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UK says it won’t purchase AstraZeneca’s Covid treatment due to ‘insufficient’ Omicron data — reports

Weeks after evidence suggested current Omicron subvariants may be less susceptible to AstraZeneca’s prophylactic Covid-19 treatment Evusheld, the UK…

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Weeks after evidence suggested current Omicron subvariants may be less susceptible to AstraZeneca’s prophylactic Covid-19 treatment Evusheld, the UK has reportedly decided against buying doses for now.

The UK’s Department of Health said it won’t procure Evusheld doses due to “insufficient data on the duration of protection offered by Evusheld in relation to the omicron variant,” according to the BMJ, a peer-reviewed trade journal published by the British Medical Association.

Evusheld, which is a combination of tixagevimab and cilgavimab, will now be evaluated by the National Institute for Health and Care Excellence (NICE). However, that report isn’t expected until next April, according to the BBC, which was among the first to report the news.

The drug was authorized in the US back in December, based on data that suggested recipients saw protection through six months. In a primary analysis, recipients saw a 77% reduced risk of Covid infection compared to placebo, according to the FDA.

In June, feeling pressure from Omicron subvariants, the FDA updated the Evusheld fact sheet to recommend repeat dosing every six months with 300 mg.

“Nonclinical data and pharmacokinetic modeling suggest that activity against these subvariants [BA.2, BA.2.12.1, BA.4, and BA.5] may be retained for six months at drug concentrations achieved following an Evusheld dose of 300 mg of tixagevimab and 300 mg cilgavimab,” regulators noted at the time.

However, July correspondence in the New England Journal of Medicine suggested that current Omicron subvariants may be less susceptible to AstraZeneca’s blockbuster drug. The researchers from Japan, the University of Wisconsin, Johns Hopkins and Icahn School of Medicine at Mount Sinai wrote that Eli Lilly’s bebtelovimab appeared to be effective across three different Omicron sublineages – BA.2.12.1, BA.4, and BA.5.

“However, in clinical use, these variants may be less susceptible to combination therapy with casirivimab and imdevimab and with tixagevimab and cilgavimab,” the researchers wrote.

AstraZeneca countered back in July that “studies have shown that Evusheld neutralizes all known variants of concern, including BA.4/5.” And on the company’s Q2 call, execs maintained that “efficacy is remaining very robust.”

A company spokesperson declined to comment on Monday.

Iskra Reic

“The main limitation of our study is the lack of clinical data on the efficacy of these monoclonal antibodies and antiviral drugs for the treatment of patients infected with BA.2.12.1, BA.4, or BA.5 subvariants,” researchers noted in the NEJM piece.

Sales for Evusheld and the company’s Covid-19 vaccine Vaxzevria were down last quarter compared to Q1 2022, coming in at $445 million and $451 million, respectively. While CEO Pascal Soriot expects Vaxzevria sales will continue to fall this year, he thinks Evusheld will grow.

“We are pleased to see strong demand, increased demand for Evusheld, because it is clear that it’s really important to protect the immunocompromised patients … due to the fact that they are not able to develop the immune response after vaccination,” Iskra Reic, executive VP of vaccines and immune therapies, said on the Q2 call. “We do believe that demand will continue.”

The UK’s Department of Health and Social Care has not responded to a request for comment as of press time.

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Spread & Containment

Zika Vaccine Targeting Nonstructural Viral Proteins Found Effective in Mice

UCLA scientists report positive preclinical results on the safety and efficacy of an RNA vaccine (ZVAX) against the mosquito borne Zika virus that severely…

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Positive preclinical results on the safety and efficacy of an RNA vaccine (ZVAX) against the mosquito-borne Zika virus that severely compromises brain development in children of infected mothers, were published in the journal Microbiology Spectrum on September 28, 2022 “Replication-Deficient Zika Vector-Based Vaccine Provides Maternal and Fetal Protection in Mouse Model.” The investigators tested the vaccine in pregnant mice and report the vaccine prevents systemic Zika infection in both mothers and developing fetuses.

“The ongoing COVID-19 pandemic has shown us the power of a strong pandemic preparedness plan and clear communication about prevention methods—all culminating in the rapid rollout of safe and reliable vaccines,” said senior author of the study, Vaithilingaraja Arumugaswami, DVM, PhD, an associate professor of molecular and medical pharmacology at the University of California, Los Angeles (UCLA). “Our research is a crucial first step in developing an effective vaccination program that could curb the spread of Zika virus and prevent large-scale spread from occurring.”

Vaithilingaraja Arumugaswami, DVM, PhD, an associate professor of molecular and medical pharmacology at the University of California, Los Angeles (UCLA) is a co-senior author of the study.

Engineering the vaccine

The experimental vaccine is composed of RNA that encodes nonstructural proteins found within the pathogen that trigger an immune response against the virus.

Arumugaswami said, “Engineering the vaccine involved deleting the part of the Zika genome that codes for the viral shell. This modification both stimulates an immunogenic reaction and prevents the virus from replicating and spreading from cell to cell.”

Eliminating structural proteins that mutate rapidly to escape the immune system also ensures that the vaccine trains the recipient’s immune system to recognize viral elements that are less likely to alter. The researchers packaged the replication deficient Zika vaccine particles in human producer cells and verified antigen expression in vitro.

Nikhil Chakravarty, a co-author of the study and student at the UCLA Fielding School of Public Health
oversaw data analysis and writing of the manuscript.

“We deleted not just the gene responsible for encoding the capsid, but also those encoding the viral envelope and membrane. This vaccine is replication-deficient—it cannot spread among cells,” said co-author of the study, Nikhil Chakravarty, a master’s student at the UCLA Fielding School of Public Health.

Chakravarty clarified, “The deletion itself does not lead to stimulation of immune response but it makes this vaccine safer by rendering it replication deficient. The nonstructural proteins encoded by the RNA packaged in the vaccine stimulate more of a T-cell immune response that can specifically recognize Zika-infected cells and prevent viral replication and the spread of infection.”

The team showed increased effector T cell numbers in vaccinated versus unvaccinated mouse models. Using mass cytometry, the researchers showed high levels of splenic CD81 positive T cells and effector memory T cell responses and low levels of proinflammatory cell responses in vaccinated animals, suggesting that endogenous expression of the nonstructural viral proteins by the vaccine induced cellular immunity. There were no changes in antibody mediated humoral immunity in the vaccinated mice.

Co-author Gustavo Garcia, Jr., oversaw and conducted much of the experimentation reported in the study.

“We saw complete protective immunity against Zika virus in both pregnant and nonpregnant animals, speaking to the strength and utility of our vaccine candidate,” said Chakravarty. “This supports the deployment of this vaccine in pregnant mothers—the population, perhaps, most at need—upon further clinical evaluation. This would help mitigate some of the socioeconomic fallout from a potential Zika outbreak, as well as prevent neurological and developmental deficits in Zika-exposed children.”

The investigators administered the RNA vaccine using a prime-boost regimen where an initial dose was followed up by a booster dose. To estimate the durability of the vaccine, the researchers monitored the mice for a month-and-a-half, which is equivalent to approximately seven years in humans.

Chakravarty said, “Since the vaccine is geared toward stimulating T-cell response, we anticipate it will induce longer-lasting immunity than if it were just stimulating antibody immune response.”

Pandemic preparedness

The global Zika outbreak in 2016, led to efforts in developing effective therapies and vaccines against the virus. However, no vaccines or treatments have been approved for Zika virus yet.

“Other Zika vaccine candidates mainly focused on using structural proteins as immunogens, which preferably stimulates antibody response. Our candidate is unique in that it targets nonstructural proteins, which are more conserved across viral variants, and stimulate T-cell-mediated immunity,” said Chakravarty.

Epidemiological studies have shown that the Zika virus spreads approximately every seven years. Moreover, the habitats of Zika-spreading mosquitoes are increasing due to climate change, increasing the likelihood of human exposure to the virus.

“Given that RNA viruses—the category to which both Zika and the SARS family of viruses belong—are highly prone to evolving and mutating rapidly, there will likely be more outbreaks in the near future,” said Arumugaswami.

Kouki Morizono, MD, PhD, an associate professor of medicine at UCLA is a co-senior author of this study.

“It’s only a matter of time before we start seeing the virus spread again,” said Kouki Morizono, MD, PhD, an associate professor of medicine at UCLA and co-senior author of this study.

Before the vaccine candidate can be tested in humans, the researchers will be test it non-human primate models.

The post Zika Vaccine Targeting Nonstructural Viral Proteins Found Effective in Mice appeared first on GEN - Genetic Engineering and Biotechnology News.

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Carl H. June is recipient of inaugural Maria I. New International Prize for Biomedical Research

New York, NY (September 29, 2022) – The Icahn School of Medicine at Mount Sinai will award its inaugural 2022 Maria I. New International Prize for Biomedical…

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New York, NY (September 29, 2022) – The Icahn School of Medicine at Mount Sinai will award its inaugural 2022 Maria I. New International Prize for Biomedical Research to cancer and HIV cellular therapy pioneer Carl H. June, MD, for his groundbreaking work in immunotherapy. Dr. June is most widely known as one of the inventors of CAR T cell therapy for cancer, which has already led to FDA-approved treatments for lymphoma, leukemia, and multiple myeloma.

Credit: Carl June, MD

New York, NY (September 29, 2022) – The Icahn School of Medicine at Mount Sinai will award its inaugural 2022 Maria I. New International Prize for Biomedical Research to cancer and HIV cellular therapy pioneer Carl H. June, MD, for his groundbreaking work in immunotherapy. Dr. June is most widely known as one of the inventors of CAR T cell therapy for cancer, which has already led to FDA-approved treatments for lymphoma, leukemia, and multiple myeloma.

Dr. June will receive a prize of $20,000 and will present the Maria I. New Distinguished Lecture during a ceremony to be held in New York City in November.

Dr. June is the Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine, Director of the Center for Cellular Immunotherapies, and Director of the Parker Institute for Cancer Immunotherapy, all at the Perelman School of Medicine at the University of Pennsylvania. The prize is meant to honor medical pioneers in the tradition of Dr. Maria I. New, whose achievements demonstrated over six decades of outstanding commitment to breakthrough research.

“Carl June’s discoveries helped usher a new era in cancer treatment options,” says Mone Zaidi, MD, PhD, MACP, Director of Mount Sinai’s Center for Translational Medicine and Pharmacology, and Mount Sinai Professor of Clinical Medicine at the Icahn School of Medicine at Mount Sinai, who chaired the international jury that awarded the Maria I. New International Prize for Biomedical Research. “As its inaugural recipient, Carl exemplifies a distinguished scientist whose achievements have led to a transformative treatment paradigm for otherwise debilitating cancers, and by doing so, has upheld the legacy of Dr. Maria New and her lifetime contributions.”

Chimeric antigen receptor T cell immunotherapy (CAR T), which Dr. June helped create, is a type of cancer therapy that harnesses the body’s own immune system to fight cancer. T cells, a type of white blood cell, are removed from the patient and reprogrammed to recognize and attack cancer cells when returned to the body. Today, six CAR T cell therapies have been approved by the U.S. Food and Drug Administration, and clinical trials targeting many additional cancers are underway worldwide.

In the early 1990s, Dr. June began studying T cells in HIV-positive patients and patients with AIDS. He discovered that he could take T cells from a patient with AIDS, grow them in the lab, give them back to the patient, and their T cell counts would improve. His “eureka” moment came when he realized these CAR T cells could survive in patients and multiply without spreading HIV.

“The pandemic has emphasized the importance of biomedical research. One critical way to accelerate medical innovation is to ensure that we’re recognizing leading biomedical researchers: they are at the forefront of advancements in medicine, seeking answers to the most pressing needs in human health and helping millions of people live longer, healthier lives,” says Pulitzer Prize-winning author and economic historian Dr. Daniel Yergin, who, along with his wife, foreign policy expert Dr. Angela Stent, generously supported the prize.

“We couldn’t be prouder of the prize, developed in honor of the revered Dr. New, a giant in pediatric endocrinology and a global role model in combining breakthrough research with clinical impact. And the extraordinarily impactful work of Carl June epitomizes the value of Maria New’s life work and the outstanding contributions to medicine that this award will recognize.”

Eric J. Nestler, MD, PhD, Nash Family Professor of Neuroscience, Director of The Friedman Brain Institute, Dean for Academic Affairs at Icahn Mount Sinai, and Chief Scientific Officer of the Mount Sinai Health System, says, “It is an honor for the Icahn School of Medicine to host this new biomedical research award in recognition of one of our long-time star faculty members.”

“Through this annual prize, we celebrate the values exemplified by Dr. New and her transformative research at both the bench and bedside for over 60 years while also recognizing the work of exceptional physician-scientists who have made or are likely to make seminal contributions to patient care,” Dr. Nestler says. “We are delighted to contribute to biomedical research with this award, which is open to applicants from around the world. And we are profoundly grateful to Dan Yergin and Angela Stent for making it possible.”

The prize winners are selected by an international jury of prominent science community members. It is administered by Mount Sinai’s Center for Translational Medicine and Pharmacology, in conjunction with the Departments of Pediatrics, Medicine, and Pharmacological Sciences, under the dedicated leadership of Dr. Zaidi.

The jury members are Nobel laureate Aaron Ciechanover, MD, DSc, Distinguished University Professor at The Rappaport Family Technion Integrated Cancer Center in Haifa, Israel; Nancy Andrews, MD, Executive Vice President, and Chief Scientific Officer at Boston Children’s Hospital; Nancy Brown, MD, Jean and David W. Wallace Dean, Yale School of Medicine in New Haven, Connecticut; Bert W. O’Malley, MD, Tom Thompson Distinguished Service Professor of Molecular and Cellular Biology and Chancellor at Baylor College of Medicine in Houston, Texas; and Anna Wedell, MD, PhD, Professor of Medical Genetics in the Department of Molecular Medicine and Surgery at the Karolinska Institutet in Stockholm, Sweden.

“We extend our sincere gratitude to the distinguished members of the international jury for their precious time and effort in selecting a winner from a wide pool of outstanding nominees,” Dr. Zaidi says.

The Maria I. New International Prize for Biomedical Research

The Maria I. New International Prize for Biomedical Research was created in honor of the esteemed career of Maria I. New, MD, one of the world’s foremost pediatricians and a devoted member of the Mount Sinai community. It will be awarded annually to distinguished biomedical researchers for lifetime scientific achievements that have led, or may lead to, new ways to prevent and treat human disease. The award is generously supported by the Pulitzer Prize-winning author and economic historian Dr. Daniel Yergin and his wife, foreign policy expert Dr. Angela Stent.

The nomination cycle for the 2023 Prize begins on February 1, 2023, and closes on May 31, 2023. To learn more about the nomination process, contact Susan Babunovic at susan.babunovic@mssm.edu. 

Maria I. New, MD, Biography

Over the past half-century, Maria I. New, MD, has earned a reputation as one of the nation’s leading pediatric endocrinologists. Her studies of congenital adrenal hyperplasia (CAH)—a deficiency in the adrenal system that causes gender ambiguity in females and precocious sexual development in males—have led to treatments to correct the disorder before the baby is born. Her groundbreaking identification of a new form of hypertension, “apparent mineralcorticoid excess,” has resulted in a new area of receptor biology.

Since joining the Icahn School of Medicine at Mount Sinai in New York City in 2004, Dr. New has continued her work as a Professor of Pediatrics and of Genetics and Genomic Sciences. She is also the Founding Director of Mount Sinai’s Adrenal Steroid Disorders Program.

A member of the National Academy of Sciences, among several other prestigious academies, Dr. New has demonstrated a lifetime dedication to biomedical research and clinical care, and her training of a generation of pediatricians and endocrinologists continues to have a far-reaching impact on the lives of patients and the medical community at large.

About the Icahn School of Medicine at Mount Sinai

The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the eight- member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to a large and diverse patient population. 

Ranked 14th nationwide in National Institutes of Health (NIH) funding and among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges, Icahn Mount Sinai has a talented, productive, and successful faculty. More than 3,000 full-time scientists, educators, and clinicians work within and across 34 academic departments and 35 multidisciplinary institutes, a structure that facilitates tremendous collaboration and synergy. Our emphasis on translational research and therapeutics is evident in such diverse areas as genomics/big data, virology, neuroscience, cardiology, geriatrics, as well as gastrointestinal and liver diseases.

Icahn Mount Sinai offers highly competitive MD, PhD, and master’s degree programs, with current enrollment of approximately 1,300 students. It has the largest graduate medical education program in the country, with more than 2,000 clinical residents and fellows training throughout the Health System. In addition, more than 550 postdoctoral research fellows are in training within the Health System.

A culture of innovation and discovery permeates every Icahn Mount Sinai program. Mount Sinai’s technology transfer office, one of the largest in the country, partners with faculty and trainees to pursue optimal commercialization of intellectual property to ensure that Mount Sinai discoveries and innovations translate into healthcare products and services that benefit the public.

Icahn Mount Sinai’s commitment to breakthrough science and clinical care is enhanced by academic affiliations that supplement and complement the School’s programs.

Through the Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai. Additionally, MSIP develops research partnerships with industry leaders such as Merck & Company, AstraZeneca, Novo Nordisk, and others.

The Icahn School of Medicine at Mount Sinai is located in New York City on the border between the Upper East Side and East Harlem, and classroom teaching takes place on a campus facing Central Park. Icahn Mount Sinai’s location offers many opportunities to interact with and care for diverse communities. Learning extends well beyond the borders of our physical campus, to the eight hospitals of the Mount Sinai Health System, our academic affiliates, and globally.

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*  Mount Sinai Health System Member Hospitals: The Mount Sinai Hospital; Mount Sinai Queens; Mount Sinai Beth Israel; Mount Sinai West (previously known as Mount Sinai Roosevelt); Mount Sinai Morningside (previously known as Mount Sinai St. Luke’s); Mount Sinai Brooklyn; New York Eye and Ear Infirmary of Mount Sinai; and Mount Sinai South Nassau (previously known as South Nassau Communities Hospital).

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FDA clears Dupixent as first drug for rare skin disorder

Sanofi and Regeneron have claimed the first approval in the US for a drug for prurigo nodularis, after
The post FDA clears Dupixent as first drug for rare…

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Sanofi and Regeneron have claimed the first approval in the US for a drug for prurigo nodularis, after the FDA gave a green light to Dupixent as a treatment for adults with the rare skin disease following a priority review.

There are about 75,000 adults in the US living with prurigo nodularis who are in desperate need of new treatment options, according to the two drugmakers.

The disorder – driven by type 2 inflammation characterised by an antibody-based immune response – causes hard lumps or nodules to form on the skin that are so itchy they can lead patients to scratch themselves to the point of bleeding or pain.

At the moment, treatment typically involves oral or topical corticosteroids, antihistamines, and some antidepressant drugs, but responses are often inadequate, vary widely between patients, and come with the burden of safety risks if used long-term.

Dupixent (dupilumab) has been approved on the back of two phase 3 trials in patients with prurigo nodularis whose symptoms were inadequately controlled with current drugs.

The PRIME and PRIME2 studies both showed that the IL-4 and IL-13 inhibitor significantly improved disease signs and symptoms compared to placebo, including reduction in itch and skin lesions.

In almost half (45%) of patients, Dupixent treatment resulted in clear or almost clear skin after 24 weeks’ treatment, compared to 16% of controls, and patients also report significantly greater improvements in measures of health-related quality of life, skin pain, and symptoms of anxiety and depression.

Dupixent is already approved to treat atopic dermatitis, as well as other indications involving type 2 inflammation, including severe asthma, chronic rhinosinusitis with nasal polyposis, and eosinophilic oesophagitis.

“Dupixent has already transformed the treatment landscape of several diseases driven by type 2 inflammation […] and been prescribed to more than half a million patients around the world for its approved indications,” said Regeneron’s chief scientific officer George Yancopoulos in a statement.

“With this approval, those suffering with prurigo nodularis finally have a medicine to address the debilitating signs and symptoms of the disease,” he added.

Sales of Dupixent rocketed 43% to around $2 billion in the second quarter, driven by demand in its main atopic dermatitis and severe asthma indications – fuelled by approvals in earlier age groups – as well as smaller add-on indications, such as oesophagitis.

Sanofi and Regeneron have predicted that Dupixent could make around $13 billion a year at peak, which would propel the drug into the top five biggest pharmaceutical sellers behind brands like AbbVie’s immunology blockbuster Humira (adalimumab), Merck & Co’s cancer immunotherapy Keytruda (pembrolizumab), and COVID-19 vaccines.

The drug is also being tested in some forms of chronic obstructive pulmonary disease (COPD) and various conditions leading to urticaria (hives), although it fell short in a phase 3 trial in chronic spontaneous urticaria (CSU) earlier this year.

Development in peanut allergy has also been discontinued, said Sanofi in its second-quarter update.

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