Gracell Biotechnologies Inc. announced the early results of a first-in-human clinical study of GC502, an allogeneic CD19/CD7 dual-directed chimeric antigen receptor (CAR) T cell therapy for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Gracell will share the data in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2022 on April 12, 2022. GC502 leverages the novel dual-directed CAR design of Gracell's proprietary TruUCAR platform, designed to generate high-quality allogeneic CAR-T cell therapies that can be administered off-the-shelf at low cost and with fast patient's access. TruUCAR-enabled GC502 utilizes the dual-directed CAR design with one CAR targeting CD19 on malignant cells and a second CAR targeting CD7 to suppress host-versus-graft rejection. An enhancer molecule is embedded in the basic construct of TruUCAR to enhance proliferation of TruUCAR T cells. Between September 2021 and January 2022, four r/r B-ALL patients were enrolled and treated in an open-label, non-randomized, prospective IIT study in China in two different dose levels and with two different formulations. Patients were heavily pretreated, and all had previously received either autologous or donor derived CD19 or CD19/CD22 targeted CAR-T therapy. As of the January 28, 2022 data cutoff date, all four patients had received a single dose of GC502, including one patient at dose level 1 (DL1) 1.0x107 cells/kg and three patients at dose level 2 (DL2) 1.5x107 cells/kg. Patients received a Flu/Cy based lymphodepletion regimen prior to treatment with GC502. As highlighted in the AACR poster, three out of four patients achieved minimal residual disease negative complete response or complete response with incomplete count recovery (MRD- CR/CRi), and one patient achieved a partial response at month one and subsequently received allogeneic hematopoietic stem-cell transplantation (allo-HSCT) on day 39. Cytokine release syndrome (CRS) presented as Grade 2 and Grade 3 with no Grade 4 or 5 events. No immune effector cell-associated neurotoxicity syndrome (ICANS) or acute graft-versus-host disease (aGvHD) were observed.
Saturday, April 9, 2022
India's COVID-19 vaccine prices cut as booster program is extended
Serum Institute of India (SII) and Bharat Biotech have cut the prices of their COVID-19 vaccines as the country plans to offer booster doses to all adults from Sunday.
The cost of SII's Covishield will drop to 225 rupees ($2.96) a dose from 600 rupees for private hospitals, chief executive Adar Poonawalla said in a Tweet on Saturday.
"After discussion with the central government, SII has decided to revise the price of Covishield vaccine for private hospitals," he said.
Infections in India have fallen to their lowest in nearly two-years, with 1,150 new cases reported in the past 24 hours, with 83 deaths. The death toll in the country since the pandemic started is 521,656.
SII, the world's biggest vaccine maker, produces AstraZeneca's (AZN.L) COVID-19 vaccine under the brand name Covishield.
Of the 1.85 billion vaccine doses India has supplied to its population of 1.35 billion, 82% have been Covishield.
Bharat Biotech cut the price of its Covaxin vaccine to 225 rupees per dose from 1,200 rupees, the company's joint managing director Suchitra Ella said in a Tweet.
Those over 18 who received a second dose nine months ago will be eligible for the additional "precaution" dose, the health ministry said on Friday, using the government's term for boosters.
The booster programme, which started in January, is limited to frontline workers and the elderly and has so far administered 24 million doses.
When the programme is extended on Sunday, those outside the two priority categories will have to pay for the shots at privately run facilities, with no mixing and matching of vaccines allowed.
Arterys lands FDA go-ahead to expand its cardiac MRI-reading AI
Analyzing the results of an MRI scan can be a complex, time-consuming process for physicians. Outsourcing much of the work to artificial intelligence, however, can slash that time and effort by about a third, according to AI developer Arterys.
The San Francisco-based startup has built a handful of tools that use deep learning and other forms of AI to analyze a range of imaging data, including lung CT scans, chest X-rays and both brain and heart MRIs. The last of these is the subject of Arterys’ latest leap forward, which brought in a new FDA clearance—the company’s eighth to date—and added a handful of new features for the Cardio AI solution.
The cloud-based Cardio AI tool uses deep learning algorithms to rapidly take in and assess MRI scans of the heart, producing analyses Arterys says are as accurate as the segmentations performed manually by human experts—but in much less time.
The FDA green light was bestowed upon Arterys’ modules for T1 mapping and T2 quantification. The T1 mapping tool, which also calculates extracellular volume fraction (ECV), looks for variations in the heart muscle’s tissue. Those findings can then be used to diagnose conditions like myocardial inflammation, fibrosis and hypertrophy, while the ECV calculations measure the empty space in the tissue that may also play host to certain myocardial diseases.
T2 quantification, meanwhile, provides another characterization of the tissue of the heart muscle, helping physicians assess the severity of a case of myocardial infarction and detect swelling in patients with the condition.
In addition to the FDA’s signoff of those new features—which will allow them to be made commercially available in the U.S.—Arterys unveiled three other modules for the Cardio AI solution.
The first of these is a research-use-only tool that’s able to quantify ventricular dysfunction, adding overlays to the MRI that depict strain, strain rate and myocardial velocity. Another new addition assesses the volumes of each of the right and left atria, while the third automatically calculates the thickness of the heart’s walls.
Those and the T1 and T2 quantification tools join other features already embedded in the Cardio AI platform that offer 2D and 4D visualizations of the blood flow through the heart, semi-quantitative analyses of how well the muscle is functioning and more.
Johns Hopkins’ heart-scanning AI predicts cardiac arrests up to 10 years ahead
Researchers at Johns Hopkins University have developed an artificial intelligence approach they say can help predict if and when a person could die of cardiac arrest based on imaging scans of the heart.
By analyzing the patterns of scar tissue that can develop in the cardiac muscle over time due to heart disease, the researchers found that the AI algorithms could offer accurate predictions of a person’s risk up to 10 years ahead.
That scar tissue can affect how the heart’s timekeeping electrical pulses travel to the contracting ventricles, resulting in abnormal heart rhythms that can become dangerous if left untreated.
"Sudden cardiac death caused by arrhythmia accounts for as many as 20% of all deaths worldwide, and we know little about why it's happening or how to tell who's at risk," said Natalia Trayanova, a professor at Johns Hopkins and senior author of a paper published in Nature Cardiovascular Research.
The technology uses contrast-enhanced MRI scans of the heart combined with standard data points from the patient’s medical history that are typically used to generate cardiovascular risk factors such as age, weight, race and prescription drug use.
After gathering years of heart scans from hundreds of Johns Hopkins patients with cardiac scarring, the researchers said the AI was able to outperform physicians’ predictions that relied on simple visual estimates of scar features like their total volume and mass.
"The images carry critical information that doctors haven't been able to access," first author Dan Popescu, a former Johns Hopkins doctoral student, said in a statement. "This scarring can be distributed in different ways, and it says something about a patient's chance for survival. There is information hidden in it."
With predictions delivering about 74% accuracy when put up against an independent set of testing data gathered from 60 health centers across the U.S., the AI could help physicians personalize long-term treatments for heart disease.
“There are patients who may be at low risk of sudden cardiac death getting defibrillators that they might not need and then there are high-risk patients that aren't getting the treatment they need and could die in the prime of their life,” Trayanova said. “What our algorithm can do is determine who is at risk for cardiac death and when it will occur, allowing doctors to decide exactly what needs to be done.”
Other efforts to find helpful heart signals unviewable by the human eye have focused on spotting the signs of early heart disease in electrocardiogram data or ultrasound scans.
Researchers at the Mayo Clinic previously demonstrated that learning AI algorithms could be trained to find signs of low ejection fraction and poor heart performance based on a standard, 12-lead EKG reading—leading to 32% more diagnoses compared to standard diagnostic workups.
Meanwhile, a human-versus-AI study by the University of Oxford spinout Ultomics showed that the technology was more effective at predicting which COVID-19 patients would suffer severe heart complications, using data from ultrasound scans.
By viewing the contractions of the beating heart muscle and highlighting signs of damage caused by COVID-19, the AI could forecast potentially higher mortality rates both inside the hospital and in the months following treatment.
FDA ramps up cybersecurity efforts with stricter guidance for devicemakers
Important things come on a quadrennial basis: leap years, presidential elections, the Olympics and, apparently, edicts from the FDA about the need for heightened cybersecurity measures to protect connected medical devices.
The agency’s latest draft guidance (PDF) on the subject arrived this week, following previous releases in 2018 and 2014. The FDA noted that regular revisions and updates are especially necessary when it comes to the topic of cybersecurity because of “the rapidly evolving landscape and the increased understanding of the threats and their potential mitigations,” as well as an increasing number of hacks targeting devices and healthcare providers.
The guidance—which is accepting comments until early July, when the FDA will begin finalizing its recommendations—revolves around four core principles: the idea that cybersecurity is a key part of overall device safety, the need for security elements to be embedded throughout a device’s design, the importance of transparency in disclosing cybersecurity measures and vulnerabilities and a mandate that all potential vulnerabilities be explored in the device’s regulatory application.
Taken together, the FDA said, “These recommendations can facilitate an efficient premarket review process and help ensure that marketed medical devices are sufficiently resilient to cybersecurity threats.”
To ensure all four of those central principles are present in a device’s development and eventual FDA submissions, the agency recommends devicemakers create and adopt a Secure Product Development Framework, or SPDF, which it describes as “a set of processes that reduce the number and severity of vulnerabilities in products throughout the device lifecycle.”
An SPDF should comprise a devicemaker’s risk management efforts, the security architecture of each of its devices and details of its cybersecurity testing.
In the first category, the FDA offered up a handful of suggestions for risk management tactics that can then be described in a premarket submission. They include modeling all potential threats to a device and performing a thorough assessment of all bugs, defects and other anomalies in a device’s software before submitting it for approval. The FDA also asks developers to include all third-party components in their cybersecurity risk assessments, ideally compiling a “software bill of materials” that would list every single component of a device to make it easier to pinpoint the source of any future vulnerability.
A device’s security architecture, meanwhile, “defines the system and all end-to-end connections into and/or out of the system,” per the FDA. By submitting that information during the premarket review process, the agency will be better able to assess its safety and weigh any potential hacking risks.
Finally, alongside the typical tests of a device’s ability to address a designated health issue, the FDA is also asking devicemakers to put their products through the cybersecurity gauntlet—and submit those results in the same vein as clinical trial documentation, spanning security requirements, threat mitigation efforts and vulnerability and penetration testing.
Since finalizing its first cybersecurity guidance for medical devicemakers in 2014, the FDA has been steadily strengthening its efforts to ward off cyberattacks.
In early 2021, for example, the agency named its first-ever director of medical device cybersecurity within the Center for Devices and Radiological Health. It tapped Kevin Fu, Ph.D., an associate professor and director of the Security and Privacy Research Group at the University of Michigan, to fill the role in an acting capacity.
Maryland Gov. Hogan vetoes bill to expand abortion access
Maryland Gov. Larry Hogan vetoed a measure Friday that would expand access to abortion in the state by ending a restriction that only physicians can provide them and requiring most insurance plans to cover abortion care without cost.
The Republican governor, who isn’t ruling out a run for the White House in 2024 after his second term ends early next year, wrote that the bill “endangers the health and lives of women by allowing non-physicians to perform abortions.”
“The bill risks lowering the high standard of reproductive health care services received by women in Maryland,” wrote Hogan, who has previously said he personally opposes abortion though he considers it settled law in the state. “These procedures are complex and can, and often do, result in significant medical complications that require the attention of a licensed physician.”
Democrats, who control the General Assembly, passed the legislation with enough votes to override the veto before the scheduled adjournment of the legislative session Monday at midnight.