Clinical trial begins of Vaccitech lung cancer immunotherapeutic

 Cancer Research UK’s Centre for Drug Development, working with the Ludwig Institute for Cancer Research and Vaccitech, has begun a phase I/IIa clinical trial of a new lung cancer vaccine.

The novel immunotherapeutic, VTP-600, is not a preventative vaccine — it’s intended for patients who have recently been diagnosed with non-small cell lung cancer.

The initial trial will enrol 86 patients, across 10 specialist hospitals in the UK, testing for safety and efficacy in patients who are also receiving standard of care treatments.

Vaccitech and the Ludwig Institute are providing the drug while the Centre manages the trial and provides funding.

“We are excited to see that the first patient has been treated with the VTP-600 immunotherapeutic vaccine,” Dr. Nigel Blackburn, director of cancer research UK’s Centre for Drug Development, said in a statement. “NSCLC is the most common type of lung cancer but remains very hard to treat. If successful, this cutting-edge immunotherapy could provide an effective, much-needed new treatment to help more people survive their lung cancer.”

Like all immunotherapies, VTP-600 works by stimulating the body’s immune system to fight the cancer. The therapeutic delivers proteins which cause the immune system to produce T cells that will target certain antigens found on cancerous cells but not healthy cells. It’s delivered over a course of three shots, called a prime-boost approach.

“We’ve seen how our viral vector has transformed the world’s approach to sars-cov2 and has shown promising early results in chronic hepatitis B virus infection,” said Vaccitech CEO Bill Enright. “We see this partnership as another important validation of our prime boost platform’s utility in oncology as well as infectious disease.”

The trial is expected to last two to three years. If it goes well, the core technology could be adapted to breast, bowel, bladder and skin cancers, according to Cancer Research UK.

Vaccitech has an option to license the results of the trial but Cancer Research UK will have the right to move forward with future trials if the company chooses not to exercise the option.

https://pharmaphorum.com/news/clinical-trial-begins-of-lung-cancer-immunotherapeutic/

EQRx Sugemalimab plus chemo boosts lung cancer survival

 Lung cancer drug sugemalimab has delivered positive results following a phase 3 trial.

The GEMSTONE-302 study evaluated the efficacy and safety of the investigational anti-PD-L1 antibody, sugemalimab, in combination with chemotherapy as a first-line treatment for patients with stage four non-small cell lung cancer (NSCLC), versus using chemotherapy alone.

PD-1 inhibitors work against the protein, Programmed Death-Ligand 1 (PD-L1), which is found on the surface of many cells throughout the body. Some cancer cells contain large amounts of PD-L1, which helps them to evade the body’s immune system.

Dr Vince Miller, physician-in-chief at EQRx, said: “We are highly encouraged to see that sugemalimab in combination with chemotherapy demonstrates significant clinical benefit, including improvement in both progression-free survival (PFS) and overall survival (OS), when compared to placebo plus chemotherapy across a broad spectrum of patients with stage four non-small cell lung cancer in this phase 3 study.

“Price remains a barrier to accessing innovative therapies for many people with lung cancer around the world, despite the availability of multiple anti-PD-(L)1 therapies.”

EQRx’s ethos is to engage with global regulatory authorities to deliver a lower-cost treatment option to patients upon approval. Detailed results of the GEMSTONE-302 study will be presented at a future medical congress. 

The drive to tackle the disease is high, as every 15 seconds, an individual is diagnosed with lung cancer globally, and every 18 seconds, a person dies of the disease. It is the second most commonly diagnosed cancer and the leading cause of cancer deaths worldwide. In 2020, an estimated 2.2 million people were diagnosed with lung cancer.

NSCLC is the most common type of lung cancer, accounting for 84% of all lung cancer diagnoses. 

According to the British Lung Foundation, 85,000 people living in the UK have received a lung cancer diagnosis. This includes people living with the condition, those in remission and those who have been cured.

Lung cancer prevalence rates have risen by 23% since 2004, notes the BLF: “The earlier part of this trend may have been affected by changes in the way data were collated and incentivised. But prevalence still increased by 10% between 2008 and 2012. Stable incidence and rising prevalence point to improving lung cancer survival rates.”

https://pharmaphorum.com/news/sugemalimab-plus-chemo-boosts-lung-cancer-survival-trial-reveals/

New Mexico calls in National Guard to staff schools, child care centers

 New Mexico Gov. Michelle Lujan Grisham (D) on Wednesday announced a "Supporting Teachers and Families” initiative to encourage state workers and members of the National Guard to assist at schools struck by COVID-19 outbreaks. 

In a press release on Wednesday, the governor said that "extreme staffing shortages due to a surge in COVID-19 cases" prompted the initiative.

Specifically, the program encourages state workers and National Guard members to volunteer to get licensed as substitute pre-K-12 teachers or as child care workers so they can be available to help with in-person learning and child care.

“Our schools are a critical source of stability for our kids – we know they learn better in the classroom and thrive among their peers,” Lujan Grisham said in a statement.

“Our kids, our teachers and our parents deserve as much stability as we can provide during this time of uncertainty, and the state stands ready to help keep kids in the classroom, parents able to go to work and teachers able to fully focus on the critical work they do every single day in educating the next generation,” she added.

The governor's announcement noted that many schools in the state have been forced to move toward remote learning as staff members have either tested positive for the virus or been required to isolate due to exposure. 

COVID-19 cases in New Mexico have skyrocketed recently, with a 207 percent increase in cases in the past 14 days. As of Tuesday, the state reported a daily average of 5,557 cases, according to The New York Times. 

https://thehill.com/homenews/state-watch/590478-new-mexico-calls-in-national-guard-to-staff-schools-child-care-centers

Minn. AG sues COVID-19 testing lab over allegedly fraudulent results

 Minnesota's attorney general's office announced on Wednesday it was suing a national company that issues COVID-19 tests, citing concerns with fraudulent and deceptive practices.

The office filed the lawsuit in Hennepin County District Court against Illinois-based Center for COVID Control and its primary lab, Doctors Clinical Lab, accusing the company of having "failed to deliver test results, or delivered test results that were falsified or inaccurate," according to a Wednesday press release.

The lawsuit charges the company on four counts, including violating the Prevention of Consumer Fraud Act.

Attorney General Keith Ellison said in a statement he was going to hold the company accountable for "deceiving Minnesotans and undermining the public’s trust in testing."

“My job is to fight for Minnesotans’ security and help them live with dignity, safety, and respect," he said. "Making sure that Minnesotans have accurate tools to [keep] them safe from the COVID-19 pandemic is a key part of that job."

Other states have also received complaints about The Center for COVID Control, a business under investigation by the Centers for Medicare and Medicaid Services and the Oregon Department of Justice, USA Today reported.

The Center for COVID Control opened in 2020 and now has more than 300 testing sites with about 3,000 front line employees spread across the U.S., according to the company.

In Minnesota, pop-up testing locations failed to provide timely test results and sometimes never released results for patients at all, the attorney general's office said. Other people reported receiving test results without submitting a sample.

According to the attorney general's office, "former employees recounted finding samples in bags that were well over 48 hours old, being instructed by management to falsify dates of receipt, and being instructed to lie to consumers about their tests being inconclusive or negative when, in fact, the sample had not been tested."

In a Jan. 13 press release, The Center for COVID Control announced it was pausing testing operations until Jan. 22 to "ensure the highest customer service and diagnostic quality."

"Regrettably, due to our rapid growth and the unprecedented recent demand for testing, we haven't been able to meet all our commitments,” said CEO Aleya Siyaj in a statement. “We’ve made this difficult decision to temporarily pause all operations, until we are confident that all collection sites are meeting our high standards for quality."

https://thehill.com/regulation/healthcare/590501-minnesota-ag-sues-covid-testing-lab-over-allegedly-fraudulent-results

Myth vs. Fact: CMS Draft Decision on Alzheimer's Drugs

 With so much misinformation surrounding the draft National Coverage Determination (NCD) from the Centers for Medicare and Medicaid Services (CMS) not to cover the first class of Alzheimer's drugs, except in very limited circumstances, UsAgainstAlzheimer's is setting the record straight.

Myth: The draft determination applies only to a single drug: Aduhelm.

Fact: CMS leadership has repeatedly confirmed the draft NCD applies to the entire class of anti-amyloid monoclonal antibodies. It impacts promising drugs in late-stage development from Eisai Co., Eli Lilly & Co, Roche, and even Alzheimer's drugs not invented yet.

Myth: This is a normal exercise of CMS authority.

Fact: CMS has never refused to cover an on-label use of any FDA-approved therapeutic drug or decided in advance to deny coverage for an entire class of drugs. Prior use of Coverage with Evidence Development has been confined almost exclusively to medical devices.

Myth: The proposed decision protects the public.

Fact: Alzheimer's is a fatal disease, not occasional memory slips that are the normal part of aging. It is the 6th leading cause of death among Americans. No alternative treatments exist to slow progression of the disease. CMS, the nation's health insurance agency, is telling Alzheimer's patients it will effectively deny coverage for every drug in a class, regardless of the safety and efficacy those drugs show in FDA trials.

Myth: Patients will still have access; they just have to participate in clinical trials.

Fact: Scientists estimate approximately 1.2 million Americans might benefit from this class of drugs. Clinical trials typically enroll no more than 3,000 people, making these drugs unavailable for nearly every Medicare patient who might benefit.

Myth: This is only a short delay.

Fact: This draft decision is so unprecedented it is impossible to state definitively how long patients must wait. Some clinical trial experts estimate the NCD would delay patient access to these drugs until 2032 or later. Scientists agree these treatments are most effective in the early stages of the disease, so years of delay will mean it will be too late for hundreds of thousands of patients.

About UsAgainstAlzheimer's

UsAgainstAlzheimer's exists to conquer Alzheimer's disease. We take on the toughest problems; bring all of "Us" together to break down barriers; advocate for research that will speed treatments to market; and drive changes that matter most to people living with the disease. We will not rest until brain-span equals lifespan - for everyone.

 

 

 

 View original content to download multimedia:https://www.prnewswire.com/news-releases/myth-vs-fact-cms-draft-decision-on-alzheimers-drugs-301464216.html

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https://www.biospace.com/article/releases/myth-vs-fact-cms-draft-decision-on-alzheimer-s-drugs/

New tool for measuring pace of aging

 Researchers at Columbia University Mailman School of Public Health have developed a new blood test to measure the pace of biological aging. Based on an analysis of chemical tags on the DNA contained in white blood cells, called DNA methylation marks, the new test is named DunedinPACE, after the Dunedin Birth Cohort used to develop it. DunedinPACE (stands for Pace of Aging Computed from the Epigenome) is a new addition to a fast-growing list of DNA methylation tests designed to measure aging and contributes value-added over and above the current state of the art. The findings are published online in the journal e-Life.

"What makes DunedinPACE unique is that, whereas other tests aim to measure how old or young a person is, DunedinPACE measures whether you are aging quickly or slowly," said Daniel Belsky, PhD, assistant professor of epidemiology at Columbia Mailman School and a researcher at the Columbia Aging Center. This design could make DunedinPACE more a more sensitive tool to detect effects of interventions that aim to slow aging or of exposures that accelerate aging processes. "Whereas other measures of aging are designed to capture all aging-related change accumulated across the life course, our measure is focused on changes occurring over the recent past," explained Belsky. "What is striking is that, even with this more restricted focus, DunedinPACE is equally precise as the best of the currently available tests in predicting disease, disability, and mortality in the future, and it adds value to risk assessments over and above these measures."

Developed by Belsky and colleagues at Duke University and the University of Otago, DunedinPACE tracks changes in 19 biomarkers of organ-system integrity in the 1000-member Dunedin Study birth cohort, who were first enrolled in the study at birth in 1972-1973 and have been followed up ever since, most recently at the time of their 45th birthday. This study used data collected from the participants when they were all aged 26, 32, 38, and 45 years.

The use a single-year birth cohort to develop the measure ensures DunedinPACE is not contaminated by biases that may affect studies that compare older to younger people, including survival bias, historical differences in exposure. The analysis of changes that occurred within Study members' bodies as they aged over the 20-year follow-up also ensures that DunedinPACE measures aging-related changes occurring during adult life.

In addition to the Dunedin Study, the researchers also used data from the Understanding Society Study, the Normative Aging Study, the Framingham Heart Study, and the Environmental Risk (E- Risk) Longitudinal Twin Study.

In the current analysis, midlife and older adults with faster DunedinPACE were at increased risk for incident chronic disease, disability, and mortality; across the lifespan, DunedinPACE was correlated with measures of biological age derived from blood chemistry and DNA methylation data, and with research participants' subjective perceptions of their own health. It also indicated faster Pace of Aging in young adults with histories of exposure to poverty and victimization.

"In sum, DunedinPACE represents a novel measure of aging that can complement existing DNA methylation measures of aging to help advance the frontiers of geroscience," noted Belsky, who is also with the Robert N. Butler Columbia Aging Center, Columbia Mailman School.

The current analysis establishes DunedinPACE as a novel single-time-point measure that quantifies Pace of Aging with whole blood samples, that can be readily implemented in most DNA methylation datasets, making it immediately available for testing in a wide range of existing datasets as a complement to existing methylation measures of aging.

"There is growing interest in technologies to measure a biological age, defined as how much older or younger a person is biologically than their birthdate would predict. Our study reveals that it is also possible to measure Pace of Aging, or how fast a person's body is declining. Together, these measurements can help us understand the factors that drive accelerated aging in at-risk populations and identify interventions that can slow aging to build aging health equity."

Co-authors are A Caspi, TE Moffitt, King's College, UK and Duke University; K Sugden, K Chamarti, HL Harrington, R Houts, B Williams, Duke University; R Poulton, University of Otago, NZ; L Arseneault, King's College, UK; A. Baccarelli, Columbia University Mailman School of Public Health; X Gao, Peking University; E Hannon, J Mill, University of Exeter, UK; M Kothari, D Kwon, Robert N. Butler Columbia Aging Center, Columbia Mailman School of Public Health; J Schwartz, C Wang, Harvard TH Chan School of Public Health; and P Vokonas, Veterans Affairs Boston Healthcare System, Boston University School of Medicine

The research was supported by National Institute on Aging (grants AG032282,AG061378,AG066887); Medical Research Council (grant P005918).

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Story Source:

Materials provided by Columbia University's Mailman School of Public Health. Note: Content may be edited for style and length.

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Journal Reference:

1. Daniel W Belsky, Avshalom Caspi, David L Corcoran, Karen Sugden, Richie Poulton, Louise Arseneault, Andrea Baccarelli, Kartik Chamarti, Xu Gao, Eilis Hannon, Hona Lee Harrington, Renate Houts, Meeraj Kothari, Dayoon Kwon, Jonathan Mill, Joel Schwartz, Pantel Vokonas, Cuicui Wang, Benjamin S Williams, Terrie E Moffitt. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife, 2022; 11 DOI: 10.7554/eLife.73420

https://www.sciencedaily.com/releases/2022/01/220118103713.htm

Arthritis-related gene also regenerates cartilage in joints and growth plates

 The IL-6 family of proteins has a bad reputation: it can promote inflammation, arthritis, autoimmune disease and even cancer. However, a new USC-led study published in Communications Biology reveals the importance of IL-6 and associated genes for maintaining and regenerating cartilage in both the joints and in the growth plates that enable skeletal growth in children.

"We show, for the first time, that the IL-6 family, previously almost exclusively associated in the musculoskeletal field with arthritis, bone and muscle loss, and other chronic inflammatory diseases, is required for the maintenance of skeletal stem and progenitor cells, and for the healthy growth and function of the joints and spine," said the study's corresponding author Denis Evseenko, who is the J. Harold and Edna LaBriola Chair in Genetic Orthopedic Research, and an associate professor of orthopaedic surgery, and stem cell biology and regenerative medicine at the Keck School of Medicine of USC. "Our study establishes a link between inflammation and regeneration, and may explain why stem and progenitors are exhausted in chronic inflammation."

In the study, first author Nancy Q. Liu from USC and her colleagues took a close look at a key gene activated by IL-6: STAT3. In both lab-grown human cells and in mice, the scientists demonstrated that STAT3 is critical for the proliferation, survival, maturation and regeneration of cartilage-forming cells in the joints and growth plates. When the gene ceased to function, cartilage-forming cells became increasingly dysfunctional over time, resulting in smaller body size, prematurely fused growth plates, underdeveloped skeletons and mildly degenerated joint cartilage.

Mice experienced the same issues when they lacked a protein called glycoprotein 130 (gp130), which all IL-6 proteinsuse to activate Stat3. Deactivating another gene Lifr, which encodes a protein that works with gp130 to recognize one of the IL-6 proteins called Lif, produced similar but milder skeletal and cartilage changes.

In mice lacking gp130, the scientists could restore normal growth plates by over-activating Stat3 -- although this also caused an overgrowth of cartilage that led to other skeletal abnormalities.

Interestingly, the researchers noted significant sex-related differences: when Stat3 ceased to function, females experienced more severe cartilage and skeletal changes than males. To understand why, the researchers altered estrogen levels in mice, as well as in lab-grown pig cartilage cells. In both cases, estrogen increased the amount and activity of Stat3, suggesting that females might rely more heavily on this gene.

The study has clinical implications for the use of existing drugs that inhibit STAT3 to curb inflammation in autoimmune diseases: these drugs may also interfere with growth and regeneration.

Conversely, the Evseenko Lab has leveraged their understanding of the nuances of STAT3 and associated genes and proteins to develop a highly targeted drug with the potential to regenerate joint cartilage without triggering inflammation. This drug will soon be tested in human clinical trials.

"Our findings really shift the paradigm and challenge the existing dogmas in the field about how IL-6, STAT3, and associated genes and proteins influence not only inflammation, but also regeneration," said Evseenko.

About the study

Additional co-authors of the study include: Yucheng Lin from USC, Nanjing Medical University, and Southeast University in Nanjing; Liangliang Li and Dawei Geng from USC and Nanjing Medical University; Jinxiu Lu, Zorica Buser, Jenny Magallanes, Jade Tassey, Ruzanna Shkhyan, Arijita Sarkar, Siyoung Lee, Youngjoo Lee, Frank A. Petrigliano, Ben Van Handel, and Tea Jashashvili from USC; Jiankang Zhang from USC and Sichuan University; Noah Lopez and Karen Lyons from UCLA; and Liming Wang from Nanjing Medical University and Sichuan University.

The work was supported by federal funding from the National Institutes of Health (grants R01AR071734 and R01AG058624) and the Department of Defense (grant W81XWH-13-1-0465), and the California Institute for Regenerative Medicine (grant TRAN1-09288).

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Story Source:

Materials provided by Keck School of Medicine of USC. Original written by Cristy Lytal. Note: Content may be edited for style and length.

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Journal Reference:

1. Nancy Q. Liu, Yucheng Lin, Liangliang Li, Jinxiu Lu, Dawei Geng, Jiankang Zhang, Tea Jashashvili, Zorica Buser, Jenny Magallanes, Jade Tassey, Ruzanna Shkhyan, Arijita Sarkar, Noah Lopez, Siyoung Lee, Youngjoo Lee, Liming Wang, Frank A. Petrigliano, Ben Van Handel, Karen Lyons, Denis Evseenko. gp130/STAT3 signaling is required for homeostatic proliferation and anabolism in postnatal growth plate and articular chondrocytes. Communications Biology, 2022; 5 (1) DOI: 10.1038/s42003-021-02944-y

https://www.sciencedaily.com/releases/2022/01/220118145941.htm