By: New York Times | Published: April 2, 2020 10:59:26 pm On Saturday, the FDA took the unusual step of approving those drugs to treat hospitalized patients with coronavirus on an emergency basis, even though no significant clinical trials have yet been done.

Written by Katie Thomas

An experimental stem cell therapy derived from human placentas will begin early testing in patients with the coronavirus, a New Jersey biotech company said Thursday.

The treatment, being developed by the company Celularity, has not yet been used on any patients with symptoms of COVID-19, but it has caught the attention of Rudy Giuliani, President Donald Trumps personal lawyer. Giuliani recently featured an interview with the company founder on his website and said on Twitter that the product has real potential, while also criticizing the Food and Drug Administration for not moving more quickly to approve potential remedies.

There is no proven treatment for the respiratory disease, but several experimental approaches, including old malaria drugs and HIV antivirals, are being tested in patients around the world.

READ | Video from Japan shows how COVID-19 is getting transmitted through a third route

Celularity has also enthusiastically publicized the news of its early-stage trial for its treatment, known as CYNK-001. In an email Wednesday to a reporter, its public relations firm described a development as the first FDA approval for COVID-19 cell therapy. The agencys decision, however, merely gives a green light for its product to be used in a clinical trial, not widely prescribed to patients.

In recent weeks, the established scientific process of evaluating a drugs safety and effectiveness has been upended by Trump, who has repeatedly promoted the potential of two long-used malaria drugs that have shown mainly anecdotal evidence of helping patients. On Saturday, the FDA took the unusual step of approving those drugs to treat hospitalized patients with coronavirus on an emergency basis, even though no significant clinical trials have yet been done.

The early trial by Celularity which will primarily evaluate safety, as well as an initial look at efficacy will test its therapy in up to 86 patients with symptoms. They will receive infusions of the cell therapy in the hopes it will prevent them from developing the more severe form of the disease, Dr. Robert Hariri, Celularitys founder and chief executive, said in an interview Wednesday.

The objective here is preventative, Hariri said. If the timing of giving this can prevent those patients who have early disease from progressing to the more serious, life-threatening form, it could be a very, very useful tool.

The therapy involves using stem cells from the placenta known as natural killer cells that help protect a developing fetus or newborn from viruses that have infected the mother. Celularity has been testing these cells in cancer patients.

Hariri said the trial, which would not include a placebo control group, will take place at academic medical centers around the country. He said the company expected to see initial results about 30-60 days after the first patients receive their dose. If this study is successful, Hariri said, the company would move to a placebo-controlled study that would evaluate the drugs efficacy against the disease.

At least one outside expert said the approach could present safety risks. Paul Knoepfler, a stem cell researcher at the University of California, Davis, said that patients with coronavirus can develop severe reactions where their immune systems go too far in attacking cells in their lungs, causing damaging inflammation. Other cell therapies tested in China are designed to dampen the immune response. He said one risk with the natural killer cells is they could go in the other direction, exacerbating respiratory problems by massive killing of the patients respiratory cells.

Despite the scant evidence, Giuliani has become an early booster, interviewing Hariri on a podcast published on his website Saturday and praising the treatment on Twitter, saying, this therapy has real potential. In a tweet Saturday, he added, Lets hope FDA can recognize that their cumbersome process designed to keep us safer, if it is not altered dramatically in times of great need, can result in unimaginable loss of human life.

Around the same time, Twitter deleted a post by Giuliani that it said violated its rules. The tweet, from March 27, made unfounded claims about the malaria drug hydroxychloroquine, one of the treatments that Trump has supported.

Hariri said that he has known Giuliani for years and that the appearance on his podcast was a friendly chat between people who know each other and who share a common interest in this particular response to this disease.

He said that he has no business relationship with Giuliani, and that Giuliani is not representing him in any way, either paid or unpaid.

I dont have anything to do with what the mayor tweets or whatnot, and I dont agree or disagree with anything, he said.

Hariri said the company would follow the established process for testing whether a drug works.

We have waited for the FDA to complete their review, which they did in a heroic and quick fashion, he said.

On Wednesday evening the same day the FDA approved his trial Hariri praised the appearance by the agencys commissioner, Dr. Stephen Hahn, on the conservative Fox News talk show The Ingraham Angle.

We are fortunate to have Dr. Hahn at the helm, he tweeted.

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Unproven Stem Cell Therapy Gets OK for Testing in Coronavirus Patients - The Indian Express

OTTAWA, March 31, 2020 (GLOBE NEWSWIRE) -- In recent weeks, a number of claims have been made that stem cells can be used as a treatment for the coronavirus disease (COVID-19). Globally, there is no clinically tested and government approved stem cell-based treatment for COVID-19.

The Stem Cell Network (SCN) urges extreme caution to those who are considering purchasing products or services advertised as a preventative or curative treatment for COVID-19. In alignment with other international stem cell and regenerative medicine organizations, SCN strongly opposes the marketing of unproven therapies and urge consumers and patients to consult with their doctor or specialist if they have questions or concerns about their health. The best way to combat the spread COVID-19 is to follow the careful advice given by Canada's Chief Public Health Officer.

Researchers across the globe are collaborating and working hard to find legitimate treatments for COVID-19, but this will take time. It is important to note that when a treatment does become available, it will be announced through recognized medical authorities, such as the World Health Organization, which is coordinating global efforts and actively compiling a database of published research on COVID-19.

For the most up-to-date information on COVID-19, please consult:World Health OrganizationPublic Health Agency of Canada

To learn more about clinical trials or stem cells:Stem Cell Network Clinical Trial FAQsCloser Look at Stem Cells

About the Stem Cell NetworkTomorrow's health is here. The Stem Cell Network (SCN) is a national non-profit that supports stem cell and regenerative medicine research, training the next generation of highly qualified personnel, and delivering outreach activities across Canada. SCN's goal is to advance science from the lab to the clinic for the benefit of Canadians. SCN has been supported by the Government of Canada since inception in 2001. This strategic funding, valued at $118M has benefitted approximately 170 world-class research groups and 3,000 trainees and has catalyzed 23 clinical trials. stemcellnetwork.ca

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Stem Cell Network Warns that Claims of Stem Cell Treatments for COVID-19 Are Unfounded and Misleading - Benzinga

Maggie L. Shaw

Mantle cell lymphoma is a type of B-cell non-Hodgkin lymphoma with a typically poor prognosis. Even with an allogeneic stem cell transplant, patients can become resistant to chemotherapy. Most do not survive 4 or 5 years after diagnosis, and the 10-year survival rate hovers between 5% and 10%.

Chimeric antigen receptor (CAR) T-cell therapy has been making great inroads as targeted treatment for many types of cancers highly resistant to other treatments, by prolonging patient survival and increasing their quality of life. Until now, similar results have not been seen in patients with MCL. However, with their successful phase 2 ZUMA-2 trial results just published in the New England Journal of Medicine, a group of researchers led by Michael Wang, MD, from The University of Texas MD Anderson Cancer Center, are able to show that these patients can benefit from the specialized therapy.

In this study conducted in the United States and Europe, the patient population had relapsed/refractory progressive disease despite receiving Brutons tyrosine kinase (BTK) inhibitor therapy and from 3 to 5 prior therapies.

BTK inhibitor therapy has greatly improved outcomes in patients with relapsed or refractory mantle cell lymphoma, yet patients who have disease progression after receiving the treatment are likely to have poor outcomes, with median overall survival of just 6 to 10 months, the authors said.

The median patient age was 65 years (range, 38-79). They were evaluated for response to a single infusion of KTE-X19, an anti-CD19 CAR T-cell therapy, that was dosed at 2106 CAR T cells/kg of body weight. Seventy-four patients were enrolled between October 24, 2016, and April 16, 2019; the treatment was manufactured for 71 and ultimately administered to 68.

There was a follow-up after 60 patients were monitored for 7 months, at which time a primary efficacy analysis was conducted. The primary endpoint was objective response (complete [CR] or partial [PR]), which was confirmed via bone marrow evaluation and positron emission tomography-computed tomography.

Overall, 85% of the entire study cohort of 74 patients was able to reach an objective response to KTE-X19, 59% of whom had a CR. These numbers were even higher among the group of 60 patients. Ninety-three percent (95% CI, 84%-98%) achieved an objective response, which was evaluated by an independent radiologic review committee. And of this group, 67% (95% CI, 53%-78%) had a CR.

The median times to response were impressive, with there being 1 month (range, 0.8-3.1) to initial response and 3 months (range, 0.9-9.3) to CR. In addition, of the 42 patients who initially had a PR or stable disease (SD), 24 (21 who had a PR, 3 who had SD) progressed to a CR in a median 2.2 months (range, 1.8-8.3).

Progression-free (PFS) and overall survival (OS) results also show promise to treatment with KTE-X19. As of the data cutoff date, there was evidence of remission in 78% patients who had a CR, with similar results seen in 57% of patients from the primary efficacy analysis. Overall, at 12 months, the PFS and OS were 61% and 83%, respectively.

Common adverse events to the treatment of grade 3 or higher included cytopenias (94%) and infections (32%). Ninety-one percent also experienced cytokine release syndrome, with a median time to onset of 2 days (range, 1-13) for any grade and 4 days (range, 1-9) for at least grade 3, but none died as a result. According to the study authors, most symptoms were reversible.

ZUMA-2 is the first multi-center, phase 2 study of CAR T-cell therapy for relapsed/refractory mantle cell lymphoma, and these efficacy and safety results are encouraging, stated Wang. Although this study continues, our reported results, including a manageable safety profile, point to this therapy as an effective and viable option for patients with relapsed or refractory mantle cell lymphoma.

Reference

Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-Cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382;1331-1342. doi: 10.1056/NEJM0a1914347.

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Is There a New CAR T-Cell Treatment for Mantle Cell Lymphoma? - AJMC.com Managed Markets Network

Dive Brief:

First-generation autologous CAR-T therapies involve genetically edited immune cells taken directly from patients in a lengthy, logistically challenging and costly procedure. Fate is one of a group of companies advancing an "off-the-shelf" cell therapy approach, which utilizes cells taken from healthy donors.

It's an emerging field of research that's still in its early stages. Only slivers of human data have been published thus far. These companies have yet to prove off-the-shelf approaches can match, or surpass, what has been seen with CAR-T without triggering serious or potentially deadly immune reactions.

But pharma has made notable investments in the work, which could lead to treatments that are quicker and less costly to produce than their autologous counterparts. Among them: Pfizer's wide-ranging deal with Allogene Therapeutics in 2018 as well as Bayer's buyout of BlueRock Therapeutics and investment in Century Therapeutics last year.

Entering this year, the allogeneic field looked set to take some steps forward. As analyst firm Jefferies noted in March, Precision,AllogeneTherapeutics and CRISPRTherapeutics, which each use different off-the-shelf approaches, could all produce notable human data this year.

The coronavirus pandemic, however, has threatened clinical research timelines across the industry, disrupting study enrollment and treatment.

Fate is in the mix, too, though it acknowledged COVID-19 could impact its plans. In announcing the J&J deal, Fate also warned of coronavirus-related "delays or disruptions in patient enrollment and site initiation" that will affect the timing of its clinical trials. It didn't provide specific details.

The J&J partnership does give Fate some breathing room. The San Diego biotech is getting $100 million to produce up to four new therapies that J&J will have the option to license, while J&J covers the associated R&D costs. Fate could receive another $3 billion in various conditional payments tied to regulatory and sales milestones if all goes to plan, though those payments may never materialize.

"From speaking to management, we think this is exactly the type of deal [Fate] was looking for," wrote Cantor Fitzgerald analyst Alethia Young, referring to a back-loaded agreement that gives the company the chance to keep some rights to the programs in the alliance.

Young wrote the deal is also "a strong validation" of Fate's approach, which draws from stem cell and CAR-T technologies.Fate turns cells from donors into induced pluripotent stem cells, which in turn can be re-engineered into a variety of different cells. In their partnership, for instance, Fate and J&J aim to create certain types of immune cells natural killer, or NK cells, and T cells that can hunt down tumors.

The partnership doesn't include any of the other treatments currently in Fate's pipeline. Shares climbed about 20%, to around $25 apiece, in pre-market trading Friday.

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Fate inks $100M J&J pact for 'off-the-shelf' cancer cell therapies - BioPharma Dive

Parker Hannifin has sponsored this post.

Cell therapies promise treatments for serious illnesses, but require automation and manufacturing expertise to scale up production for research and products. (Image courtesy of Parker Hannifin.)

Cellular therapies and bio-fabrication are two of the most revolutionary treatments for serious illnesses to be developed in the early 21st century, offering the hope of cures where once only symptomatic treatments were available. The 2006 discovery of Induced Pluripotent Stem Cells (iPSCs) formed a catalyst for research and development into these new therapeutic approaches. Stem cell therapies offer promising avenues for the treatment of devastating illnesses such as diabetes, cancer, heart disease and even neurological diseases.

Tailored cell therapies using iPSCs are considered to be the new Third Pillar of the drug and treatment industry, standing alongside small molecules and biologics as tools for treatment. However, the widespread research and treatment using cell therapies requires mass-produced iPSCs to be available in quantitywhich means advanced manufacturing techniques.

Cells are tiny living, complex organisms; they must be handled with precision and accuracy. Automated handling equipment needs a heightened level of dexterity and control. (Image courtesy of Parker Hannifin.)

Scaling up the production of iPSCs requires investmentsome of which is already in place with two deals: $70 million to the New Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) to advance U.S. leadership in the biopharmaceutical industry, and an 87-member coalition funded by the Defense Department called ARMI-BioFab USA, which aims to develop the next-generation techniques needed to repair and replace cells, tissues and organs for wounded military service veterans.

The key to success in the scale-up of production is advanced automation, which will improve the manufacturing process used to fabricate cell colonies.

Currently, most research and cell fabrication involves a significant amount of manual work and decision-making, which can be error-prone and represents a bottleneck in attempts to scale these fabrication processes.

One way to improve the manufacturing processes related to cell therapies is by partnering with experienced automation and manufacturing industry leaders, who can share their expertise. An example of this is the partnership between Parker Hannifin and CellX Technologies. Together, these companies have developed a platform to help researchers and clinicians quantify key morphological stem cells, automate the handling process and perform cell maintenance.

Current cell therapy research is hampered by difficulties with a lack of large field-of-view and high-resolution optics when imaging live cell cultures. This makes it difficult to monitor and quantify changes to the cells. Available devices and equipment for sampling, transfer or deletion of specific cells or colonies also lack the rigorous accuracy that manufacturing-scale production would require. Instead, visual assessment and manual transfer by lab technicians is the usual methodsacrificing speed and production volume.

An automated, image-based system would enable accurate quantitative metrics of biological performance and will be applicable at a cell-by-cell or a colony-by-colony basis, among other benefits.

Automated cell-handling equipment needs to be precise and finely calibrated in order to handle delicate cells with the necessary dexterity and control. Three primary handling techniques are used for this very difficult automation task:

Combining capabilities for these three functions into a single platform will enable multiple benefits, including improved reproducibility and quality of cells for research and products, reduce variability and costs from manual processes, improved lot traceability and documentation, and define quantitative process quality attributes and metrics.

Parker Hannifins expertise in manufacturability, digital pathology and additive manufacturing lends itself directly to the development of the CellX platform. CellX enables automation of the scanning and identification processes, and pairs this with cell selection and precision placement.

The CellX Device, developed by Parker Hannifin and CellX Technologies, combines large field-of-view imaging with precision instrumentation, fluidics, and documentation and control capabilities. (Image courtesy of Parker Hannifin.)

CellX also needed customization of standard products. Parker Hannifin has decades of experience in close tolerance special purpose fluidics and actuator technology, and developed enabling technology for the CellX central core, which consists of a high-quality automated inverted microscope and CCD camera with brightfield and fluorescent imaging capabilities.

Some of the specialized equipment that Parker Hannifin helped develop for CellX includes a load and removal station for disposable cell-picking tips, and environmentally controlled workspace to maintain sterility and oxygen levels, and an integrated sensor to accurately locate each new tip.

The combined precision and imaging capabilities of the CellX platform enable rapid data collection and high repeatability, which means researchers can rely on accurate data, healthy cell colonies and quantitative, reproducible standards for cell therapy development. Parker Hannifin has a proven history of developing new tools and instruments for manufacturing processes with their partner OEMsand in the case of CellX, accelerating the development of the future of cell therapies.

To learn more about Parker Hannifins development of the CellX platform, including use cases and details on the full complement of customized equipment and enabling features, download the full whitepaper from Parker Hannifin.

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Cell Therapies Can Revolutionize Treatment, Automation Needed to Scale Production - ENGINEERING.com