Stem Cell Clinic

Novartis bags Mesoblast’s stem cell therapy for ARDS, including in Covid-19, in a deal worth up to $1.2B+ – Endpoints News

Novartis has licensed a new stem cell therapy from Mesoblast, just weeks after the FDA rejected the Australian biotechs pitch for an approval on a separate indication.

The Swiss pharma announced Thursday afternoon it is partnering with Mesoblast $MESO to develop remestemcel-L for the treatment of acute respiratory distress syndrome, including ARDS related to Covid-19. As part of the deal, Novartis will shell out $25 million in upfront cash and take a $25 million stake in the biotech, while offering up to $1.255 billion in potential milestone payments.

Mesoblast investors embraced the news, sending shares up 11% on the Australian stock exchange Friday. The companys stock was also up roughly 17% on the Nasdaq before Fridays opening bell.

The milestone payments are split as such, per Mesoblast: $505 million will be available pre-commercialization, with an additional $750 million set aside for hitting certain sales targets and double-digit royalties.

Remestemcel-L, or Ryoncil, acts as an anti-inflammatory and consists of culture-expanded mesenchymal stem cells derived from a bone marrow donor. Currently, the drug is being evaluated in a Phase III study for Covid-19-related ARDS with 300 patients, and the first cut of data is expected in early 2021.

Should that outcome prove successful, Novartis will launch a Phase III in non-Covid ARDS after the deal closes. The companies highlighted Novartis ability to rapidly scale up cell-based therapies from the clinic to the commercial phase as a motivator for the collaboration.

The drug had been examined in a small compassionate use program for Covid-19 ARDS back in March, which included 12 patients requiring ventilators. Remestemcel-L treatment demonstrated an 83% survival rate in that program and was the basis for the ongoing Phase III.

Thursdays deal comes less than two months after the FDA issued a CRL for remestemcel-L in Mesoblasts pediatric acute graft-versus-host disease program. The rejection, which denied the company an accelerated approval, came after an ODAC adcomm in August voted 9 to 1 in favor of approval as panel members struggled to envision what a pivotal trial might look like.

During both the adcomm and in their CRL, regulators took issue with Mesoblasts study design given that the company submitted its application on the basis of one, single-arm and open-label trial. In the study, Remestemcel-L demonstrated a statistically significant benefit in its primary endpoint against the historical control rate.

But because many parents and pediatricians are reluctant to risk putting children into the placebo arm of a randomized study, Mesoblast argued that key opinion leaders said an additional study was not feasible. The veto came despite the FDA approving a similar drug Incyte and Novartis Jakafi based on one single-arm trial, something for which ODAC members chastised the FDA.

Earlier this week, Mesoblast met with the agency for its Type A meeting, and the company reported in its third quarter earnings that it does not expect the FDA to reverse its decision for accelerated approval. Mesoblast is still waiting to receive final meeting minutes to know whether thats indeed the case. The CRL set back potential approval in GvHD from 2021 to 2024, per analysts.

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Novartis bags Mesoblast's stem cell therapy for ARDS, including in Covid-19, in a deal worth up to $1.2B+ - Endpoints News

Global Stem Cells Market is estimated to account for US$ 18289.9 Mn by end of 2027, Says Coherent Market Insights (CMI) – Business Wire

SEATTLE--(BUSINESS WIRE)--The cells of the body are made up of the same basic components, namely: Blood, Muscle, Nerve, Brain, Gut, Respiratory, Skin, Cardiovascular, Urine, and Stem Cells. Each of these cells is unique in its characteristics but all of them play an important role in how healthy your body is and how well it functions.

Blood cells are made up of red blood cells (erythrocytes), platelets (platelet-activating factor) and neutrophils (killer T cells). Unlike blood cells in other organs of the body, white blood cells (white blood cells) do not multiply: they only act as a defense mechanism for the body in the fight against infection and in keeping your immune system active. Blood cells can also be converted to other cells such as platelets and plasma by the action of the protein platelet-activating factor (PAF). When a platelet or plasma cell reproduces, it becomes another cell: a daughter cell. The daughter cell then either becomes a blood cell or goes on to differentiate into a different type of cell such as a red blood cell or a platelet.

The global stem cells market is expected to account for US$ 9941.2 Mn in 2020 in terms of value and is expected to grow at a CAGR of 9.1% during forecast 2020-2027.

Market Drivers:

High prevalence of cancer is expected to propel growth of the global stem cells market over the forecast period. For instance, according to the American Cancer Society, in 2019, there will be an estimated 1,762,450 new cancer cases diagnosed and 606,880 cancer deaths in the U.S.

Moreover, developments towards boosting the availability and use of induced pluripotent stem cell technology is also expected to aid in growth of the market. For instance, in November 2020, FUJIFILM Cellular Dynamics, Inc. partnered with Lonza Walkersville, Inc. to enable drug developers to leverage both companies expertise and technologies for the generation of human induced pluripotent stem cells through licensing agreements.

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Market Opportunities

Potential of stem cell therapy in the treatment of Covid-19 is expected to offer lucrative growth opportunities for players in the global stem cells market. For instance, in November 2020, the randomised, controlled Phase III trial of remestemcel-L in patients with moderate to severe acute respiratory distress syndrome (ARDS) due to COVID-19 infection has been advised to continue by the independent Data Safety Monitoring Board (DSMB).

Moreover, increasing funding for R&D in stem cell therapy is also expected to aid in growth of the market. For instance, in November 2020, Californias stem cell agency will receive an infusion of US$ 5.5 billion in new research funding after voters approved Proposition 14. Similarly, in November 2020, California Institute for Regenerative Medicine awarded a US$ 9 million grant to Diana Farmer and Aijun Wang to help launch the worlds first human clinical trial using stem cells to treat spina bifida, a birth defect that occurs when the spine and spinal cord dont form properly.

Market Trends

Major players operating in the global stem cells market are focused on R&D to expand their product portfolio. For instance, in November 2020, IMAC Holdings, Inc. announced that the company is opening enrollment in its Phase 1 clinical trial for its investigational compound utilizing umbilical cord-derived allogenic mesenchymal stem cells for the treatment of bradykinesia, or the gradual slowing and loss of spontaneous body movement, due to Parkinsons disease.

Competitive Landscape:

Major players operating in the global stem cells market include, Advanced Cell Technology, Inc., FUJIFILM Cellular Dynamics, Inc., Angel Biotechnology Holdings PLC, Bioheart Inc., Lineage Cell Therapeutics., BrainStorm Cell Therapeutics, Inc., IMAC Holdings, Inc., California Stem Cell Inc., Celgene Corporation, Takara Bio Europe AB, Cellular Engineering Technologies, Cytori Therapeutics Inc., Osiris Therapeutics, and STEMCELL Technologies Inc.

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Market segmentation:

About Us:

Coherent Market Insights is a global market intelligence and consulting organization focused on assisting our plethora of clients achieve transformational growth by helping them make critical business decisions. Our client base includes players from across various business verticals in over 57 countries worldwide.

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Global Stem Cells Market is estimated to account for US$ 18289.9 Mn by end of 2027, Says Coherent Market Insights (CMI) - Business Wire

Adherence to Allogeneic Stem Cell Transplantation to Improve Survival in Myelodysplastic Syndromes – Hematology Advisor

With the exception of allogeneic stem cell transplantation (alloSCT) and iron chelation therapy (ICT), many guideline treatments may not improve survival among patients with myelodysplastic syndrome (MDS), according to research published in the Annals of Hematology.

MDS represents a heterogeneous group of malignancies with a variable clinical course, which depends on both disease and patient factors. A number of guidelines help clinicians to recommend treatments based on these characteristics, including European LeukemiaNet (ELN) and the National Comprehensive Cancer Network (NCCN).

It is unknown whether adherence to guideline recommendations improves survival in this patient group. For this study, which had a retrospective cohort and prospective cohort, researchers evaluated whether treatment guideline adherence improves survival among patients with MDS.

All data were obtained from the Duesseldorf MDS Registry. Cohort 1 included data from 1698 patients, to which the researchers applied ELN guidelines retrospectively. Cohort 2 included patients who were given expert-level guidance on MDS treatment.

Overall, in cohort 1, of the treatment options evaluated, adherence to lenalidomide, hypomethylating agents, low-dose chemotherapy, intensive chemotherapy, or best supportive care therapies did not improve patient survival; similar results were found in analyses of cohort 2.

Patients receiving ICT or alloSCT in line with expert guidelines did, however, appear to have improved survival compared with those who were eligible for such treatments but did not receive them. The median survival of patients who were recommended and received ICT was 70 months vs 32 months for eligible patients who did not receive ICT (P =.012). In addition, the median survival for alloSCT-eligible patients who received transplantation compared with patients who did not receive transplantation was 65 months vs 16 months, respectively (P <.0005).

Altogether, our retrospective and prospective analyses imply that, with the exception of alloSCT, none of the currently available therapies is powerful enough to render deviation from guideline-based expert advice a major disadvantage in terms of prognosis, the authors wrote. We clearly need better treatment options, which can really make a change when correctly applied by an MDS expert.

Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Kasprzak A, Nachtkamp K, Kondakci M, et al. Analysis of the impact of adherence to guidelines and expert advice in patients with myelodysplastic syndromes. Ann Hematol. Published online November 7, 2020. doi:10.1007/s00277-020-04325-7

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Adherence to Allogeneic Stem Cell Transplantation to Improve Survival in Myelodysplastic Syndromes - Hematology Advisor

Anakinra: efficacy in the management of fever during neutropenia and mucositis in autologous stem cell transplantation (AFFECT-2)-study protocol for a…

This article was originally published here

Trials. 2020 Nov 23;21(1):948. doi: 10.1186/s13063-020-04847-5.

ABSTRACT

BACKGROUND: Since decades, fever and infections have been the most important complications of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) in the treatment of hematologic malignancies. Neutropenia has long been considered to be the most important risk factor for these complications. However, recent studies have shown that not neutropenia, but the development of mucositis is the most important cause of these complications. Currently, limited options for the prevention and treatment of mucositis are available, of which most are only supportive. The pro-inflammatory cytokine interleukin-1 (IL-1) plays a crucial role in the pathogenesis of mucositis. Pre-clinical studies of chemotherapy-induced mucositis have shown that recombinant human IL-1 receptor antagonist anakinra significantly ameliorated intestinal mucositis. In our pilot study AFFECT-1, we examined the safety and maximal tolerated dose of anakinra in patients with multiple myeloma, treated with high-dose melphalan (HDM) and autologous HSCT, selecting a dose of 300 mg daily for the phase IIb trial. The aim of the AFFECT-2 study is to determine the efficacy of anakinra in preventing fever during neutropenia (FN) and mucositis in this study population.

METHODS/DESIGN: A multicenter, randomized, placebo-controlled, double-blind phase IIb trial will be conducted. Ninety patients with multiple myeloma scheduled for treatment with HDM and autologous HSCT will be included. Patients will be randomized between intravenous treatment with anakinra (300 mg) or placebo. Each group will be treated from day 2 (day of HDM; day 0 is HSCT) up until day + 12. Outcome measures will be assessed at baseline, during admission, at discharge or day + 30, at day + 90, and + 1 year. The primary outcome will be reduction of FN. Secondary outcome measures include mucositis scores, bloodstream infections, citrulline levels, quality of life, and fatigue severity.

DISCUSSION: The AFFECT-2 trial will examine the efficacy of anakinra in the management of fever during neutropenia and mucositis in patients with multiple myeloma treated with HDM and autologous HSCT. The results of this study may provide a new treatment option for these important complications. Also, this study will give us more insight in the pathophysiology of mucositis, including the role of IL-1 and the role of the microbiota in mucositis.

TRIAL REGISTRATION: Clinicaltrials.gov NCT04099901 . Registered on September 23, 2019. EudraCT: 2018-005046-10.

PMID:33225965 | DOI:10.1186/s13063-020-04847-5

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Anakinra: efficacy in the management of fever during neutropenia and mucositis in autologous stem cell transplantation (AFFECT-2)-study protocol for a...

Physical activity is associated with less comorbidity, better treatment tolerance and improved response in patients with multiple myeloma undergoing…

This article was originally published here

J Geriatr Oncol. 2020 Nov 20:S1879-4068(20)30495-1. doi: 10.1016/j.jgo.2020.11.003. Online ahead of print.

ABSTRACT

OBJECTIVES: Multiple myeloma (MM) is the second most common hematological malignancy. Progression free survival (PFS) and overall survival (OS) have substantially improved, nonetheless MM usually remains incurable. Patients with active disease may be affected by numerous comorbidities, including fatigue, depression and osteolytic lesions, which influence their quality of life (QoL). Albeit, it is known that exercising is beneficial for patients QoL, few clinical trials are available in patients with MM. We therefore aimed to compare comorbidities and clinical outcome in physically active and inactive patients with MM.

MATERIAL AND METHODS: We defined physical activity according to WHO criteria (150 min of moderate activity and two sessions of resistance training/week). We matched 53 physically active patients with 53 controls (for age, gender, cytogenetics, disease stage, and therapy) and compared the cohorts for incidence of comorbidities/MM symptoms (osteolytic lesions, anemia, infections, fatigue, depression, Revised-Myeloma Comorbidity Index [R-MCI]) and clinical outcome (treatment tolerance, responses to therapy, PFS and OS) in a retrospective audit. All patients were newly diagnosed with MM and received autologous stem cell transplantations (ASCT) between 2001 and 2017.

RESULTS: Physically active patients showed superior outcomes in R-MCI (p = 0.0005), fatigue (p = 0.0063), treatment tolerance (p = 0.0258) and hospital stays (p = 0.0072). Furthermore, they showed better treatment responses (p = 0.0366), especially complete remission (CR; p = 0.0018) as well as better OS and PFS.

CONCLUSION: Physical activity in patients with MM undergoing ASCT seemed associated with better overall clinical outcome. Randomized clinical trials are required to understand the benefits and devise strategies for improving exercising among patients with MM.

PMID:33223484 | DOI:10.1016/j.jgo.2020.11.003

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Physical activity is associated with less comorbidity, better treatment tolerance and improved response in patients with multiple myeloma undergoing...

CAR T-cell therapy treatment helps cancer patient beat near impossible odds – ABC News

A cancer patient who was given less than a two per cent chance of survival has beaten the odds thanks to a new treatment that alters patient's immune cells to recognise and fight cancer.

Troy Daley was the first person in Australia to trial CAR T-cell therapy to treat mantle cell lymphoma.

The 45-year-old's ordeal began when he discovered a lump in his groin during a shower in 2014 and went to his GP.

"The next thing I knew I was on the operating table having biopsies done and scans done," he said.

About a week later, he was diagnosed with Mantle cell lymphoma a rare type of non-Hodgkin lymphoma.

When Mr Daley was initially diagnosed, his GP told him there was a 98 per cent chance he would be dead within the next six months.

"Telling the family's probably the hardest thing I've ever had to do," he said.

"I had a bit of a slack night that night and the next day I woke up and decided I was too young to fall over and got the gloves on."

Mr Daley was admitted to the Lismore Base Hospital for chemotherapy and received a stem cell transplant in Brisbane, but the treatments were not match for the aggressive cancer.

"(It) came back pretty quick, within sort of six to eight months it was a bit of a shock to everybody," he said.

Mr Daley's haematologist, Dr Dan Scott said he was put on cancer drug Ibrutinib, which worked initially, but after two-and-a-half years his condition progressed.

The next step would have been a bone marrow transplant, but despite a world-wide pool of donors no suitable match could be found.

With almost all the options exhausted, Mr Daley was registered with a clinical trial being done at the Peter MacCallum Cancer Centre in Melbourne.

"It was at a stage where we've got to have a go at something," he said.

"We're not going to sit back here and let the gods come and get me."

CAR T-cell therapy is a new form of immunotherapy that uses specially altered T-cells to directly and precisely target cancer cells.

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Dr Scott said the CAR T-cell trial was used in conjunction with ibrutinib to treat Mr Daley's cancer.

"That's what's been exciting and different about Troy's case is he's had access to this therapy, which is relatively unusual in this disease," he said.

Dr Scott said the results have far exceeded expectations.

He said a recent PET CT scan showed "no evidence of lymphoma".

"We've also done a bone marrow biopsy recent where we look under a microscope and look for any evidence of residual lymphoma and there was no evidence in Troy's case," Dr Scott said.

A third test, which involves looking for traces of lymphoma beyond a microscopic level, has also come back clear.

"At this point in time the results are as good as we could have ever hoped for," Dr Scott said.

Mr Daley said the results were "10 times better" than anyone could have predicted.

"Within 28 days we've had more success than we've had in five years," he said.

"We don't exactly know what the future holds but at this stage, for what I've been through I couldn't be any better."

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CAR T-cell therapy treatment helps cancer patient beat near impossible odds - ABC News

Correlation of whole-bone marrow dual-time-point (18)F-FDG, as measured by a CT-based method of PET/CT quantification, with response to treatment in…

This article was originally published here

Am J Nucl Med Mol Imaging. 2020 Oct 15;10(5):257-264. eCollection 2020.

ABSTRACT

The practical application of dual-time-point-imaging (DTPI) technique still remains controversial. One of the issues is that current parameters of DTPI quantification suffer from some deficiencies, mainly limited sampling of the diseased sites by confining measurements to specific locations. We aimed to examine the correlation between the percent change from early to delayed scans in whole-bone marrow (WBM) 18F-FDG uptake, as measured by a CT-based method of PET/CT quantification, and response to treatment in multiple myeloma (MM) patients. Pre-treatment 18F-FDG-PET/CT scans of 36 newly diagnosed MM patients were collected in a prospective study at 1 h and 3 h post tracer injection (NCT02187731). A threshold algorithm based on bone Hounsfield units on CT was applied to segment and quantify WBM 18F-FDG uptake. Patients were separated into two treatment groups: high-dose therapy with autologous stem cell transplant (HDT) and non-high dose therapy (non-HDT). The International Response Criteria for MM patients was used to determine each patients response to treatment. In the HDT group, WBM 18F-FDG uptake increased significantly in patients that had a poor response to treatment, from a median of 1.31 (IQR: 1.13-1.64) at 1 h to a median of 1.85 (1.45-2.10) at 3 h. The median percent change was 37.77% (IQR: 23.47-46.4), with a range of 6.10-50.73 (P = 0.003). However, no significant change in uptake was observed in patients with a complete response (P = 0.24). The same trend was observed for the non-HDT group. WBM uptake of 18F-FDG assessed with dual-time-point imaging may have a role in predicting treatment response in MM.

PMID:33224622 | PMC:PMC7675111

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Correlation of whole-bone marrow dual-time-point (18)F-FDG, as measured by a CT-based method of PET/CT quantification, with response to treatment in...

Late Effects of Therapy Plague Many Patients Who Survived AML as Youths, Young Adults – AJMC.com Managed Markets Network

Most people who are diagnosed with AML are middle-aged or older. The American Cancer Society estimates the average age of a patient at AML diagnosis is 68. However, a small portion of patients will develop the disease in childhood or young adulthood.

Lead author Renata Abraho, MD, MSc, PhD, of the UC Davis Comprehensive Cancer Center, and colleagues, noted that treatments for patients with AML are typically similar regardless of the patients age. Generally, patients are given anthracycline- and cytarabine-based induction therapy, and then intensive chemotherapy or hematopoietic stem cell transplantation (HSCT). The differences, however, are that central nervous system-directed therapy is often used in pediatric patients, but not in adult patients, and that adolescents and young adults (AYAs) with AML receive HSCT at a higher rate than older patients.

Abraho said those aggressive treatment decisions for younger AML patients can be a mixed blessing.

Although these therapies may result in AML cure, they also contribute to late physical and psychosocial adverse effects in survivors, Abraho and colleagues wrote.

In hopes of gaining a better understanding of those effects, the investigators identified 1,168 AYAs with AML who were placed in the California Cancer Registry between 1996 and 2012 and who had survived at least 2 years following diagnosis. Those patients were followed through the year 2014, with hospital discharge data utilized in order to quantify possible late effects of their AML treatment.

The data showed that 10 years following diagnosis, more than a quarter of patients (26%) had developed an endocrine disease; 19% had developed cardiovascular disease; and 7% had developed a respiratory disease. Other serious illnesses were also identified, though at lower rates. Patients who underwent HSCT were twice as likely to experience most of the late effects, the investigators said.

Notably, however, the authors found that non-medical factors appeared to play a role in some of the outcomes. For instance, AYA survivors of AML were more likely to experience late effects if they had lived in a poor neighborhood at the time of their diagnosis. Hispanic, black and Asian/Pacific Islander survivors also faced increased risks.

The higher risk may relate to the financial hardship that patients with cancer often experience, said UC Davis Theresa Keegan, MS, PhD, the studys senior author, in a press release. As a result of cancer, AYA survivors and their families may miss work, experience income loss and incur substantial out-of-pocket expenses.

Keegan added that factors such as therapeutic management, patient response to treatment, and high-risk mutations in AML can also lead to a higher risk of after effects.

From a physician perspective, Abraho said the study data underscore the importance of vigilance even years after a diagnosis and cure.

Our findings can help clinicians and policymakers develop better survivorship care plans to reduce suffering and death among AYA survivors of AML, she said, in the press release.

Reference:

Abraho R, Huynh JC, Benjamin DJ, et al. Chronic medical conditions and late effects after acute myeloid leukaemia in adolescents and young adults: a population-based study, International Journal of Epidemiology doi: 10.1093/ije/dyaa184

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Late Effects of Therapy Plague Many Patients Who Survived AML as Youths, Young Adults - AJMC.com Managed Markets Network