FDA Approves Genentech’s Tecentriq as Adjuvant Treatment for Certain People With Early Non-Small Cell Lung Cancer – Business Wire

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has approved Tecentriq (atezolizumab) as adjuvant treatment following surgery and platinum-based chemotherapy for adults with Stage II-IIIA non-small cell lung cancer (NSCLC) whose tumors express PD-L11%, as determined by an FDA-approved test.

Tecentriq is now the first and only cancer immunotherapy available for adjuvant treatment of NSCLC, introducing a new era where people diagnosed with early lung cancer may have the opportunity to receive immunotherapy to increase their chances for cure, said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. Todays landmark approval gives physicians and patients a new way to treat early lung cancer that has the potential to significantly reduce risk of cancer recurrence, after more than a decade with limited treatment advances in this setting.

Too many patients with early-stage lung cancer experience disease recurrence following surgery. Now, the availability of immunotherapy following surgery and chemotherapy offers many patients new hope and a powerful new tool to reduce their risk of cancer relapse, said Bonnie Addario, Co-founder and Chair, GO2 Foundation for Lung Cancer. With this approval, it is more important than ever to screen for lung cancer early and test for PD-L1 at diagnosis to help bring this advance to the people who can benefit.

The approval is based on results from an interim analysis of the Phase III IMpower010 study that showed treatment with Tecentriq following surgery and platinum-based chemotherapy reduced the risk of disease recurrence or death by 34% (hazard ratio [HR]=0.66, 95% CI: 0.50-0.88) in people with Stage II-IIIA (UICC/AJCC 7th edition) NSCLC whose tumors express PD-L11%, compared with best supportive care (BSC). Safety data for Tecentriq were consistent with its known safety profile and no new safety signals were identified. Fatal and serious adverse reactions occurred in 1.8% and 18%, respectively, of patients receiving Tecentriq. The most frequent serious adverse reactions (>1%) were pneumonia (1.8%), pneumonitis (1.6%), and pyrexia (1.2%).

The review of this application was conducted under the FDAs Project Orbis initiative, which provides a framework for concurrent submission and review of oncology medicines among international partners. According to the FDA, collaboration among international regulators may allow patients with cancer to receive earlier access to products in other countries where there may be significant delays in regulatory submissions. Simultaneous applications were submitted to regulators in the United States, Switzerland, the United Kingdom, Canada, Brazil and Australia under Project Orbis. Additionally, the FDA reviewed and approved the supplemental application under its Real-Time Oncology Review pilot program, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.

Tecentriq has previously shown clinically meaningful benefit in various types of lung cancer, with six currently approved indications in the U.S. In addition to becoming the first approved cancer immunotherapy for adjuvant NSCLC, Tecentriq was also the first approved cancer immunotherapy for front-line treatment of adults with extensive-stage small cell lung cancer (SCLC) in combination with carboplatin and etoposide (chemotherapy). Tecentriq also has four approved indications in advanced NSCLC as either a single agent or in combination with targeted therapies and/or chemotherapies. Tecentriq is available in three dosing options, providing the flexibility to choose administration every two, three or four weeks.

Genentech has an extensive development program for Tecentriq, including multiple ongoing and planned Phase III studies across different lung, genitourinary, skin, breast, gastrointestinal, gynecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines, as well as studies in metastatic, adjuvant and neoadjuvant settings across various tumor types.

About the IMpower010 study

IMpower010 is a Phase III, global, multicenter, open-label, randomized study evaluating the efficacy and safety of Tecentriq compared with BSC, in participants with Stage IB-IIIA NSCLC (UICC/AJCC 7th edition), following surgical resection and up to 4 cycles of adjuvant cisplatin-based chemotherapy. The study randomized 1,005 people with a ratio of 1:1 to receive either Tecentriq for 1 year (16 cycles), unless disease recurrence or unacceptable toxicity occurred, or BSC. The primary endpoint is investigator-determined DFS in the PD-L1-positive Stage II-IIIA, all randomized Stage II-IIIA and intent-to-treat (ITT) Stage IB-IIIA populations. Key secondary endpoints include overall survival (OS) in the overall study population, ITT Stage IB-IIIA NSCLC.

About lung cancer

According to the American Cancer Society, it is estimated that more than 235,000 Americans will be diagnosed with lung cancer in 2021. NSCLC accounts for 80-85% of all lung cancers and approximately 50% of patients diagnosed with NSCLC are diagnosed with early-stage (Stages I and II) or locally advanced (Stage III) disease. Today, about half of all people with early lung cancer still experience a cancer recurrence following surgery. Treating lung cancer early, before it has spread, may help prevent the disease from returning and provide people with the best opportunity for a cure.

About Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

Tecentriq U.S. Indications

Tecentriq is a prescription medicine used to treat adults with:

A type of lung cancer called non-small cell lung cancer (NSCLC).

A type of lung cancer called small cell lung cancer (SCLC).

It is not known if Tecentriq is safe and effective in children.

Important Safety Information

What is the most important information about Tecentriq?

Tecentriq can cause the immune system to attack normal organs and tissues in any area of the body and can affect the way they work. These problems can sometimes become severe or life threatening and can lead to death. Patients can have more than one of these problems at the same time. These problems may happen anytime during their treatment or even after their treatment has ended.

Patients should call or see their healthcare provider right away if they develop any new or worse signs or symptoms, including:

Lung problems

Intestinal problems

Liver problems

Hormone gland problems

Kidney problems

Skin problems

Problems can also happen in other organs.

These are not all of the signs and symptoms of immune system problems that can happen with Tecentriq. Patients should call or see their healthcare provider right away for any new or worse signs or symptoms, including:

Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include:

Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if patients undergo transplantation either before or after being treated with Tecentriq. A healthcare provider will monitor for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider will check patients for these problems during their treatment with Tecentriq. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may also need to delay or completely stop treatment with Tecentriq if patients have severe side effects.

Before receiving Tecentriq, patients should tell their healthcare provider about all of their medical conditions, including if they:

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq when used alone include:

The most common side effects of Tecentriq when used in lung cancer with other anti-cancer medicines include:

Tecentriq may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of Tecentriq. Patients should ask their healthcare provider or pharmacist for more information about the benefits and side effects of Tecentriq.

Report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.

Report side effects to Genentech at 1-888-835-2555.

Please see http://www.Tecentriq.com for full Prescribing Information and additional Important Safety Information.

About Genentech in cancer immunotherapy

Genentech has been developing medicines to redefine treatment in oncology for more than 35 years, and today, realizing the full potential of cancer immunotherapy is a major area of focus. With more than 20 immunotherapy molecules in development, Genentech is investigating the potential benefits of immunotherapy alone, and in combination with various chemotherapies, targeted therapies and other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system.

In addition to Genentechs approved PD-L1 checkpoint inhibitor, the companys broad cancer immunotherapy pipeline includes other checkpoint inhibitors, individualized neoantigen therapies and T cell bispecific antibodies. For more information visit http://www.gene.com/cancer-immunotherapy.

About Genentech in lung cancer

Lung cancer is a major area of focus and investment for Genentech, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have five approved medicines to treat certain kinds of lung cancer and more than 10 medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

Read the original here:
FDA Approves Genentech's Tecentriq as Adjuvant Treatment for Certain People With Early Non-Small Cell Lung Cancer - Business Wire

Worldwide Cell Therapy Consumables Industry to 2031 – Featuring Bio-Techne, Irvine Scientific and Sartorius Among Others – PRNewswire

DUBLIN, Oct. 12, 2021 /PRNewswire/ -- The "Cell Therapy Consumables Market by Type of Consumable, Type of Cell Therapy, Scale of Operation, Type of End-User and Key Geographical Regions: Industry Trends and Global Forecasts, 2021 - 2031" report has been added to ResearchAndMarkets.com's offering.

This report features an extensive study on the consumable providers within the cell therapy industry. The study also includes an elaborate discussion on the future potential of this evolving market.

According to the US Food and Drug Administration (FDA), there has been an evident increase in the number of cell and gene therapy products being evaluated in early phases of development. This can further be validated by the observed upsurge in the number of investigational new drug (IND) applications. In fact, more than 800 IND applications have been filed for ongoing clinical studies, indicating remarkable scientific progress and therapeutic promise of these breakthrough drug candidates. However, manufacturing of cell therapies is a complex and capital-intensive process fraught with a wide range of challenges. Some of the key concerns of contemporary innovators include raw material supply constraints, current facility limitations, high cost of ancillary materials (buffers, growth factors and media) used in upstream processes, regulatory and compliance-related issues, and inconsistencies related to quality attributes of the final product. Further, the onset of recent COVID-19 pandemic has created additional challenges for therapy developers, in terms of procuring the required raw materials, by disrupting well-established supply chains.

Recent reports indicate that the global demand for human serum albumin (a key component of cell culture media for use in a multitude of therapeutic and emerging biotech areas) has increased at an annual rate of 10%-15%. On the contrary, the use of animal components is highly disregarded by the US FDA, European Medicines Agency (EMA), and other regulatory bodies on the grounds that they pose an undesirable risk of transmitting infectious agents, such as prions (mad cow disease) and virus (HIV), as well as enable high batch-to-batch variation. Consequently, serum-free and xeno-free media have proven to be a promising alternative to serum derived components. In order to produce quality cellular therapies, several drug developers prefer to rely on third-party service providers for the supply of raw materials, such as cell culture medium, cell isolation kits and cell separation reagents.

Presently, over 60 service providers are actively engaged in providing consumable/raw material products for the production of cell therapies. The current consolidated market landscape is primarily dominated by the presence of large players, capturing a substantial proportion of the market share. In the recent past, many of the aforementioned service providers have also forged strategic alliances and/or acquired other players, in order to further enhance their respective service offerings. Given that the demand for cell therapies is indubitably rising, the corresponding opportunity for cell therapy consumable service providers is expected to witness steady growth, over the next decade.

Amongst other elements, the report features:

Key Questions Answered

Key Topics Covered:

1. PREFACE

2. EXECUTIVE SUMMARY

3. INTRODUCTION

4. MARKET LANDSCAPE 4.1. Chapter Overview 4.2. Cell Therapy Kit Providers: List of Players 4.3. Cell Therapy Media Providers: List of Players 4.4. Cell Therapy Reagent Providers: List of Players 4.5. Analysis by Type of Consumable, Type of Cell Therapy and Application Area (Grid Representation)

5. COMPANY COMPETITIVENESS ANALYSIS 5.1. Chapter Overview 5.2. Key Assumptions and Parameters 5.3. Methodology 5.4. Company Competitiveness: Kit Providers 5.5. Company Competitiveness: Media Providers 5.6. Company Competitiveness: Reagent Providers

6. BRAND POSITIONING OF KEY INDUSTRY PLAYERS 6.1. Chapter Overview 6.2. Scope and Methodology 6.3. Bio-Techne 6.4. Miltenyi Biotec 6.5. Sartorius 6.6. STEMCELL Technologies 6.7. Thermo Fisher Scientific

7. COMPANY PROFILES 7.1. Chapter Overview 7.2. Miltenyi Biotec 7.2.1. Company Overview 7.2.2. Product Portfolio 7.2.3. Recent Developments and Future Outlook 7.3. STEMCELL Technologies 7.3.1. Company Overview 7.3.2. Product Portfolio 7.3.3. Recent Developments and Future Outlook 7.4. Bio-Techne 7.4.1. Company Overview 7.4.2. Product Portfolio 7.4.3. Recent Developments and Future Outlook 7.5. Irvine Scientific 7.5.1. Company Overview 7.5.2. Product Portfolio 7.5.3. Recent Developments and Future Outlook 7.6. Thermo Fisher Scientific 7.6.1. Company Overview 7.6.2. Product Portfolio 7.6.3. Recent Developments and Future Outlook 7.7. Sartorius 7.7.1. Company Overview 7.7.2. Product Portfolio 7.7.3. Recent Developments and Future Outlook 7.8. BD Biosciences 7.8.1. Company Overview 7.8.2. Product Portfolio 7.8.3. Recent Developments and Future Outlook 7.9. Lonza 7.9.1. Company Overview 7.9.2. Product Portfolio 7.9.3. Recent Developments and Future Outlook 7.10. CellGenix 7.10.1. Company Overview 7.10.2. Product Portfolio 7.10.3. Recent Developments and Future Outlook 7.11. Corning 7.11.1. Company Overview 7.11.2. Product Portfolio 7.11.3. Recent Developments and Future Outlook

8. RECENT DEVELOPMENTS AND INITIATIVES 8.1. Chapter Overview 8.2. Partnership Models 8.3. Cell Therapy Consumables: Recent Partnerships and Collaborations 8.4. Cell Therapy Consumables: Recent Expansions

9. LIKELY PARTNER ANALYSIS FOR CELL THERAPY CONSUMABLE PROVIDERS 9.1. Chapter Overview 9.2. Scoring Criteria and Key Assumptions 9.3. Scope and Methodology 9.4. Key Potential Strategic Partners for Cell Therapy Consumable Providers 9.3.1. Likely Partner Opportunities for Dendritic Cell Therapy Consumable Providers 9.3.2. Likely Partner Opportunities for NK Cell Therapy Consumable Providers 9.3.3. Likely Partner Opportunities for Stem Cell Therapy Consumable Providers 9.3.4. Likely Partner Opportunities for T-Cell Therapy Consumable Providers

10. DEMAND ANALYSIS 10.1. Chapter Overview 10.2. Scope and Methodology 10.3. Global Demand for Cell Therapy Consumables 10.4. Global Demand for Cell Therapy Consumables for Planar Processes 10.5. Global Demand for Cell Therapy Consumables for Suspension Processes 10.6. Analysis by Scale of Operation 10.7. Analysis by Region

11. MARKET FORECAST AND OPPORTUNITY ANALYSIS 11.1. Chapter Overview 11.2. Forecast Methodology 11.3. Global Outsourced Cell Therapy Consumables Market, 2021-2031 11.4. Outsourced Cell Therapy Consumables Market, 2021-2031: Distribution by Type of Consumable 11.5. Outsourced Cell Therapy Consumables Market, 2021-2031: Distribution by Type of Cell Therapy 11.6. Outsourced Cell Therapy Consumables Market, 2021-2031: Distribution by Scale of Operation 11.7. Outsourced Cell Therapy Consumables Market, 2021-2031: Distribution by Type of End-User 11.8. Outsourced Cell Therapy Consumables Market, 2021-2031: Distribution by Geography

12. UPCOMING TRENDS AND FUTURE GROWTH OPPORTUNITIES 12.1. Chapter Overview 12.2. Emerging Trends Related to Cell Culture Media 12.3. Automation of Cell Therapy Manufacturing Processes 12.4. Single Use Systems and Technologies in Cell Therapy Manufacturing

13. IMPACT OF COVID-19 ON CELL THERAPY CONSUMABLES MARKET 13.1. Chapter Overview 13.2. Impact of COVID-19 Pandemic on Cell Therapy Consumables Market 13.3. Impact on Future Market Opportunities for Cell Therapy Consumable Providers 13.4. Current Opinions and Key Initiatives of Key Players 13.5. Recuperative Strategies for Developer Businesses 13.5.1. Strategies for Implementation in the Short / Mid Term 13.5.2. Strategies for Implementation in the Long Term

14. CONCLUDING REMARKS 14.1. Chapter Overview

15. INTERVIEW TRANSCRIPTS 15.1. Chapter Overview 15.2. Anant Kamath, Chief Operating Officer, Cellular Engineering Technologies 15.2.1. Cellular Engineering Technologies: Key Highlights 15.2.2. Interview Transcript 15.3. Vishal G. Warke, Director R&D, Cell Culture and Immunology, HiMedia Laboratories and Gauri W. Page, Assistant R&D Manager, Animal Cell Culture, Himedia Laboratories 15.3.1. HiMedia Laboratories: Key Highlights 15.3.2. Interview Transcript

16. APPENDIX I: TABULATED DATA

17. APPENDIX II: LIST OF COMPANIES AND ORGANIZATIONS

For more information about this report visit https://www.researchandmarkets.com/r/2t5jj1

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716

SOURCE Research and Markets

http://www.researchandmarkets.com

Read more here:
Worldwide Cell Therapy Consumables Industry to 2031 - Featuring Bio-Techne, Irvine Scientific and Sartorius Among Others - PRNewswire

Newer Agents for DLBCL Show Potential for Earlier Use in the Course of Treatment – Targeted Oncology

The most common frontline treatment for diffuse large B cell lymphoma (DLBCL) is cyclophosphamide, doxorubicin, vincristine sulfate, and prednisone (CHOP). However, approximately 1 in 3 patients relapse after CHOP, and alternative therapies are still needed.

According to Jason Westin, MD, the leader of the DLBCL research team at the University of Texas MD Anderson Cancer Center, the strategies for DLBCL treatment have not changed drastically since the mid 1970s. Additionally, more information is needed as to why patients relapse after CHOP.

For patients who are CHOP resistant, the standard of care is strong chemotherapy followed by an autologous stem cell transplant. However, according to Westin, more personalized and targeted therapies are needed.

In an interview with Targeted OncologyTM, Westin discussed the future of DLBCL treatment in both the frontline and later-line settings, along with current unmet clinical needs.

TARGETED ONCOLOGY: Can you give a background on current treatments in DLBCL?

WESTIN: DLBCL is the most common lymphoid cancer in adults, it's diagnosed in about 30,000 people each year in the US. And the treatments of that most common lymphoid cancer have been effectively stuck in the 1970s and the 1990s. We use a combination chemotherapy approach called CHOP, which was originally prescribed in 1976. We've changed a lot in life from 1976 to now, but we're still using this old combination chemotherapy in the curative setting for lymphoma. So obviously, new approaches are needed.

What does the current DLBCL treatment landscape?

Most patients are treated with the combination chemotherapy CHOP, and that cures approximately 2/3 of patients. It's a fairly effective standard therapy. However, at least 1 out of 3 people need additional treatments, and we don't do as well in the relapse setting as we'd like. So, we're constantly trying to innovate and improve that frontline setting and get beyond the 2/3 cure rate with initial treatments, and that will take a better understanding of why those 1/3 don't respond to CHOP, and a better understanding of the biology of what makes them resistant to treatments.

Do we know anything right now about the mechanisms of resistance to CHOP?

We know some, but I argue that we don't nearly know as much as we think we do. We understand the biology in the sense of understanding which mutation is present, or what type of gene signature. But often, the actual reason as to why a given patient doesn't respond to CHOP is very poorly understood. Patients that have the same biopsy, same genetic signature, some of those patients are cured and some of those patients are resistant. And it's difficult to predict prior to therapy which of those patients are resistant.

For patients that are resistant to CHOP, what options exist for them?

The standard of care for the past 20 years for those resistant to CHOP has been strong chemotherapy followed by an autologous stem cell transplant. Beyond the second line setting right now, there are a number of FDA approved agents for patients with relapsed BLBCL, and many of those FDA approved agents are being studied in combination CHOP and rituximab [Rituxan; R-CHOP].

What clinical needs are still unmet in this patient population?

The needs that are still unmet are finding more personalized therapies, specifically for those patients who are not cured with R-CHOP. But I would argue even in those patients who are currently cured with R-CHOP, that we don't want to use 1970s, chemotherapy in 2050. We want to be able to have personalized approaches and be able to move beyond effectively sledgehammer kind of blunt force instruments and use more precision medicine. So, we clearly need to do better urgently for the folks who are currently resistant or not responsive to chemotherapy. But I'd argue in the long run we need to do better across the board.

Do you see more aggressive approaches like autologous stem cell transplant and targeted therapies moving to the frontline setting in the future? Or do you think they'll remain a second- and third-line option?

I think that CAR T cells have the potential to move to the frontline for a subset of patients, for those that are not going to be responsive to our standard treatments. I think that's an approach that has merit, to try and use a powerful weapon at an earlier time point. I don't think stem cell transplant will do that. But I do think some of the other targeted therapies, the antibody drug conjugates, the bispecific antibodies, antibodies in combination with other immune therapies do potentially have a role to play in the frontline setting.

Where do you see the DLBCL space going in the next 5 to 10 years?

Well, I'd love to say things will be dramatically different. But we could have said that at any point over the last 20 years and would have been wrong. There are multiple ongoing studies looking at ways to improve the frontline setting. But innovation is more likely in the relapse space, which then filters up to the frontline space. And I think that the CAR T-cell studies showing potential advantages in the second line will change the landscape for patients who have relapsed after R-CHOP in the next 5 to 10 years to favor using CAR T-cell therapy. I think based on having that better cure fraction in the relapse space, more innovation may be possible in the frontline space. And so therefore doing studies that are not handcuffed to the 1970s chemotherapy for fear of not giving a patient the old curative therapy and missing a potential window for cure, I think that will allow us to do more innovative studies. I've done a handful of clinical trials using targeted therapy combinations prior to chemotherapy. And what we've shown in those studies is the response rates are very high. And patients tolerate it very well. And so that's still on a clinical trial stage. But it does show the potential that these targeted treatments can work better in newly diagnosed patients and potentially forego the need for chemotherapy.

I think the R-CHOP plus combination trial designs a failure. And I think that more innovative trial designs are needed. But clinical research still remains the best weapon we have to fight cancer in general and specifically DLBCL.

Go here to read the rest:
Newer Agents for DLBCL Show Potential for Earlier Use in the Course of Treatment - Targeted Oncology

International ZIM Network: SmartMed – Regenerative Solutions for the Therapies of Tomorrow – Business Wire

DUESSELDORF, Germany--(BUSINESS WIRE)--The kick-off for the first SmartMed network meeting (digital) took place on Thursday, October 14th. Almost all network partners were able to attend the 2.5-hour event and exchanged ideas on current and potential projects. The focus here was on getting to know each other as well as targeted networking. With the help of a modern network platform, the participants were encouraged to exchange ideas in virtual chat rooms about the topics of digitization and artificial intelligence, new materials for restoring or healing tissue and organs and new approaches to stem cell therapy.

The next network meeting is planned for the beginning of December 2021. The network partners largely determine the focus of the next meeting themselves; Depending on requirements, either a cross-network workshop or a lecture on a specific topic from the field of regenerative medicine is prepared.

About SmartMed: The international ZIM cooperation network "Regenerative Solutions for Tomorrow's Therapy" is funded by the Federal Ministry for Economic Affairs and Energy as part of the ZIM program (Central Innovation Program for SMEs). The network management of Silversky LifeSciences GmbH launched the association with technological competencies from blockchain to the regulation of medical devices at the beginning of July 2021. Networking is coordinated by Silversky LifeSciences with its business start-up experts with a technology focus in LifeSciences and with extensive experience in the financing, operation, and development of innovative small and medium-sized companies in this sector. "Each partner brings a certain specialist knowledge and thus a unique contribution to the value chain into the network", describes Dr. Mirko Stange, founder, and CEO of Silversky LifeSciences, the win-win situation for everyone involved.

The international focus is on UK, which also offers German network partners a good opportunity to react to the new framework conditions, especially after Brexit and the associated reorganization of international cooperation. The project is supported by the international network management team Maria Fenner, Lena Ehrenpreis and Jessica Stolzenberg. "The aim of the network is to network companies with R&D institutions in order to initiate a lively innovation policy, to promote startups and to promote the exchange and cooperation of regenerative medicine with related industries", says Jessica Stolzenberg. We want to give all SMEs and startups in the industry the opportunity to expand their network and find new cooperation partners. If there is still funding for my own research activities, I don't know who would turn it down, says Lena Ehrenpreis. Maria Fenner adds: Our focus is on the entire field of regenerative medicine and the development of innovative, regenerative therapies, which are based on the latest scientific findings and use the most modern technologies. The focus is on restoring the healthy and functional original state of the affected tissue / organ by linking modern therapeutic approaches, new and functional materials, as well as the use of digital and intelligent systems in the form of algorithms, deep learning and AI. "

The support provided by the network includes advice and practical help with the market launch, applying for grants, close collaboration between experts in order to research or optimize new therapy methods and to bring products to market maturity. All interested parties are cordially invited to contact the network managers to join the discussion, make contacts and start exciting projects.

Originally posted here:
International ZIM Network: SmartMed - Regenerative Solutions for the Therapies of Tomorrow - Business Wire

BioLineRx Announces Positive Results from Pharmacoeconomic Study Positioning Motixafortide as Potential Standard of Care in Stem Cell Mobilization -…

TEL AVIV, Israel, Oct. 13, 2021 /PRNewswire/ --BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a late clinical-stage biopharmaceutical company focused on oncology, today announced positive results from a pharmacoeconomic study evaluating the cost-effectiveness of using investigational drug Motixafortide as a primary stem cell mobilization (SCM) agent on top of granulocyte colony stimulating factor (G-CSF), versus G-CSF alone, in multiple myeloma patients undergoing autologous stem cell transplantation (ASCT). The study was performed by the Global Health Economics and Outcomes Research (HEOR) team of IQVIA, and was a pre-planned study conducted in parallel with the GENESIS Phase 3 trial. These results, together with the highly significant and clinically meaningful data from the GENESIS trial, strongly support the potential use of Motixafortide, on top of G-CSF, as the standard of care in SCM for ASCT.

The study concluded that the addition of Motixafortide to G-CSF (the current standard of care) is associated with a statistically significant decrease in health resource utilization (HRU) during the ASCT process, compared to G-CSF alone. Based on the significantly higher number of mobilized cells and the lower number of apheresis sessions, lifetime estimates show quality-adjusted-life-year (QALY) benefits and net cost savings of ~$17,000 (not including the cost of Motixafortide), versus G-CSF alone. The study findings, combined with model estimates, suggest that the use of Motixafortide, on top of G-CSF, as the standard of care in mobilization for ASCT, could be a cost-effective option in the US, based on accepted willingness-to-pay (WTP) values for healthcare payers.

"The compelling cost savings identified by this rigorously designed study strongly support the Company's view that Motixafortide, in combination with G-CSF, can become the new standard of care as an upfront, or primary, therapy for all multiple myeloma patients undergoing autologous stem cell transplantation," stated Philip Serlin, Chief Executive Officer of BioLineRx. "Based on data from the GENESIS trial showing that nearly 90% of patients collected an optimal number of cells for transplantation following a single administration of Motixafortide and in only one apheresis session, versus less than 10% for G-CSF alone, the pharmacoeconomic study demonstrates that use of Motixafortide on top of G-CSF can save $17,000 per patient, not including the cost of Motixafortide. These cost savings should leave substantial room in the future to optimize our pricing strategy for Motixafortide at product launch and thereafter, if approved.

"It is also important to note that fewer administrations and apheresis sessions confer meaningful safety and time benefits to patients. In addition, the significantly higher median number of cells collected in one apheresis session ~11 million using Motixafortide on top of G-CSF versus ~2 million for G-CSF alone not only enables transplantation of an optimal number of cells, with the potential to significantly save on time to engraftment, it also permits the retention of enough cells for cryopreservation in the event that an additional transplantation is required in the future. Lastly, higher levels of certainty regarding the number of apheresis sessions required for mobilization could enable more efficient utilization of apheresis units at transplantation institutions, where there is often a shortage of available machines.

"We believe the data from the GENESIS study, together with the results from this pharmacoeconomic study, set Motixafortide apart from all other mobilization agents either currently available or in development. If approved, Motixafortide represents a significant advancement in SCM to the benefit of patients and payers alike, and, to that end, we remain on track to submit a New Drug Application (NDA) to the FDA in the first half of next year," Mr. Serlin concluded.

About the Pharmacoeconomic Study

The pharmacoeconomic study analyzed healthcare resource utilization (HRU) observed during the Phase 3 GENESIS trial, which randomized 122 patients into two arms: Motixafortide plus G-CSF (n=80) or placebo plus G-CSF (n=42). HRU data points collected include: (1) the number of Motixafortide and G-CSF doses, as well as the number of apheresis sessions performed, in primary mobilization; (2) the percentage of patients needing rescue mobilization due to poor primary mobilization, including the number of apheresis sessions needed and the number of G-CSF and plerixafor doses required; and (3) hospitalization costs related to conditioning and transplantation, including length of stay. Quality-adjusted life years gained (QALY) from published literature were also incorporated into the model. Motixafortide plus G-CSF was associated with a statistically significant HRU decrease during the autologous stem cell transplantation process compared to standard-of-care G-CSF alone. Given the higher number of mobilized cells and lower number of apheresis sessions, lifetime estimates show quality-adjusted-life-year (QALY) benefits and net cost savings of ~$17,000 (not including the cost of Motixafortide), versus the current standard of care.

About the GENESIS Phase 3 Trial

The GENESIS Phase 3 trial (NCT03246529) was initiated in December 2017. GENESIS was a randomized, placebo-controlled, multicenter study, evaluating the safety, tolerability and efficacy of Motixafortide and G-CSF, compared to placebo and G-CSF, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. The primary objective of the study was to demonstrate that only one dose of Motixafortide on top of G-CSF is superior to G-CSF alone in the ability to mobilize 6 million CD34+ cells in up to two apheresis sessions. Additional objectives included time to engraftment of neutrophils and platelets and durability of engraftment, as well as other efficacy and safety parameters. The study successfully met all primary and secondary endpoints with an exceptionally high level of statistical significance (p<0.0001), including approximately 90% of patients who mobilized the target number of cells for transplantation with only one administration of Motixafortide and in only one apheresis session.

About Stem Cell Mobilization for Autologous Stem Cell Transplantation

Autologous stem cell transplantation (ASCT) is part of the standard treatment paradigm for a number of blood cancers, including multiple myeloma, non-Hodgkin's lymphoma and other lymphomas. In eligible patients, ASCT is performed after initial (induction) therapy, and, in most cases, requires consecutive-day clinic visits for the mobilization and apheresis (harvesting) phases, and full hospitalization for the conditioning chemotherapy and transplantation phases until engraftment. The associated burden is therefore significant patients experience clinically relevant deteriorations in their quality of life during ASCT, and healthcare resource use throughout the ASCT phases is particularly intense. Therefore, new interventions impacting the ASCT process have the potential for relieving some of the clinical burden for transplanted patients, the logistical burden for the apheresis units, and the financial burden for healthcare providers and payers.

Described simply, ASCT consists of: (1) mobilizing the patient's own stem cells from his/ her bone marrow to the peripheral blood for removing (harvesting) via an apheresis procedure; (2) freezing and storing the harvested cells until they are needed for transplantation; (3) providing a conditioning treatment, such as high-dose chemotherapy or radiation, to kill the remaining cancer cells the day before transplant; and (4) infusing the stored stem cells back to the patient intravenously via a catheter.

To mobilize the patient's stem cells from the bone marrow to the peripheral blood for harvesting, the current standard of care includes the administration of 5-8 daily doses of granulocyte colony stimulating factor (G-CSF), and the performance of 1-4 apheresis sessions. For patients unable to mobilize sufficient numbers of cells for harvesting during this primary mobilization phase, rescue therapy is carried out, consisting of 1-4 doses of plerixafor on top of G-CSF, and the performance of an additional number of apheresis sessions as necessary. In light of this, an agent with superior mobilization activity may significantly reduce the mobilization and harvesting burden and associated risks of the ASCT process and lead to significant clinical and resource benefits.

About BioLineRx

BioLineRx Ltd. (NASDAQ/TASE: BLRX) is a late clinical-stage biopharmaceutical company focused on oncology. The Company's business model is to in-license novel compounds, develop them through clinical stages, and then partner with pharmaceutical companies for further clinical development and/or commercialization.

The Company's lead program, Motixafortide (BL-8040), is a cancer therapy platform that was successfully evaluated in a Phase 3 study in stem cell mobilization for autologous bone-marrow transplantation, as well as reporting positive results from a pre-planned pharmacoeconomic study, and is currently in preparations for an NDA submission. Motixafortide was also successfully evaluated in a Phase 2a study for the treatment of pancreatic cancer in combination with KEYTRUDA and chemotherapy under a clinical trial collaboration agreement with MSD (BioLineRx owns all rights to Motixafortide), and is currently being studied in combination with LIBTAYO and chemotherapy as a first-line PDAC therapy.

BioLineRx is also developing a second oncology program, AGI-134, an immunotherapy treatment for multiple solid tumors that is currently being investigated in a Phase 1/2a study.

For additional information on BioLineRx, please visit the Company's website at http://www.biolinerx.com, where you can review the Company's SEC filings, press releases, announcements and events.

Various statements in this release concerning BioLineRx's future expectations constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "may," "expects," "anticipates," "believes," and "intends," and describe opinions about future events. These forward-looking statements involve known and unknown risks and uncertainties that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Factors that could cause BioLineRx's actual results to differ materially from those expressed or implied in such forward-looking statements include, but are not limited to: the initiation, timing, progress and results of BioLineRx's preclinical studies, clinical trials and other therapeutic candidate development efforts; BioLineRx's ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; BioLineRx's receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings and approvals; the clinical development, commercialization and market acceptance of BioLineRx's therapeutic candidates; BioLineRx's ability to establish and maintain corporate collaborations; BioLineRx's ability to integrate new therapeutic candidates and new personnel; the interpretation of the properties and characteristics of BioLineRx's therapeutic candidates and of the results obtained with its therapeutic candidates in preclinical studies or clinical trials; the implementation of BioLineRx's business model and strategic plans for its business and therapeutic candidates; the scope of protection BioLineRx is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; estimates of BioLineRx's expenses, future revenues, capital requirements and its needs for additional financing; risks related to changes in healthcare laws, rules and regulations in the United States or elsewhere; competitive companies, technologies and BioLineRx's industry; risks related to the COVID-19 pandemic; and statements as to the impact of the political and security situation in Israel on BioLineRx's business. These and other factors are more fully discussed in the "Risk Factors" section of BioLineRx's most recent annual report on Form 20-F filed with the Securities and Exchange Commission on February 23, 2021. In addition, any forward-looking statements represent BioLineRx's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law.

Contact:Tim McCarthy LifeSci Advisors, LLC +1-212-915-2564 [emailprotected]

or

Moran Meir LifeSci Advisors, LLC +972-54-476-4945 [emailprotected]

SOURCE BioLineRx Ltd.

Read the original here:
BioLineRx Announces Positive Results from Pharmacoeconomic Study Positioning Motixafortide as Potential Standard of Care in Stem Cell Mobilization -...

FTC Follows Through On Prioritizing Investigations Into False Advertising In Healthcare Markets – Media, Telecoms, IT, Entertainment – United States -…

15 October 2021

Perkins Coie LLP

To print this article, all you need is to be registered or login on Mondaq.com.

Key Takeaways:

On July 1, 2021, the FTC adopted aseries of resolutionsauthorizing investigations into several areas designated as key law enforcement priorities during the next ten years.One of those resolutionsdesignates "acts or practices affecting healthcare markets" as an enforcement priority.

In the months after adopting this broad mandate, the FTC has actively pursued false and deceptive advertising in healthcare markets.

For example, on August 16, 2021, the FTC and the Georgia Attorney Generalsuedthe co-founders of the Stem Cell Institute of America for false marketing in advertising stem cell therapy to seniors. Specifically, the defendants advertised their stem cell therapies as effectively treating orthopedic conditions and diseases. The FTC and the Georgia Attorney General alleged that the defendants never conducted any randomized clinical testing of the treatments to support these claims and that no other studies exist demonstrating that stem cell treatments are effective in treating any orthopedic conditions or diseases.

Similarly, in early September 2021, theFTC sent cease-and-desist lettersto ten different companies demanding that they, among other things, stop selling unapproved diabetes products and making efficacy claims that are not supported by sufficient evidence.

These two actions, coming on the heels of the resolution prioritizing enforcement in the healthcare industry, may portend aggressive FTC policing of healthcare-related advertising. Accordingly, companies offering healthcare services or productsespecially those offering treatmentsshould ensure that their advertisements are backed up by competent and reliable scientific evidence.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

POPULAR ARTICLES ON: Media, Telecoms, IT, Entertainment from United States

Bryan Cave Leighton Paisner LLP

With government support instigated by the Covid-19 pandemic coming to an end, there is an inevitability that some hotel owners will sadly not have the liquidity to continue to operate in the medium term.

See original here:
FTC Follows Through On Prioritizing Investigations Into False Advertising In Healthcare Markets - Media, Telecoms, IT, Entertainment - United States -...

Molecular Atlas of Small Cell Lung Cancer Reveals Unusual Cell Type That Could Explain Why Its So Aggressive – On Cancer – Memorial Sloan Kettering

Imagine youre about to go on a cross-country trip, stopping at spots along the way to admire local attractions. Youd probably want to have a road atlas handy, containing maps at different scales, covering both the major highways and the roads of smaller cities and towns or at least a GPS that can access a digital atlas with this information.

Until recently, cancer researchers have been like cross-country travelers with only a few maps of a few popular cities. And because of how fast some cancers grow, the maps quickly go out of date. This situation has hindered doctors ability to understand whats really going on inside tumors and develop effective treatments.

The Human Tumor Atlas Network (HTAN) was created to change that. It aims to develop high-resolution maps of many kinds of cancer so that doctors could have a more-complete view of the textured terrain of tumors including how they change over time to become more deadly. HTAN is funded by the National Cancer Institute and involves a consortium of cancer centers across the United States.

After several years of painstaking research, the first such atlas from investigators at Memorial Sloan Kettering Cancer Center for small cell lung cancer is now ready for viewing, and its full of new insights.

The most exciting thing we found is a rare population of stem-like cells within these tumors that is closely correlated with patient outcomes, explains Charles Rudin, a physician-scientist at MSK who co-led the lung cancer project. The more enriched they are in the tumor, the worse the prognosis.

Not only that, but these stem-like cells have metastatic properties meaning theyre prone to spread and researchers found them across many SCLC tumors that otherwise were very different.

That was a massive surprise, says Dana Peer, a computational biologist at MSK who is a principal investigator of the HTAN and co-led the lung cancer atlas project. It raises the possibility that this tiny fraction of cells could be driving metastatic behavior across tumors.

Small cell lung cancer is one of the deadliest cancers. It tends to spread early and aggressively; two-thirds of cases are already metastatic at diagnosis. Chemotherapy is not very effective. The researchers hope their new atlas, which was published October 14, 2021, in the journal Cancer Cell, will lead to improvements in care for people with the disease.

Building the atlas required years of collaborative work from two groups with very different areas of expertise: clinicians like Dr. Rudin with disease-specific expertise in small cell lung cancer and computational biologists like Dr. Peer and her team.

Dr. Rudin points to the fact that there are four co-first authors on the paper an unusual occurrence as evidence of the diversity of skillsets needed to complete a study like this. The co-first authors are Joseph Chan, lvaro Quintanal-Villalonga, Vianne Ran Gao, and Yubin Xie.

Dr. Peer, Chair of the Computational and Systems Biology Program at the Sloan Kettering Institute, took the lead on the computational side of things. She is an expert in single-cell RNA seq (scRNAseq), a technique that allows scientists to get a detailed picture of which genes are turned on in many hundreds of cells at the same time.

By applying scRNAseq to SCLC tumor specimens obtained from patients at MSK, Dr. Peer and her team were able to find this rare population of stem cell-like cells lurking amidst the cells of the surrounding tumor, like locating a needle in a haystack.

We would never have been able spot these cells with bulk sequencing. We really needed single cell analysis to find them.

We would never have been able spot these cells with bulk sequencing, she says. We really needed single cell analysis to find them. (Bulk sequencing is what researchers would do before scRNAseq was available essentially putting the tumor in a blender and sequencing all the RNA that fell out.)

The single cell technique also allowed the team to go further. Within the cells making up this tiny population, one gene stood out: PLCG2. This gene makes a protein that acts as a second messenger it relays signals from one protein to another.

PLCG2 did not initially strike me as the sort of gene that would be involved in regulating stem cell populations, Dr. Rudin says. It seems like more of a worker bee.

But indeed, PLCG2 does seem to be playing an important role. The gene is most highly expressed in this stem cell-like population, the scientists found. And when they experimentally increased or lowered its activity in cancer cell lines, it altered the ability of the cancer cells to metastasize.

They researchers think that these PLCG2-high cells could be part of the explanation for SCLCs aggressiveness. If so, it could open up new possibilities for treatment.

The thought is that if we can develop strategies to selectively target this cell population, we might be able to suppress metastasis and ultimately improve outcomes for patients with small cell lung cancer, Dr. Rudin says.

What we really want to do is try to stop metastasis in its tracks, Dr. Peer adds. But to do that, we need to better understand these rare cell populations that seem to be driving it. Thats the goal of this atlas.

Key Takeaways

More here:
Molecular Atlas of Small Cell Lung Cancer Reveals Unusual Cell Type That Could Explain Why Its So Aggressive - On Cancer - Memorial Sloan Kettering

Actress Jennifer Garner Visits with 7-Year-Old Girl Fighting B-cell Acute Lymphoblastic Leukemia; What is the Treatment for This Disease? -…

7-year-old Michigan resident Aubrielle is fighting leukemia, and shes getting some love and attention from a golden-hearted celeb: Actress Jennifer Garner.

Garner, whos also a mom to three children she shares with former partner Ben Affleck, visited with Aubrielle via video call. The call was facilitated by Childrens Miracle Network, a non-profit that raises money for childrens hospitals in North America.

Acute Lymphoblastic Leukemia (ALL) is a type of cancer of the blood and bone marrow. Aubrielle was diagnosed with this disease specifically, she was diagnosed with B-cell Acute Lymphoblastic Leukemia in September 2020. She had 9 months of treatment, and her condition has improved, reported WCRZ. Moments like her time with Garner have raised Aubrielles spirits through her cancer journey.

Related: Illusionist Criss Angel And Wife Celebrate Immunotherapys Impact On Sons Leukemia: Bloods Were Amazing Today

Leukemia is the most common cancer diagnosed in children and teens. It accounts for almost 1 out of 3 cancers. On the whole, though, pediatric leukemia is a rare disease.

The American Cancer Society says that approximately 3 out of 4 leukemias among children and teens are acute lymphocytic leukemia (ALL). Most of the remaining cases are acute myeloid leukemia (AML). ALL is most common in early childhood, peaking between 2 and 5 years of age, says the ACS.

What Is Acute Lymphoblastic Leukemia ALL?

Treatment options for this type of cancer, B-cell Acute Lymphoblastic Leukemia, include chemotherapy, radiation therapy, stem cell transplant, and in some cases, immunotherapy.

Related: Recovering From A Stem Cell Transplant

Immunotherapy drugs use a patients immune system to identify and destroy cancer cells. Several types of immunotherapy have been approved for use against childhood leukemia, according to the ACS.

In an earlier interview, Dr. Olalekan Oluwole, a hematologist with Vanderbilt University Medical Center, explains the steps that may follow an Acute Lymphoblastic Leukemia (ALL) diagnosis. He says,Cancer is a really life-changing diagnosis. And we would like our patients to know that they dont have to feel that they are in there on their own. We have case managers that can help. We have social workers.

Related: The Value of Using a Social Worker During Treatment

In fact, we have a navigator because sometimes they have blood test here, they see a doctor there, they get chemo there, they do a lumbar puncture. It can be completely overwhelming. So we actually have people that can help them find their way around the hospital, he says.

The Next Steps After an Acute Lymphoblastic Leukemia ALL Diagnosis

Learn more about SurvivorNet's rigorous medical review process.

See more here:
Actress Jennifer Garner Visits with 7-Year-Old Girl Fighting B-cell Acute Lymphoblastic Leukemia; What is the Treatment for This Disease? -...

Four-year-old girl with stage four cancer trying to get to America for clinical trial – Lancashire Telegraph

The parents of a four-year-old girl with advanced cancer are asking for help to get their daughter to America for pioneering treatment.

Four-year-old Maysaa Arrami, from Burnley, was diagnosed with stage four neuroblastoma a rare and highly aggressive form of childhood cancer at the end of March 2020, just as the country was plunged into lockdown.

Maysaa had become very clingy and went off certain foods before her mother, Ihssane Arrami noticed her daughters lips were turning blue and her stomach was swollen.

Ihssane took her to the GP who referred Maysaa to a cardiologist but due to long wait times for referrals, her father Osama Arrami decided to take to her to Burnley General Hospital urgent care centre.

The doctor sent her to Royal Blackburn Hospital, where the doctors further referred her to Manchester Childrens Hospital who returned a diagnosis of stage 4 high-risk neuroblastoma.

Osama said: At that point I didnt quite understand. I am not even sure the word tumour was used.

The penny never really dropped at that point. The doctor could see that and elaborated and at that point I just broke down. It was an emotional experience.

Maysaa was put on chemotherapy, receiving five rounds before having surgery where they managed to remove about 95 per cent of the tumour.

She then had a further session of chemo before having a stem cell transplant which led her to developing mucositis, an inflamed mouth which is a common side effect of the therapy.

Osama said: Its been really, really difficult to just see our daughter have to endure the treatment and the sad effects that came with it.

She was asking us why her hair was falling out or why we had shaved it.

Some of the drugs would change her behaviour and so she was more anxious or she would be quite angry.

Generally, she wasnt eating so she had to have tubes put in her nose.

Maysaa will now have to have undergo 14 days of radiation therapy and six months of immunotherapy.

Osama said it is difficult to think that he and his wife are nursing Maysaa back to health so she is able to have another round of treatment done.

He said: We are nursing her back to health ready for the next battle she has to undergo.

When we give ourselves the time to think about it, its quite upsetting.

All we are doing is getting her back to a point where she can have the treatment.

The treatment is working and now the family are asking for help fundraising so that they can travel to America several times over two years for a clinical trial which they hope will keep the cancer away.

If the cancer does return, there is a very poor chance of survival. High-risk neuroblastoma carries a high chance of returning therefore we want Maysaa to receive this treatment as soon as possible after her end of UK treatment scans. Osama concluded.

If you wish to help the family you can do so by donating on their page on the Solving Kids Cancer website and searching for 'Maysaa'.

Read the original:
Four-year-old girl with stage four cancer trying to get to America for clinical trial - Lancashire Telegraph

Stem cell & gene therapy to treat osteogenesis imperfecta: hype or hope – Open Access Government

A genetic syndrome that affects bones

Osteogenesis Imperfecta (OI) is a hereditary disorder occurring in 1:10,000 births and characterised by osteopenia (bone loss) and skeletal fragility (fractures). Secondary features include short stature, skeletal deformities, blue sclera and dentinogenesis imperfect. (1) There is a large clinical variability in OI, and severity ranges from mild to lethal, based on radiological characteristics. Genetically, OI is a collagen-related syndrome. Type I collagen is a heterotrimeric helical structure synthesized by bone-forming cells (osteoblasts), and it constitutes the most abundant protein of the skeletal organic matrix. (2) Synthesis of type I collagen is a complex process. (3) Collagen molecules are cross-linked into fibrils (which confer tensile strength to the bones). Those are then mineralised by hydroxy-apatites (which provides compressive strength) and assembled into fibres.

Dominant mutations in either the COL1A1 or the COLA1A2 genes are responsible for up to 90% of all OI cases. These mutations (more than 1,000 of which have been identified) lead to impairment of collagen structure and production, which in either quantitative or qualitative bone extracellular matrix (ECM) defects. Mutations affecting ECM structure have serious health consequences because the skeleton protects visceral organs and the central nervous system and provides structural support. Bones also store fat in the yellow bone marrow found within the medullary cavity, whilst the red marrow located at the end of long bones is the site of haematopoiesis. In addition, the ECM constitutes a reservoir of phosphate, calcium, and growth factors, and is involved in trapping dangerous molecules.

Stem cell therapy for OI aims to improve bone quality by harnessing the ability of mesenchymal stem cells (MSC) to differentiate into osteoblasts, with the rationale that donor cells would engraft into bones, produce normal collagen and function as a cell replacement. Stem cells have, therefore, been proposed for the treatment of OI (4) and, in particular, prenatal foetal stem cell therapy (foetal stem cells injected into a foetus, i.e. foetal-to-foetal) approach, which offers a promising route to effective treatment. (5) Human foetal stem cells are more primitive than stem cells isolated from adult tissues and present advantageous characteristics compared to their adult counterparts, i.e. they possess a higher level of plasticity, differentiate more readily into specific lineages, grow faster, senesce later, express higher levels of adhesion molecules, and are smaller in size. (6,7) Prenatal cell therapy capitalises on the small size of the foetus and its immunological naivete. In addition, stem cells delivered in utero benefit from the expansion of endogenous stem cells and may prevent organ injury before irreversible damage. (8)

However, human foetal stem cells used are isolated from either foetal blood drawn by cardiac puncture, either during termination of pregnancy or during ongoing pregnancy, albeit using an invasive procedure associated with a high risk of morbidity and mortality for both the foetus and the mother (9). Foetal cells can also be isolated from the first-trimester liver (following termination of pregnancy) and such cells are currently used in The Boost Brittle Bones Before Birth (BOOSTB4) clinical trial, which aims to investigate the safety and efficacy of transplanting foetal derived MSCs prenatally and/or in early postnatal life to treat severe Osteogenesis Imperfecta (OI) (10). Alternatively, foetal stem cells can be isolated during ongoing pregnancy from the amniotic fluid, either during mid-trimester amniocentesis or at birth (11,12) or from the chorionic villi of the placenta during first-trimester chorionic villi sampling (13).

We have demonstrated that human fetal stem cells isolated from first trimester blood possess superior osteogenic differentiation potential compared to adult stem cells isolated from bone marrow and to fetal stem cells isolated from first trimester liver. We showed that in utero transplantation of these cells in an experimental model of severe OI resulted in a drastic 75% decrease in fracture rate incidence and skeletal brittleness, and improvement of bone strength and quality.(14) A similar outcome was obtained using placenta-derived foetal stem cells (15) and amniotic fluid stem cells following perinatal transplantation into experimental models. (16,17)

Understanding the mechanisms of action of donor cells will enable the engineering of donor cells with superior efficacy to stimulate bone formation and strengthen the skeleton. Despite their potential to differentiate down the osteogenic lineage, there is little evidence that donor cells contribute to regenerating bones through direct differentiation, due to the very low level of donor cell engraftment reported in all our studies. When placed in an osteogenic microenvironment in vitro, foetal stem cells readily differentiate into osteoblasts and produce wild type collagen molecules. However, there are insufficient proofs that collagen molecules of donor cell origin contribute to the formation of the host bone ECM to confer superior resistance to fracture.

It is now well accepted that stem cells can influence the behaviour of target cells through the release of paracrine factors and, therefore, contribute to tissue regeneration indirectly. We have indeed recently shown that donor stem cells stimulate the differentiation of resident osteoblasts, which were unable to fully mature in the absence of stem cell treatment. (16,17) We are now focusing our efforts on understanding the precise molecular mechanisms by which donor cells improve skeletal health to counteract bone fragility caused by various OI-causative mutations.

References

Please note: This is a commercial profile

2019. This work is licensed under aCC BY 4.0 license.

Originally posted here:
Stem cell & gene therapy to treat osteogenesis imperfecta: hype or hope - Open Access Government