

By adminNovember 11, 2020Stem Cell Doctors

Tuesday Nov10,2020at9:00AM

The Roe v. Wade ruling set America on a destructive path to devaluing life. Death clinics have been set up across this nation to murder children who have no choice. Doctors actually make money practicing this.

Instead of saving lives, as many believe doctors take an oath to do, they are taking life away. The most abhorrent of this practice is partial birth abortion, where a child, moments from taking its first breath, is pulled from the womb feet first and has his/her skull pierced before seeing the light of day. What kind of culture accepts this type of practice?

Some in the medical profession rationalize abortion and embryonic stem cell research as healthy for humanity. Healthy for what kind of humanity? There are those doctors who have found adult stem cell use much more effective and they are less susceptible to disease. Isnt it strange how this research doesnt seem to be able to get much acknowledgment from the "unbiased" national media?

Sarah Palins Downs-Syndrome child could have ended up in some clinics dumpster had she given into the "culture of death." She chose life and with it the rewards of motherhood of a special needs child. The Democratic party promotes the destructive path of devaluing life. (They even cheer with a standing ovation. See New York House Jan. 22, 2020). Do you think the current candidates would choose life had it been found out prior to birth that their child was going to be "defective"?

Yes, this culture can be reversed by continuing to fight (NEVER GIVE UP) and by voting for those that would fight for the "rights" of the unborn!

As to economic ruin on a grand scale, as referred to by some if we continue on the current path: We still live in the most prosperous nation in the world as shown by the amount of people from other nations that still try and get here. When we as a nation put financial prosperity ahead of life, the following verse rings true. "People who want to get rich fall into temptation and a trap and into many foolish and harmful desires that plunge men into ruin and destruction. For the love of money is a root for all sorts of evil."

Steven Wilson

Blissfield

Read this article:
Fight for the rights of unborn - The Daily Telegram

Genetic Mechanism Identified in Neonatal Diabetes Could Offer Insights into Other Forms of the Disease – Genetic Engineering & Biotechnology News

By adminNovember 11, 2020Stem Cell Doctors

New insights into the genetic basis of a rare type of diabetes in babies have uncovered a biological pathway that is fundamental to insulin production by pancreatic cells, and which could boost research into new treatments for more common forms of diabetes. An international research team led by scientists at the University of Exeter, the Universit Libre de Bruxelles, and the University of Helsinki, used genome sequencing to reveal that a group of babies with shared clinical features, including the development of diabetes soon after birth, all had genetic changes in the YIPF5 gene, which is involved in cell trafficking from the endoplasmic reticulum (ER) to the Golgi. The team then combined stem cell research and CRISPR gene editing to show that this gene is essential for the function of the cells that produce insulin.

The research demonstrated how the genetic changes result in high levels of stress within the cells, causing cell death, and also showed, for the first time, that YIPF5 gene function is essential for neurons and insulin-producing cells, but appears to be dispensable for the function of other cells.

Co-study lead, Elisa De Franco, PhD, from the University of Exeter, said, This study highlights the importance of gene discovery to further our understanding of fundamental mechanisms in biology. In this case, our research has resulted in the identification of a gene essential for both insulin-producing cells and neurons, highlighting a biological pathway we previously did not know was so fundamental for insulin-producing cells. This has the potential to open new avenues of research and ultimately result in a better understanding of how other types of diabetes develop.

De Franco and colleagues reported on their findings in the Journal of Clinical Investigation (JCI), in a paper titled, YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress.

Neonatal diabetes develops before the age of six months, and is caused by reduced numbers of insulin-producing pancreatic cells, or impaired cell function, the authors explained. Previous research has found that neonatal diabetes is most likely caused by a mutation in a single gene, rather than presenting as an autoimmune type 1 form of the disease. To date, 30 genetic causes have been described, which account for 82% of cases, the team noted. Many patients with neonatal diabetes also have neurological symptoms, which is not surprising, the researchers continued, as cells and neurons have many genes and cellular functions in common. Pathogenic variants in 11 genes are already known to cause neonatal diabetes with neurological features, and one of the pathways known to be crucial for the function of both cells and brain cells is the endoplasmic reticulum stress response. In fact, Pathogenic variants in eight genes known to be involved in regulating the ER stress response have been found to caused diabetes (ranging from neonatal to adolescent/adult-onset diabetes), often associated with neurological features, the scientists pointed out.

To further study which genes are key to the function of insulin-producing cells, in the context of neonatal diabetes, the research team studied the genetics of almost 190 patients from all over the world who developed diabetes soon after birth. Identifying the genes causing syndromic forms of neonatal diabetes that include neurological features can highlight pathways important for development and function of -cells and neurons, giving insights into the pathogenesis of more common diseases, they noted. The results identified six babies who had neonatal diabetes and other very similar clinical featuresincluding epilepsy and microcephalyand who all exhibited mutations in the YIPF5 gene.

Researchers at the Universit Libre de Bruxelles and the University of Helsinki then carried out a series of studies in insulin-producing cells and in stem cells to try to understand the function of YIPF5 in the insulin-producing cells. We used three human cell models (YIPF5 silencing in EndoC-H1 cells, YIPF5 knockout and mutation knockin in embryonic stem cells, and patient-derived induced pluripotent stem cells) to investigate the mechanism through which YIPF5 loss of function affects cells, the investigators explained. Their results showed that when the gene was lacking, or had the same mutations as those found in the neonatal diabetes patients, the insulin-producing cells couldnt function normally to produce enough insulin. And an attempt to cope with this malfunction the cells activated stress mechanisms, which ultimately resulted in cell death. YIPF5 deficiency reduces -cell survival by enhancing the ER stress response and sensitizing human -cells to ER stress-induced apoptosis, they commented.

Co-senior study author Timo Otonkoski, from the University of Helsinki, explained, Using the CRISPR gene scissor DNA-editing technology we could correct the patient mutation in stem cells in order to fully understand its effects. The combination of gene editing with stem cells provides powerful new tools for the study of disease mechanisms. Colleague and co-senior author, Miriam Cnop, PhD, from the Universit Libre de Bruxelles, continued, The possibility to generate insulin-producing cells from stem cells has given us the possibility to study what goes wrong in cells from patients with this rare form and also other types of diabetes. It is an extraordinary disease-in-a-dish model to study mechanisms of disease and test treatments.

The teams study results offer new insights into which cellular steps are important for making insulin, and for maintaining the function of insulin-producing cells in the pancreas. This insight could help researchers develop better therapies to treat patients with common types of diabetes that affect 460 million people worldwide.

To the best of our knowledge, this is the first report of mutations in a gene affecting ER-to-Golgi trafficking resulting in diabetes by increasing -cell ER stress, uncovering a critical role of YIPF5 in the human -cell, the authors reported. Our findings highlight a biological pathway essential for -cells.

We are very grateful to the patients, their families, and their doctors for their participation in the study, noted Andrew Hattersley, PhD, one of the senior authors of the study, from the University of Exeter. Without them, we could not have accomplished this. It is our wish that further research will benefit the patients, to facilitate diagnosis and treatment of their diabetes.

Anna Morris, assistant director of research strategy and partnerships at Diabetes UK, which provided funding for the studies, said, These findings provide important new information on how beta cells in the body manufacture insulin and what happens when this process goes wrong. Understanding more about how rarer forms of diabetes develop brings us closer to discovering new ways to cure and prevent all forms of the condition. This is a key part of Diabetes UKs new strategy, and we are proud to have funded De Francos vital research.

Continue reading here:
Genetic Mechanism Identified in Neonatal Diabetes Could Offer Insights into Other Forms of the Disease - Genetic Engineering & Biotechnology News

Doctors Debate: Is Intensive or Low-Intensity Chemotherapy Plus BCR-ABL TKI Therapy Best for Treatment of Ph+ ALL? – Targeted Oncology

By adminNovember 11, 2020Stem Cell Doctors

Philadelphia chromosomepositive acute lymphoblastic leukemia (Ph+ ALL) can be treated using either intensive chemotherapy with a BCR-ABL tyrosine kinase inhibitor (TKI) or nonintensive chemotherapy. Which strategy to employ is an ongoing clinical question that affects patients from the front-line to third-line settings.

During the Society of Hematologic Oncology Virtual Annual Meeting, Nicholas J. Short, MD, an assistant professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center in Houston, argued that intensive chemotherapy combined with a BCR-ABL TKI still holds the place of standard-of-care treatment for Ph+ ALL. Sabina Chiaretti, MD, PhD, a researcher in the Department of Translational and Precision Medicine at Sapienza University in Rome, Italy, made the case that less is more, arguing for a targeted approach to managing Ph+ ALL.1,2

Perhaps the best reason to use the standard-of-care strategy for treating patients with Ph+ ALL is that it is known to improve survival in the front-line setting and has demonstrated increased molecular responses and survival in the second- and third-line settings, Short explained in his presentation. When complete molecular responses (CMRs) are observed with a therapy, Short says, it increases the chance of cure in patients.1

The best opportunity to cure someone with newly diagnosed acute leukemia of any type, and in particular, Philadelphia chromosomepositive ALL, is in the frontline setting. It is therefore very important that you choose the frontline regimen appropriately. This an important debate because of the emerging data with lower-intensity regimens that have brought on some desire to treat patients with less chemotherapy, Short told Targeted Therapies in Oncology (TTO) in an interview.

Understanding How Patients Benefit

Prior to 2016, the impact of CMRs on patients with Ph+ ALL had not yet been defined. Findings from a study conducted by Short and colleagues showed that achieving a CMR at 3 months can potentially identify which patients will have long-term overall survival (OS) and relapse-free survival (RFS) on intensive chemotherapy without stem cell transplant (SCT) compared with those who have lower CMRs at 3 months.3

The study enrolled 202 patients with Ph+ ALL to receive the frontline intensive chemotherapy combination of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD). At 3 months, the OS was 127 months for patients who had higher CMRs compared with 38 months among those with lower CMRs (HR, 0.42; 95% CI, 0.21-0.82;P =.0). Also, at 3 months, the RFS among the higher-CMR population was 26 months versus 18 months for the lower-CMR population (HR, 0.43; 95% CI, 0.21-0.78;P =.01).

Overall, the findings showed that higher CMRs resulted in superior survival, whereas lower CMRs left patients with poor outcomes.

This research laid the groundwork for an understanding of how patients benefit from and which patients have the best responses to intensive chemotherapy.

Patient Outcomes With Intensive Chemotherapy Plus a BCR-ABL TKI

Short previously presented long-term safety and efficacy results from the combination of hyper-CVAD and the third-generation BCR-ABL inhibitor ponatinib (Iclusig) at the 2019 American Society of Hematology (ASH) Annual Meeting. Patients with newly diagnosed Ph+ ALL had sustained responses on this treatment without hematopoietic SCT (HSCT), demonstrating its potential for cure, Short noted.

The best outcomes that have been reported so far in the literature have been with the combination of intensive chemotherapy with hyper-CVAD plus ponatinib. For the study, we have long-term outcomes data available. Theres a 5-year overall survival rate of 74%, which is better than we see with other tyrosine kinase inhibitors and also better than what we weve seen to date with lower-intensity regimens, Short said.

This is likely driven by the higher rate of complete molecular response that we see with the combination of intensive chemotherapy plus ponatinib, he added.

Of the 68 patients evaluated, at a median follow-up of 43 months (range, 2-92), 71% were alive and still in remission at the time of data cutoff. After 3 years, the complete remission (CR) rate observed with the combination was 84%. Patients also achieved an event-free survival (EFS) rate of 70% and OS of 78% with hyper-CVAD plus ponatinib. It was estimated that the 5-year rates for CR, EFS, and OS would be 84%, 68%, and 73%, respectively.4

Notably, during this analysis, 11 patients relapsed after a median of 20 months in remission (range, 5-64 months). Three of the patients who relapsed were still receiving ponatinib, but 6 were being treated with another TKI, and 2 were not receiving any TKI. Among those who relapsed while receiving ponatinib, an ABL1 E255K kinase domain mutation was detected in 2 patients, which may have affected outcomes. The remaining patients who were treated with ponatinib but relapsed within 20 months did not have a tumor mutation.

It was also notable that a trend toward improved OS was observed in patients who did not undergo HSCT compared with those who did, according to a landmark analysis. Specifically, the OS rate for patients who did not undergo HSCT was 90% versus 66% for those who did (P=.07).

The safety profile of hyper-CVAD combined with ponatinib was tolerable in the newly diagnosed Ph+ ALL study population. The majority of adverse events (AEs) observed with the combination were grade 1 and 2 in severity. Still, dose reductions were necessary in 37% of patients as a results of AEs. The most common events that occurred were rash (n=7), liver function test abnormalities (n=5), pancreatitis (n=3), deep vein thrombosis (n = 2), and thrombocytopenia (n=2). There were 9 deaths in the study of patients who were in CR. Also, 2 ponatinib-related deaths occurred, leading to a protocol amendment regarding the dose level of the drug. After the amendment, no additional patients died.

Similar efficacy and safety were observed in earlier studies of hyper-CVAD plus a BCR-ABL TKI. First, results of the 2015 study of hyper-CVAD in combination with imatinib (Gleevac; NCT00038610) showed a 93% CR rate in the 45 patients with active disease at the time of enrollment. Additionally, at 5 years, the OS rate with hyper-CVAD plus imatinib was 43%.5

Satisfactory outcomes were reported with the intensive chemotherapy and BCR-ABL TKI combination of frontline hyper-CVAD and dasatinib (Sprycel) in patients with Ph+ ALL. Long-term follow-up results from the phase 2 study were published in the journal Cancer. The investigators concluded that the combination is able to achieve long-term remission in patients. In the 72 patients evaluated, the CR rate was 96% and the 5-year OS rate was 46%.6

Based on these 2015 data from 2 combinations, the 2019 data presented at ASH confirm the benefit of intensive chemotherapy combined with BCR-ABL TKI therapy, noted Short; however, the study conclusion mentioned that other BCR-ABL TKIs, such as blinatumomab (Blincyto), still must be evaluated in the frontline setting of Ph+ ALL.1,4

Is There a Role for Low-Intensity Chemotherapy?

To further support his argument around intensive chemotherapy plus TKI therapy, Short reviewed the emerging data of lower-intensity chemotherapy regimens. His overarching point was that the trials are too preliminary to change the current standard of care.

While I agree that lower-intensity therapies need to be evaluated, my argument is that those are not yet standard of care. There are not enough long-term data for those studies that show promise for treating patients with low-intensity chemotherapy outside of clinical trials, Short stated during the interview.

Short examined data from the 2007 study of imatinib plus chemotherapy in elderly patients with Ph+ ALL, which showed a superior CR rate compared with induction chemotherapy but did not show a survival benefit. The 1-year OS rate was 74%.7 In addition, the 2016 study of dasatinib with low-intensity chemotherapy in elderly patients, as well as the 2019 study of nilotinib (Tasigna) in patients with newly diagnosed Ph+ALL, demonstrated improved cure rates compared with induction therapy, but the OS was not satisfactory.8,9 Specifically, dasatinib plus low-intensity chemotherapy resulted in a 36% OS at 5 years, and nilotinib plus low-intensity chemotherapy led to a 2-year OS rate of 47%.

The most impressive survival results were observed with low-intensity chemotherapy plus ponatinib in elderly or unfit patients with Ph+ ALL treated in the phase 2 Gimema LAL1811 trial (NCT01641107). The combination led to a 2-year OS rate of 64%, which Short attributed to the higher CMR rate of 46%.10

After reviewing these data, Short maintained his argument that intensive chemotherapy combined with a BCR-ABL inhibitor is a proven frontline standard of care for Ph+ ALL. The only question that remains, Short told TTO, is whether the ability to skip transplant is an important accomplishment with the regimens.

Low-Intensity Chemotherapy as Ph+ ALL Treatment

Ph+ ALL is of the highest concern in patients 60 years and above. Perhaps due to the age of these patients, the satisfactory outcomes observed with intensive chemotherapy are often cancelled out by the overwhelming toxicity, Chiaretti explained during her presentation. Because of the toxicity of intensive chemotherapy, Chiaretti argues that long-term outcomes for this strategy are unsatisfactory, with ponatinib being the only exception.2

Today, we are lucky enough to be able to manage our patients with targeted therapies instead of chemotherapy. We should aim to use the best drugs that we have, which are TKIs and targeted therapies. The outstanding question is which are those patients who are at higher risk of relapse, so that we can use the best treatment for those patients, Chiaretti told TTO in an interview.

Success With Low-Intensity Chemotherapy and TKIs

In terms of low-intensity chemotherapy with a BCR-ABL TKI, the research around the GIMEMA strategy has shown high complete hematological response (CHR) rates, Chiaretti said, beginning with the study of imatinib in combination with steroids and without additional chemotherapy in elderly patients with Ph+ ALL (LAL0201-B; NCT00376467). Of the 30 participants aged 60 to 89 years, 29 were evaluable for response. The CHR rate achieved was 100%.11 Later, in the GIMEMA LAL1205 protocol study (NTC02744768), patients aged 18 to 84 with Ph+ ALL were treated with frontline dasatinib in combination with intrathecal chemotherapy and also achieved a 100% CHR rate.12

Chiaretti made note that all the GIMEMA protocols resulted in satisfactory CHR without additional chemotherapy, demonstrating that intensive chemotherapy may no longer be necessary for this patient population.

In the LAL0904 study (NCT00458848), a 96% CHR rate was observed in 49 evaluable patients. The regimen consisted of imatinib plus induction and consolidation chemotherapy in patients aged 16 to 60 years with Ph+ ALL. The treatment was deemed feasible for adult patients with Ph+ ALL based on this protocol.13 Similarly, 39 patients with Ph+ ALL 60 years and older in the LAL1408 study (NCT01025505) achieved a CHR rate of 94% on treatment with nilotinib in combination with imatinib. Investigators led by Giovanni Martinelli, MD, concluded that the results of this combination were not different from those observed with single-agent imatinib.14

For patients 60 years and older in the LAL1811 study, the CHR was 95% with ponatinib. This study confirmed the activity of ponatinib in this patient population.15

Finally, Chiaretti noted unpublished results from the LAL1509 trial (NCT01361438), which evaluated dasatinib total therapy in patients aged 18 to 60 . The CHR rate was reported as 97%.2 Notably, the safety profile of the drugs evaluated in all these GIMEMA studies were well tolerated.

Homing in on the difference in survival in patients treated with intensive chemotherapy versus de-intensified chemotherapy, intensive chemotherapy appeared to have better rates. Results of a 2012 study showed a 2-year event-free survival of 63% (95% CI, 39%-87%) with de-intensified chemotherapy in 29 patients with Ph+ ALL.16 In another study of 30 patients, low-intensity chemotherapy with imatinib led to a 5-year EFS rate of 32.1% compared with 42.2% with intensive chemotherapy. The 5-year OS rate in this study was 43% with low-intensity chemotherapy compared with 48.3% with intensive chemotherapy.17 Chiaretti noted, however, that the CT rate was not significantly different between these studies. Moreover, both responses and survival would be improved upon with a more target treatment approach, Chiaretti said.

Targeted Treatment of Ph+ ALL

Highlighting the results of the Gimema LAL2116 D-ALBA trial of front-line dasatinib in combination with blinatumomab as treatment of adults patients with Ph-ALL (NCT02744768), Chiaretti made the case of targeted therapy without addition of chemotherapy in this patient population.

The study of 63 evaluable patients at a median age of 54.50 years (range, 24.1-81.7 years) achieved a CMR rate of 60.4% (95% CI, 46%-73.5%), meeting the studys primary end point. Median follow-up was 14.3 months (range, 0.9-25), and the OS rate observed with the amount of follow-up was 95.2% (95% CI; 90.1%-100%). The disease-free survival rate was 89.7% (95% CI, 82.2%-97.9%).18

In terms of safety, 148 AEs were observed, and 41 serious AEs were observed. The most common AEs included infections and infestations, general disorders, and gastrointestinal disorders.

The key takeaway from Chiarettis presentation was that although low-intensity chemotherapy with a TKI is less toxic than intensive chemotherapy, ultimately, patients would have better overall outcomes with chemotherapy removed from the course of treatment: We dont want patients to succumb to their disease. If we use chemotherapy, the risk of treatment-related morality is very high.

Chiaretti concluded that a chemotherapy therapy-free induction and consolidation approach may be best for patients with Ph+ ALL.

References:

1. Short N. Is less more? intensive vs non-intensive approach to adults with Ph+ALL: intensive approach. Presented at: 2020 Society of Hematologic Oncology Annual Meeting; September 9-12, 2020; virtual.

2. Chiaretti S. Is less more: intensive vs nonintensive approach to adults with Ph+ ALL: non-intensive approach. Presented at: 2020 Society of Hematologic Oncology Annual Meeting; September 9-12, 2020; virtual.

3. Short N, Jabbour E, Sasaki K, et al. Impact of complete molecular response on survival in patients with Philadelphia chromosomepositive acute lymphoblastic leukemia. Blood. 2016;128(4):504-507. doi:10.1182/blood-2016-03-707562

4. Short NJ, Kantarjian HM, Ravandi F, et al. Long-term safety and efficacy of hyper-CVAD plus ponatinib as frontline therapy for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2019;134 (suppl 1):283. doi:10.1182/blood-2019-125146

5. Daver N, Thomas D, Ravandi F, et al. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica. 2015;100(5):653-661. doi:10.3324/haematol.2014.118588

6. Ravandi F, OBrien SM, Cortes J, et al. Long-term follow-up of phase II study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015;121(23):4158-4164. doi:10.1002/cncr.29646

7. Ottmann OG, Wassmann B, Pfeifer H, et al; GMALL Study Group. Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Cancer. 2007;109(10):2068-2076. doi:10.1002/cncr.22631

8. Ottmann OG, Pfeifer H, Cayuela JM, et al. Nilotinib (Tasigna) and low intensity chemotherapy for first-line treatment of elderly patients withBCR-ABL1-positive acute lymphoblastic leukemia: final results of a prospective multicenter trial (EWALL-PH02). Blood. 2018;132(suppl 1):31. doi:10.1182/blood-2018-99-114552

9. Liu B, Wang Y, Zhou C, et al. Nilotinib combined with multi-agent chemotherapy in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-center prospective study with long-term follow-up. Ann Hematol. 2019;98(3):633-645.doi:10.1007/s00277-019-03594-1

10. Martnelli G, Piciocchi A, Papayanndis C, et al. First report of the GIMEMA LAL1811 phase II prospective study of the combination of steroids with ponatinib as frontline therapy of elderly or unfit patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood.2017;130 (suppl 1):99.

11. Vignetti M, Fazi P, Camino G, et al. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosomepositive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dellAdulto (GIMEMA) LAL0201-B protocol. Blood. 2007;109(9):3676-3678. doi:10.1182/blood-2006-10-052746

12. Fo R, Vitale A, Vignetti M, et al; MIMEMA Acute Leukemia Working Party. Dasatinib as first-line treatment for adult patients with Philadelphia chromosomepositive acute lymphoblastic leukemia. Blood.2011;118 (25):6521-6528. doi:10.1182/blood-2011-05-351403

13. Chiaretti S, Vitale A, Vignetti M, et al. A sequential approach with imatinib, chemotherapy and transplant for adult Ph+ acute lymphoblastic leukemia: final results of the GIMEMA LAL 0904 study. Haematologica. 2016;101(12):1544-1552. doi: 10.3324/haematol.2016.14453

14. Martinelli G, Papyannidis C, Piciocchi A, et al. Extremely high rate of complete hematological response of elderly Ph+ acute lymphoblastic leukemia (ALL) patients by innovative sequential use of nilotinib and imatinib. a GIMEMA protocol LAL 1408. Presented at: American Association for Cancer Research Annual Meeting 2014; April 5-9, 2014; San Diego, CA. Abstract 5552.

15. Papayannidis C, De Benedittis C, Soverini S, et al. Ponatinib is well tolerated and active in patients with relapsed/refractory Philadelphia positive acute lymphoblastic leukemia (PH+ ALL) and advanced phase of chronic myelogenous leukemia (DML) harbouring T315i mutation: the Bologna experience. Blood. 2013;122(21):3911. doi:10.1182/blood.V122.21.3911.3911

16. Ribera JM, Garca J, Fernndez-Abelln P, et al; PEHEMA Group. Lack of negative impact of Philadelphia chromosome in older patients with acute lymphoblastic leukaemia in the thyrosine kinase inhibitor era: comparison of two prospective parallel protocols. Br J Haematol. 2012;159(4):485-488. doi:10.1111/bjh.12043

17. Chalandon Y, Thomas X, Hayette S, et al; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. Blood. 2015;125(24);3711-3719. doi:10.1182/blood-2015-02-627935

18. Chiaretti S, Bassan R, Vitale A, et al. A Dasatinib-blinatumomab combination for the front-line treatment of adult Ph+ all patients. preliminary results of the GIMEMA LAL2116 D-ALBA trial; on behalf of GIMEMA Acute Leukemia Working Party. Presented at: European Hematology Association 2019 Annual Meeting; June 13-16, 2019; Amsterdam, the Netherlands. Abstract S1617.

Originally posted here:
Doctors Debate: Is Intensive or Low-Intensity Chemotherapy Plus BCR-ABL TKI Therapy Best for Treatment of Ph+ ALL? - Targeted Oncology