Engineered cells successfully treat cardiovascular and pulmonary disease

 Scientists at UC San Francisco have shown that gene-edited cellular therapeutics can be used to successfully treat cardiovascular and pulmonary diseases, potentially paving the way for developing less expensive cellular therapies to treat diseases for which there are currently few viable options.

The study, in mice, is the first in the emerging field of regenerative cell therapy to show that products from specially engineered induced pluripotent stem cells called "HIP" cells can successfully be employed to treat major diseases while evading the immune system. The findings subvert the immune response that is a major cause of transplant failure and poses a barrier to using engineered cells as therapy.

"We showed that immune-engineered HIP cells reliably evade immune rejection in mice with different tissue types, a situation similar to the transplantation between unrelated human individuals. This immune evasion was maintained in diseased tissue and tissue with poor blood supply without the use of any immunosuppressive drugs." said Tobias Deuse, MD, the Julien I.E. Hoffman, M.D. Endowed Chair in Cardiac Surgery and a first author of the study.

Deuse's research is an example of "living therapeutics," an emerging pillar of medicine in which treatments are broadly defined as living human and microbial cells that are selected, modified, or engineered to treat or cure disease.

The study appears in PNAS (Proceedings of the National Academy of Science).

"Universal Stem Cells" Avoid Immune Detection

The prospects of generating specialized cells in a dish that can be transplanted into patients to treat various diseases are encouraging, the scientists report. However, the immune system would immediately recognize cells that were recovered from another individual and would reject the cells. Hence, some scientists believe that custom cell therapeutics need to be generated from scratch using a blood sample from every individual patient as starting material.

The research group at UCSF followed a different approach, using gene editing to create 'universal stem cells' (named HIP cells) that are not recognized by the immune system and can be used to make "universal cell therapeutics."

The team tested the ability of these cells to treat three major diseases affecting different organ systems: Peripheral artery disease; chronic obstructive pulmonary disease from alpha1-antitrypsin deficiency; and heart failure, increasingly a global epidemic with more than 5.7 million patients in the United States alone and some 870,000 new cases annually.

The scientists transplanted specialized, immune-engineered HIP cells into mice with each of these conditions and were able to show that the cell therapeutics could alleviate peripheral artery disease in hindlimbs, prevent the development of lung disease in mice with alpha1-antitrypsin deficiency, and alleviate heart failure in mice after myocardial infarction.

To enhance the translational aspect of this proof-of-concept study, the researchers assessed the treatment's efficacy using standard parameters for human clinical trials focusing on outcome and organ function.

The Promise of an Affordable Option

Deuse, who is also surgical director of the Transcatheter Valve Program and directs Minimally Invasive Cardiac Surgery, plans to explore the potential of these universal stems cells for treating other endocrine and cardiovascular conditions. He noted that, because of the novelty of the approach, a careful and measured introduction into clinical trials will be crucial. Once more is known about human safety, he said, it will be easier to estimate when treatments using HIP cells might be approved and available for patients.

One of the great benefits of this approach, said Deuse, is that the strategy of immune engineering comes with a reasonable price tag. It would make the manufacturing of universal, high-quality cell therapeutics more cost effective, could allow future treatment of larger patient populations, and facilitate access for patients from underserved communities.

"In order for a therapeutic to have a broad impact, it needs to be affordable," said Deuse. "That's why we focus so much on immune-engineering and the development of universal cells. Once the costs come down, the access for all patients in need increases."

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Story Source:

Materials provided by University of California - San Francisco. Note: Content may be edited for style and length.

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Journal Reference:

1. Tobias Deuse, Grigol Tediashvili, Xiaomeng Hu, Alessia Gravina, Annika Tamenang, Dong Wang, Andrew Connolly, Christian Mueller, Beñat Mallavia, Mark R. Looney, Malik Alawi, Lewis L. Lanier, Sonja Schrepfer. Hypoimmune induced pluripotent stem cell–derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice. Proceedings of the National Academy of Sciences, 2021; 118 (28): e2022091118 DOI: 10.1073/pnas.2022091118

https://www.sciencedaily.com/releases/2021/07/210706115329.htm

As Delta Cases Surge, FDA Pressured to Fully Approve COVID Vaccines

 More and more experts are urging the FDA to grant full approval to the Pfizer and Moderna COVID-19 vaccines because it might jump-start the stalled national vaccination program and slow down the surge of the Delta variant infection.

The FDA granted emergency use authorization in December to those two vaccines, which are based on mRNA technology. Both companies have applied for full approval but it's unclear when the FDA will act. 

Eric Topol, a professor of molecular medicine at Scripps Research, and editor-in-chief of WebMD's sister site, Medscape, is one scientist urging full approval soon.

In a guest essay in The New York Times, he wrote that people taking a wait-and-see attitude toward the vaccine might get a shot if the FDA granted full approval. Also, people might take the step if required by their employers. 

"Some people who understand that the 'E' in 'EUA' stands for 'emergency' are waiting for full FDA approval before they receive a shot," Topol wrote. "Others may not get immunized unless their employers require it, and many organizations — including, reportedly, the military — are waiting for the vaccines to be fully approved before instituting such mandates."

Topol said the rapid spread of the Delta variant is one reason for the FDA to move more quickly.

"The agency should make full approval its number one priority, and its leadership should communicate its plans to the public," he wrote.

The CDC says 183 million doses of the Pfizer vaccine and 135 million doses of the Modern vaccine have been administered in the United States since December. Infections, hospitalizations, and deaths have dropped sharply since.

"That's as good as it gets when it comes to having data on safety and efficacy," said Céline Gounder, MD, an epidemiologist at New York's Bellevue Hospital, according to Politico.  "We have it in real life — what more can people ask for?"

But vaccine hesitancy remains. The CDC says only 55.2% of the total U.S. population has gotten at least one dose and 47.7% is fully vaccinated. The Delta variant has been recognized as the dominant strain in the United States.

In a comment to Politico, FDA spokesperson Abby Capobianco declined to offer a timeline for when the agency might grant full approval of the Pfizer and Moderna vaccines.

"Although an authorization is not an FDA approval, the FDA conducted a thorough scientific evaluation of each of the authorized vaccines and can assure the public and medical community that the vaccines meet FDA's rigorous standards for safety, effectiveness, and manufacturing quality," she said.

Politico said Pfizer and Moderna requested priority review, meaning the agency's goal would be to make a decision within 6 months of receiving the application.

Some scientists want the FDA to go slow. A group of them lodged a "Citizen Petition" with the FDA asking the agency to delay full approval, according to a blog on the website of the BMJ, formerly known as the British Medical Journal.

"The message of our petition is 'slow down and get the science right — there is no legitimate reason to hurry to grant a license to a coronavirus vaccine.' We believe the existing evidence base — both pre- and post-authorization — is simply not mature enough at this point to adequately judge whether clinical benefits outweigh the risks in all populations," the BMJ reported.

The one-shot Johnson & Johnson vaccine received emergency authorization in February, but the company has not applied for full approval yet. That vaccine does not use mRNA technology.

Delta Variant Grows Quickly Inside People, Study Says

Meanwhile, two studies showed the dangers the Delta variant poses.

Researchers at the Guangdong Provincial Center for Disease Control and Prevention in China say the Delta variant is not just highly transmissible. It also grows faster inside an infected person than other strains, according to NPR.

The scientists determined that "people infected with the Delta variant had about 1,000 times more copies of the virus in their respiratory tracts than those infected with the original strain of the coronavirus," NPR said.

The Delta variant also makes a person sicker faster, taking around 4 days to reach detectable levels inside a person, compared to 6 days with the original COVID-19 strain, NPR said.

A second study, out of France, highlighted the importance of getting two shots of two-dose vaccines like Moderna and Pfizer.

The study said one dose "barely inhibited" infection by the Delta variant, whereas two doses provided a 95% neutralizing response. The study, published in Nature, echoes previous research about how much protection vaccines offer against the Delta variant.

LA County COVID Cases Jump 165% in a Week

COVID-19 is making a comeback in Los Angeles County, also because of the Delta variant.

Los Angeles County Public Health said in a news release that there were 839 new COVID-19 cases this week, a 165% increase over last week.

The daily average case rate is now 3.5 cases per 100,000 people, compared to 1.74 cases a week ago. The daily test positivity rate on Thursday was 2.5%, up from 1.2% last week.

"Overall COVID-19 trends are going in the wrong direction for everyone, and are particularly concerning given the proliferation of the Delta variant," said Barbara Ferrer, director of public health.

The department said the Delta variant has been the most commonly sequenced variant in L.A. County since the beginning of June and "now accounts for the majority of variants of concern identified by labs."

Sources

The New York Times: "It's Time for the F.D.A. to Fully Approve the mRNA Vaccines."

Politico: "Calls mount on FDA to formally endorse Covid vaccines as Delta surges."

BMJ. "Why we petitioned the FDA to refrain from fully approving any covid-19 vaccine this year."

Virological: "Viral infection and transmission in a large well-traced outbreak caused by the Delta SARS-CoV-2 variant."

NPR: "The Delta Variant Isn't Just Hyper-Contagious. It Also Grows More Rapidly Inside You."

Nature: "Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization"

L.A. County Department of Public Health: "L.A. County Sees Increased Spread of COVID-19 and Delta Variant Cases; Fully Vaccinated People Remain Well Protected - 11 New Deaths and 839 New Confirmed Cases of COVID-19 in Los Angeles County."

https://www.medscape.com/viewarticle/954554

Healthcare mergers, 'pay for delay' deals get added scrutiny under Biden order

 

• President Joe Biden on Friday announce he would call on the Department of Justice and Federal Trade Commission "to enforce the antitrust laws vigorously" in healthcare and other key industries. The White House said it's urging antitrust regulators to recognize that "the law allows them to challenge prior bad mergers that past Administrations did not previously challenge."
• The executive order instructs antitrust regulators to "review and revise" their merger guidelines to ensure patients are not harmed by a potential tie-up.
• The order also tackles prescription drugs, calling on regulators to ban "pay for delay" arrangements, and instructs the FDA to work with states to import drugs from Canada.

Consolidation in healthcare is a persistent issue as mergers and acquisitions have continued at a steady clip for years, with a slew of research finding the unions lead to higher prices.

Biden's executive order notes that lack of competition in the healthcare market can lead to price increases without improving quality of care.

"Thanks to unchecked mergers, the ten largest healthcare systems now control a quarter of the market," the release from the White House said, citing research from Deloitte.

So far this year, there have been 27 health system mergers and acquisitions, representing total revenue of $17.2 billion. Although the number of deals are below last year's levels, the deals are larger, according to the latest report from consultancy Kaufman Hall.

Although the executive order calls on regulators to make the healthcare industry a priority, the FTC has signaled it is already doing so in various ways.

Last year, the FTC said it was expanding its retrospective merger review program to consider and research new areas of study that could ultimately help the agency police future deals. The agency followed up, earlier this month, by signaling it is prioritizing healthcare as part of its enforcement strategy over the next decade. After a vote of the commissioners, the agency agreed to focus on a number of key sectors, including technology companies and healthcare, which includes hospitals, pharmacy benefit managers and pharmaceutical companies.

The​ executive order also directs the U.S. Department of Health and Human Services to finish implementing rules on the surprise billing ban, continue to support price transparency efforts and standardize health plans on the Affordable Care Act marketplace to make it easier to comparison shop.

The price transparency rule requiring hospitals to publish some of the rates they negotiate with insurance companies went into effect at the beginning of this year, but various reviews have found most hospitals are not complying in full. The penalty for noncompliance is $300 a day, which researchers have said may be too low give the requirement teeth.

https://www.biopharmadive.com/news/healthcare-mergers-pay-for-delay-deals-get-added-scrutiny-under-biden-or/603115/

Sigilon Therapeutics Shares Lower After Clinical Hold on Hemophilia Study

 Shares of biotechnology company Sigilon Therapeutics Inc. touched a 52-week low Friday after the company said the U.S. Food and Drug Administration placed its Phase 1/2 study of SIG-001 in patients with severe or moderately severe hemophilia A on clinical hold.

Sigilon said the hold was initiated after it submitted a serious adverse event and temporary enrollment halt to the FDA and other agencies.

At 1:05 p.m. ET, the company's shares were trading 24% lower at $7.06. Volume at the time topped 1.4 million shares. The stock's 65-day average volume is 159,069.

Earlier in the session, the shares touched a 52-week low of $6.28.

The company said one of three patients dosed with SIG-001 developed inhibitors to Factor VIII. The patient is responding well to medical treatment and his condition continues to improve, it said.

"Patient safety is our top priority, and we are encouraged that the patient is recovering," said Rogerio Vivaldi, the company's president and chief executive. "In collaboration with the regulatory agencies and our advisors, we are conducting a thorough investigation of this event to confirm whether there was a causal relationship between the development of inhibitors and SIG-001. We are committed to working with the FDA to resolve the clinical hold."

https://www.marketscreener.com/quote/stock/SIGILON-THERAPEUTICS-INC-116081124/news/Sigilon-Therapeutics-Shares-Lower-After-Clinical-Hold-on-Hemophilia-Study-35829612/

EU delivers enough doses to vaccinate 70% adults: von der Leyen

 The European Union (EU) has delivered enough coronavirus vaccine doses to member states to vaccinate at least 70% of adults, European Commission chief Ursula von der Leyen said in a statement.

Von der Leyen urged the EU countries to increase vaccinations and said that about 500 million doses would be distributed across the union by Sunday.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-nbsp-EU-delivers-enough-doses-to-vaccinate-70-adults-von-der-Leyen-says-35831160/

Intraocular lens platform provider RxSight files for a $100 million IPO

 RxSight, a commercial-stage provider of an intraocular lens that can be adjusted after cataract surgery, filed on Friday with the SEC to raise up to $100 million in an initial public offering.

RxSight markets its RxSight Light Adjustable Lens system, comprised of the RxSight Light Adjustable Lens and the RxSight Light Delivery Device, to offers the first and only commercially available intraocular lens technology that enables doctors to customize and optimize visual acuity for patients after cataract surgery.

The Aliso Viejo, CA-based company was founded in 1997 and booked $15 million in sales for the 12 months ended March 31, 2021. It plans to list on the Nasdaq under the symbol RXST. J.P. Morgan, BofA Securities, SVB Leerink, Wells Fargo Securities, and BTIG are the joint bookrunners on the deal. No pricing terms were disclosed.

Relevant Profile: RXST

https://www.renaissancecapital.com/IPO-Center/News/83856/Intraocular-lens-platform-provider-RxSight-files-for-a-$100-million-IPO

Gene therapy biotech Omega Therapeutics files for a $100 million IPO

 Omega Therapeutics, a preclinical biotech developing gene therapies for cancer and other diseases, filed on Friday with the SEC to raise up to $100 million in an initial public offering.

Omega Therapeutics aims to use its proprietary OMEGA Epigenomic Programming platform to pioneer a new class of DNA-sequence-targeting, mRNA-encoded therapeutics. Its pipeline consists of preclinical programs that span regenerative medicine, multigenic diseases including immunology, oncology, and select monogenic diseases. The company has conducted in vivo preclinical studies in hepatocellular carcinoma, non-small cell lung cancer, and acute respiratory distress syndrome.

The Cambridge, MA-based company was founded in 2016 and plans to list on the Nasdaq under the symbol OMGA. Omega Therapeutics filed confidentially on May 10, 2021. Goldman Sachs, Jefferies, Piper Sandler, and Wedbush PacGrow are the joint bookrunners on the deal. No pricing terms were disclosed.

Relevant Profile: OMGA

https://www.renaissancecapital.com/IPO-Center/News/83859/Gene-therapy-biotech-Omega-Therapeutics-files-for-a-$100-million-IPO