Stem Cell Clinic

Potential Risks of Treatment with Unapproved Regenerative Medicine Products – FDA.gov

By: Peter Marks, M.D., Ph.D., Director, Center for Biologics Evaluation and Research

Protecting patients is at the core of what we do at the U.S. Food and Drug Administration. Now the FDA is providing additional resources to help consumers understand the risks associated with unapproved stem cell, exosome, and other products marketed as regenerative medicine products. The agency is also facilitating the reporting of side effects that may occur after their use. The FDAs receipt of this information is important to developing a better understanding of the risks associated with these products and to helping the agency identify those clinics and manufacturers putting patients at risk.

Several times in recent years, the FDA warned consumers who have been treated with, or who are considering use of, unapproved stem cell, exosome, or other products marketed as regenerative medicine products, about their potential risk. These illegal products are often marketed by clinics under the umbrella term of regenerative medicine as being safe and effective for treatment of a wide range of diseases or conditions (e.g., Alzheimers disease and other neurologic disorders, orthopedic conditions), even though they have not been adequately studied in clinical trials. And more recently, some of these clinics have been marketing or distributing their unproven products to treat complications related to COVID-19 claims that are not based on adequate clinical data.

Consumers may also have been told by clinics and health care providers that because some of these products are made from their own cells, the FDA does not need to review or approve the treatment. That is simply not true. Further, claims that a clinics FDA registration or inspection equates to FDA approval or a form of FDA endorsement, or that listing a clinical study on clinicaltrials.gov means that it has been reviewed and allowed to proceed by the FDA, are also false.

It is of utmost concern that unapproved regenerative medicine products that have no proven clinical benefit and that may cause serious harm are marketed to patients. Using these products may lead to delays in getting a proper diagnosis and could also discourage patients suffering from serious illnesses from receiving safe and effective treatments that may be available. Whats also concerning is that we know that because these products are not FDA-approved, its very likely that adverse events are underreported by health care providers who treat patients with these products, and by patients who may have been harmed. We therefore strongly encourage patients and their family members to ask questions before receiving these types of products has the product been approved by the FDA? Has the product been approved for this use? Is the product being studied in a clinical trial that has been reviewed and allowed to proceed by the FDA? Am I being charged for an unapproved product?

We encourage patients and their health care providers to report to the FDA any potential adverse events and complaints related to the use of these products using the FDAs MedWatch Adverse Event Reporting program. Stem cell, exosome, or other products marketed as regenerative medicine products may have the potential to treat many medical conditions and diseases. But for almost all these products, it is not yet known whether each product has any benefit or if the product is safe to use. We want to make sure patients understand these potential risks in order to protect themselves from being treated with and paying for an unproven and illegally marketed products. The FDA has posted a webpage for consumers that provides information about products marketed as stem cells, exosomes or other regenerative medicine products, including the conditions for which they are approved, and which products are not approved at all. The webpage also provides information on how to submit information about adverse events to the FDAs MedWatch Adverse Event Reporting Program.

Unfortunately, weve found numerous instances of products being marketed to patients without FDA approval, as well as products being manufactured with significant deviations from current good tissue practice (CGTP) and/or current good manufacturing practice (CGMP) requirements. These violations have included deficient donor eligibility practices, and inadequate aseptic practices to prevent product contamination violations that have the potential to place patients at risk. Patients have been harmed after being administered some of these violative products.

We encourage consumers who are considering treatment with regenerative medicine products to work with their health care providers to learn about the treatment being offered, and to visit our webpage. It is important to ask questions and understand the potential risks of treatment with unapproved products. The FDA will continue to work with the manufacturers of these products to support their development. But we will also continue to take appropriate action against those who put patients in harms way.

Additional Resources:

Here is the original post:
Potential Risks of Treatment with Unapproved Regenerative Medicine Products - FDA.gov

GV’s David Schenkein comes in to help mentor and bankroll a gene therapy 2.0 player, intrigued by their ‘science heavy’ approach to conquering…

One of the leading programs for a new coronavirus vaccine was championed today as investigators from Oxford and AstraZeneca spelled out a dual hit with neutralizing antibodies as well as a surge in specific T cells targeted against the virus.

According to the study:

Humoral responses to SARS-CoV-2 spike protein peaked by day 28 postprime and cellular responses were induced in all participants byday 14. Neutralising antibodies were induced in all participants after a second vaccine dose. After two doses, potent cellular and humoral immunogenicity was present in all participants studied.

The results largely confirm what was already previewed: One dose was sufficient to elicit some antibody response in over 90% of people, and a second dose pushed it to 100%, at levels similar to whats observed in convalescent patients. Spike-specific effectors T cells were observed as early as day 7, peaking at day 14 and maintained up to day 56 as expected with adenoviral vectors.

In a media briefing, AstraZeneca biopharma R&D head Mene Pangalos noted that the ongoing Phase III trials will almost certainly be testing two doses, as it would be the safest approach to making sure we hit efficacy. Lower doses can then be worked out in the future.

Unlock this story instantly and join 85,500+ biopharma pros reading Endpoints daily and it's free.

SUBSCRIBE SIGN IN

Continue reading here:
GV's David Schenkein comes in to help mentor and bankroll a gene therapy 2.0 player, intrigued by their 'science heavy' approach to conquering...

2 immunotherapies merged into single, more effective treatment – Washington University School of Medicine in St. Louis

Visit the News Hub

Mouse study suggests strategy may work against variety of cancers

Researchers at Washington University School of Medicine in St. Louis have combined two types of immunotherapy into a single treatment that may be more effective and possibly safer than current immunotherapies for blood cancers. Shown is a type of immune cell called a memory-like natural killer cell (right) attacking a leukemia cell (left). In the new study, the researchers modified the natural killer cells to help them find the leukemia cells more effectively.

Some of the most promising advances in cancer treatment have centered on immunotherapies that rev up a patients immune system to attack cancer. But immunotherapies dont work in all patients, and researchers have been searching for ways to increase their effectiveness.

Now, researchers at Washington University School of Medicine in St. Louis have combined two immunotherapy strategies into a single therapy and found, in studies in human cells and in mice, that the two together are more effective than either alone in treating certain blood cancers, such as leukemia. Evidence also suggests that the new approach could be safer than one of the most recent cellular immunotherapies to be approved by the FDA, called CAR-T cell therapy, in which the immune systems T cells are engineered to target tumor cells. Cell-based immunotherapies are most commonly used against blood cancers but can be harnessed against some solid tumors as well, such as prostate and lung tumors and melanoma.

The study appears online in the journal Blood.

In the new research, the scientists have harnessed the technology used to engineer CAR-T cells and, instead of modifying specialized immune cells called T cells, they have used similar technology to alter different immune cells called natural killer (NK) cells. The resulting immunotherapy combines the benefits of both strategies and may reduce the side effects that are sometimes seen in CAR-T cell therapy. In some patients, for example, CAR-T cell therapy causes a cytokine storm, a life-threatening overreaction of the immune system.

Immunotherapies show great promise for cancer therapy, but we need to make them more effective and more safe for more patients, said co-senior author Todd A. Fehniger, MD, PhD, a professor of medicine. This combined approach builds on the treatment strategy that we developed for leukemia patients using natural killer cells. We can supercharge natural killer cells to enhance their ability to attack cancer cells. And at the same time, we can use the genetic engineering approaches of CAR cell therapy to direct the natural killer cells to a tumor target that would normally be overlooked by NK cells. It fundamentally changes the types of cancer that NK cells could be used to treat, both additional blood cancers and potentially solid tumors as well.

In past work, Fehniger and his colleagues showed that they could collect a patients own NK cells, expose the cells to a specific recipe of chemical signals that prime the cells to attack tumors, and then return the primed cells to patients for therapy. This chemical exposure is a sort of basic training for the cells, according to the investigators, preparing the NK cells to fight the cancer. When the cells are then returned to the body, they remember their training, so to speak, and are more effective at targeting the tumor cells. Because their training has given the NK cells a memory of what to do when they encounter tumor cells, the researchers dubbed them memory-like NK cells.

In small clinical trials conducted at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, such cells were effective in putting some patients with leukemia into a lasting remission, but they didnt work for everyone. Some tumor cells still evaded the memory-like NK cells, despite the cells basic training. To help the cells find the tumor cells, so their basic training can kick in and kill the correct target, the researchers modified the memory-like NK cells with the same CAR (chimeric antigen receptor) molecule that is typically used to target T cells to tumor cells. The CAR molecule is flexible and can be modified to direct the cells to different tumor types, depending on the proteins on the surfaces of the cancer cells.

The resulting hybrid cells were more effective in treating mice with leukemia than memory-like NK cells alone, leading to longer survival for mice treated with CAR memory-like NK cells. The researchers also found the therapy to be effective despite the fact that the mice were given relatively low doses of the cells.

One aspect of this study I find most exciting is how nicely these hybrid NK cells expand in the mice to respond to their tumors, said co-senior author Melissa Berrien-Elliott, PhD, an instructor in medicine. We can provide a tiny dose and see an incredible amount of tumor control. To me, this highlights the potency of these cells, as well as their potential to expand once in the body, which is critical for translating these findings to the clinic.

Fehniger also pointed out that an advantage of NK cells in general and for biological reasons that the scientists are still working to understand NK cells dont trigger a dangerous immune response or the long-term side effects that T-cell therapy can cause in attacking the patients healthy tissues, a condition called graft-versus-host disease.

In all of the clinical trials exploring any type of NK cells, we dont see the troublesome side effects of cytokine release syndrome or neurotoxicity that we see with CAR-T cells that can profoundly affect patients, Fehniger said. These side effects can be life-threatening and require intensive care. Were still working to understand how NK cells are different. But if you can get the benefits of CAR-T cells with few if any of the side effects, thats a reasonable line of research to pursue. Another benefit of this safer therapy is the potential to give these cells to patients at an earlier stage in their disease, rather than using them as a last resort.

Other groups have developed CAR-NK cells, but a major difference is that other groups NK cells came from donated cord blood or induced stem cells, rather than adult donors or the patients themselves.

The other groups have artificially differentiated stem cells into something that resembles an NK cell, Fehniger said. With that strategy, theres no guarantee that those cells will have all the properties of typical mature NK cells. In contrast, were starting with adult NK cells, so were more confident that they will have all the inherent properties and behavior of adult NK cells, which we have already shown to be effective in certain types of cancer patients, especially those with leukemia. Inducing memory properties adds to their persistence and effectiveness against many cancer types.

Over the next several years, we would like to be able to scale up this process to produce enough cells for a first-in-human clinical trial, and investigate their effectiveness in different types of human blood cancers, he said.

This work was supported by the Howard Hughes Medical Institute; the National Institutes of Health (NIH), grant numbers F32CA200253, T32HL00708843, K12CA167540 and R01CA205239; and a NIH SPORE in Leukemia, grant number P50CA171063. Additional funding was provided by the Siteman Cancer Center through NIH grant number P30CA091842; the Leukemia and Lymphoma Society; the V Foundation for Cancer Research; the Childrens Discovery Institute at Washington University School of Medicine; the Jamie Erin Follicular Lymphoma Research Fund; and the Steinback Fund.

Berrien-Elliott and Fehniger are inventors on patents related to this study that have been filed by Washington University. Fehniger has received research support from ImmunityBio, Compass Therapeutics, and HCW Biologics, and advises Kiadis, Nkarta, Indapta, and Orca Biosystems. Other authors report serving as a consultant for Kiowa Hakka Kirin and C4 Therapeutics; receiving research funding from Bristol Myers-Squibb, Verastem Pharmaceuticals, Innate Pharmaceuticals, Genentech/Roche, Celgene, and Corvus Pharmaceuticals; having direct ownership of equity in and a consultancy with Wugen; serving on the consulting/advisory committee for Rivervest, Bioline, Amphivena and Bluebird, Celegene, Incyte, NeoImuneTech, and Macrogenics and ownership investment in Magenta and WUGEN.

Gang M, Marin ND, Wong P, Neal CC, Marsala L, Foster M, Schappe T, Meng W, Tran J, Schaettler M, Davila M, Gao F, Cashen AF, Bartlett NL, Mehta-Shah N, Kahl BS, Kim MY, Cooper ML, DiPersio JF, Berrien-Elliott MM, Fehniger TA. CAR-modified memory-like NK cells exhibit potent responses to NK-resistant lymphomas. Blood. July 2, 2020.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

Here is the original post:
2 immunotherapies merged into single, more effective treatment - Washington University School of Medicine in St. Louis

Can fully shutting down the estrogen receptor make a difference in breast cancer? Olema scores $54M to find out in the clinic – Endpoints News

From tamoxifen to aromatase inhibitors to fulvestrant, theres been no lack of endocrine treatments targeted at estrogen receptor-positive breast cancer. But Olema Oncology believes theres room for more.

The San Francisco-based biotech has convinced investors to pour in $54 million to prove it.

We saw the need for a drug that could more fully shut down the estrogen receptor, Cyrus Harmon told Endpoints News. We call it a complete estrogen antagonist to distinguish from other compounds.

After iterating through multiple generations of candidates for more than a decade funded by the founders themselves, angel investors and a now-defunct pharma collaboration Olema closed its first venture round in 2018 from BVF Partners.

BVF returned to co-lead the Series B alongside Logos Capital and Janus Henderson Investors, while new investors Cormorant Asset Management, RA Capital Management, Wellington Management Company, Surveyor Capital, Venrock Healthcare Capital Partners, and Foresite Capital joined.

We were attracted to Olema by its excellent science, robust preclinical data, experienced management team, and potential to make a significant impact on what remains a large unmet need among patients with breast and other hormone-positive cancers, Gorjan Hrustanovic, principal at BVF Partners, said.

The new cash will bankroll the program Phase I/II for OP-1250, evaluating the oral pill as a single agent for patients with ER+, HER2- who have seen their cancer come back despite treatment.

If the drug does what Olema wants it to do in the first-in-human testing, the next step will be to study it as a potential backbone therapy in combinations with others.

Thereve been a number of targeted therapies for breast cancer that have been developed in the last decade or so, such as the CDK4/6 inhibitors and PI3 kinase alpha inhibitors, Harmon said.

Whereas endocrine therapy was originally always used just by itself, it appears to pair well with these new classes of drugs.

That would require more money and likely a larger team than the current 12 to run bigger studies perhaps even an IPO that Harmon says is too early to discuss. But first, they need to get into the clinic.

One step at a time, he said.

Read the original here:
Can fully shutting down the estrogen receptor make a difference in breast cancer? Olema scores $54M to find out in the clinic - Endpoints News