Shionogi's COVID-19 vaccine matches Pfizer's Comirnaty in booster trial

 Shionogi’s COVID-19 vaccine candidate has held its own against Pfizer’s Comirnaty in a study of the effect of booster shots on antibody levels, offering the company encouragement as it barrels toward a filing for approval of S-268019 in Japan.

The clinical trial randomized 206 adults to receive a shot of S-268019 or Comirnaty six months or more after they completed a primary two-dose series with the Pfizer-BioNTech vaccine. Shionogi designed the clinical trial to compare the immunogenicity of its recombinant protein-based vaccine to that of Pfizer’s market-leading mRNA shot.

S-268019 passed the test. Shionogi found its vaccine was noninferior to Comirnaty against the primary endpoint, which looked at neutralizing antibody titers 29 days after the administration of the booster shot. 

The safety and tolerability data presented by Shionogi are free from red flags. Fever, headache, fatigue, muscle aches and injection site pain were the most frequent treatment-related adverse events, as they have been in studies of other COVID-19 vaccines. Most solicited local and systemic events were mild, and the incidence of solicited events was lower in the S-268019 cohort.

The data drop is a small step on the path to pivotal readouts. Shionogi is running four other phase 2/3 or phase 3 clinical trials, including a study that is aiming to enroll 50,000 subjects to assess whether giving S-268019 to unvaccinated people protects them from symptomatic COVID-19. The other, smaller trials are comparing S-268019 to AstraZeneca’s Vaxzevria and as a booster to Moderna’s Spikevax.

Shionogi only started the 50,000-subject phase 3 late last year but it is already gearing up for approval, opening talks with Japan’s Pharmaceuticals and Medical Devices Agency about a filing last month.

https://www.fiercebiotech.com/biotech/shionogis-covid-19-vaccine-matches-pfizers-comirnaty-booster-trial

Editas shares boosted as patent office rules for Broad's CRISPR patents, but fight will continue

 The U.S. Patent and Trademark Office has ruled in favor of the Broad Institute of MIT and Harvard in a dispute over the patents around CRISPR gene editing technology.

The decision is part of a long-running legal battle brought by two universities and one of the founders of the gene editing technique, Nobel Prize winner Emmanuelle Charpentier, Ph.D. 

Charpentier and fellow Nobel Prize laureate Jennifer Doudna, Ph.D., created a type of genetic scissors that can be used to cut any DNA molecule. This was dubbed CRISPR/Cas9, and it has been used by dozens of biotechs to create gene editing therapies that could someday provide one-time cures for diseases. Editas Medicines is among the companies doing just that using technology licensed from Broad. 

The patent office has determined Broad was the first group to invent CRISPR/Cas9 for editing a certain type of human cell that can be used to make medicines—not Charpentier, the University of California (UC) and the University of Vienna. The group is collectively referred to as CVC. 

Editas CEO James Mullen said both groups made important contributions to the science that ultimately led to gene editing in medicine, but the decision “reaffirms the strength of our foundational intellectual property,” according to an after-market release Monday. The Editas license covers patents for CRISPR/Cas9 and CRISPR/Cas12a gene editing in all human cells, the company said. 

Editas' shares climbed over 10% in after-market trading Monday to $18.90 apiece. The bump helped bring the company closer to the $19 range it was sitting at in February before Chief Medical Officer Lisa Michaels, M.D., was relieved of her duties without explanation. 

The decision has had the opposite impact on other gene editing companies. Intellia shares dropped almost 17% on Tuesday morning to $81.92, even though the company dropped some much anticipated data at market close on Monday. CRISPR Therapeutics was down just over 6% to $57.51 as of 11:34 a.m. ET on Tuesday. 

Intellia's patents are with UC and cross licensed from CRISPR Tx, ERS Genomics and Caribou Biosciences. 

Back in 2018, a federal appeals court found “no interference-in-fact" between CRISPR patents held by the Broad and patents sought by UC. Chardan Research noted that this earlier decision was a risk because it could block IP from companies that hold licenses with the UC group, which would apply to "many if not all of Intellia's programs."

The latest news is not the end of the dispute. The decision could be appealed to the federal circuit court, but for now it ends the “patent interference” in the U.S. by the challengers, according to Editas. 

In a statement, UC-Berkeley said the institution holds 40 other patents that were not subject to the ruling that cover various components of CRISPR-Cas9 genome editing systems. At issue in this matter were 13 patents, which UC said "remain under challenge." 

"UC is disappointed by the PTAB’s decision and believes the PTAB made a number of errors," the statement said. The group is considering "various options to challenge this decision."

Intellia supports the continued challenge, and said in the meantime, the biotech will focus on continuing to develop CRISPR/Cas9 therapeutics and generating its own IP. 

"We are carefully reviewing the decision and are confident CVC will find a path forward to affirm their IP rights, including the possibility of an appeal to the federal circuit," the company said. "CVC remains in a strong IP position in the U.S. and worldwide, and this decision does not impact any of our ongoing research and development plans."

Cambridge, Massachusetts-based Editas presented initial data on its first human clinical trials last year, which were conducted for the vision loss therapy EDIT-101. 

The Broad Institute is a genomic research institute that brings together researchers from MIT and Harvard. 

https://www.fiercebiotech.com/biotech/editas-shares-boosted-patent-office-rules-favor-broads-crispr-patents

3 in 4 infusion pumps vulnerable to cyberattacks: study

 As many as 75% of infusion pumps connected to hospital networks may be vulnerable to digital attacks, potentially putting patients at risk or exposing private data, according to a report from a group of cybersecurity researchers.

Palo Alto Networks and its Unit 42 Threat Intelligence team used crowdsourced data from scans of more than 200,000 smart infusion pumps and discovered 3 in 4 had known security gaps. 

Some of these vulnerabilities could allow an attacker to remotely intercept unencrypted communications from the device or permit an unauthorized person to change how the pump delivers intravenous medications. Other attempts may be less likely and would only be exploited by someone with physical access to the machine.

Altogether, the company’s report identified more than 40 direct cybersecurity flaws. It listed some of the most common issues—with each traced back to more than half of the vulnerable pumps analyzed—as having been publicly documented since 2016 or 2019.At the same time, many devices had one or more of about 70 types of known security shortcomings associated with Internet of Things hardware.

Some of the most commonly observed weaknesses related to leaving usernames and passwords unchanged from the device’s default factory settings—what Palo Alto Networks charitably described as a “security no-no.” These login credentials can be easily found in product manuals available online.

And while the FDA and manufacturers have worked to set cybersecurity standards for medical devices as well as to offer software updates and recall affected infusion pumps, the researchers said failures to implement best practices and insufficient security training for healthcare workers remain contributing factors.

In addition, “the average infusion pump has a life of eight to 10 years, which means the widespread use of legacy equipment has hampered efforts to improve security,” they wrote.More broadly, late last year the FDA alerted medtech manufacturers to the hacking risk discovered within the widely used Apache Log4j tool, which has been described as one of the largest and most critical vulnerabilities of the last decade. 

According to industry estimates, more than 90% of all enterprise cloud software environments were vulnerable to the flaw, and the agency said it may also allow an unauthorized user to remotely impact the safety and effectiveness of medical devices.

As of December 2021, no cases of patient harm had been reported to the FDA, but the agency suggested manufacturers assess and secure their own software and also evaluate any third-party systems connected to their own platforms.

https://www.fiercebiotech.com/medtech/three-four-infusion-pumps-vulnerable-cyberattacks-study

Evolus' has something to smile about as neurotoxin Jeuveau's 2021 sales swell 76%

 Cosmetic neurotoxin up-and-comer Jeuveau is giving Evolus something to smile about, thanks to record sales in the last three months of 2021. And the drug still has plenty of room to grow in a $2 billion U.S. market ruled by AbbVie’s aesthetics juggernaut Botox, analysts said Friday. 

Evolus’ Jeuveau garnered $34.7 million in the fourth quarter and $99.7 million in full-year 2021 sales, rising more than 76% over the $56.5 million it made in 2020. Evolus credited those gains to boosted sales volume and the med’s higher price point in the U.S. The company also highlighted the success of its beauty-first, millennial-targeted marketing push.

“Our strong results were driven by our singularity in focus targeting Jeuveau to millennial consumers, the fastest-growing segment of neurotoxin users, through our first in class co-branded marketing program,” David Moatazedi, president and CEO at Evolus, said in a statement. 

In 2021, the company said it ran more than 2,300 individualized co-branded marketing campaigns across the U.S., which ginned up more than 1 billion impressions for the year. “This is more than four times the number of campaigns that were run in 2020 and 20 times the number of impressions,” the company said.

Many analysts agree that Evolus’ promotional strategy is paying off. 

Evolus’ focus on millennials and the medical spa sector plus investments in co-branding with aesthetic practices “should enable Evolus to outperform the overall aesthetic neurotoxin market growth by about three-fold" this year, Mizuho Securities analysts wrote in a note to clients Friday. They forecast Jeuveau growth of 49%, versus a 16% increase across the market. 

Meanwhile, Evolus’ “co-branded initiatives are proving to be highly successful and targeted (the latest expansion of this strategy is in streaming TV) and offer a unique point of differentiation for Jeuveau,” SVB Leerink analysts wrote in a separate note. 

Jeuveau’s $99.7 million revenue is a drop in the bucket compared to the $5.23 billion AbbVie’s Botox generated worldwide in 2021, but Evolus’ drug still has ample room to grow, multiple analysts said. Based on publicly available information, Jeuveau looks to be the fastest-growing med on the cosmetic neurotoxin scene, the Mizuho Securities team said. 

Meanwhile, Botox, which was first approved way back in 1991, carries a slate of medical indications, too, including migraine and treatment of urinary incontinence. Jeuveau, which snagged its green light in 2019, is only approved on the aesthetics side.

Cantor Fitzgerald analysts, for their part, told clients they believe Jeuveau’s value proposition is “under-appreciated,” adding that they think the drug can “pick up meaningful market share in what we view as a fast-growing and highly under-penetrated market.”

The SVB Leerink team suggested Jeuveau has “significant” room to grab a bigger slice of the roughly $2 billion U.S. aesthetics pie.

Jeuveau is approaching several milestones that could boost sales in the long term. The drug’s European launch remains on track for the third quarter, and the company plans to start enrolling a phase 2 study of “extra strength” Jeuveau in Q1. Data from that trial should arrive in about a year, the SVB Leerink team pointed out. Evolus also plans to increase the med’s price this year.

The European aesthetics market is worth some 25% of the U.S.’ at about $500 million and features lower pricing, too. Nevertheless, the continent makes up the second-largest aesthetics market globally, SVB Leerink said. 

As for the rest of the year, Evolus forecasts revenues between $143 million and $150 million. That prediction, which assumes 43% to 50% growth, is “much higher than the industry growth rate of mid-teens,” the Cantor Fitzgerald team noted.

https://www.fiercepharma.com/pharma/evolus-neurotoxin-jeuveau-gives-company-something-smile-about-2021-sales-swell-76

Mouse study suggests viral infections can lead to autoimmune diseases

 Evidence is mounting that seemingly innocuous viral infections can in some cases cascade into a range of more serious diseases. In a new study in mice, researchers at Washington University in St. Louis have uncovered a mechanism by which a common childhood virus could play a role in autoimmune diseases down the track.

Viral infections are extremely common throughout our lives, with most resolving without serious issue. But recent research is increasingly showing that many of these apparently benign infections could possibly, in combination with other genetic and environmental factors, trigger diseases like Alzheimer’s, multiple sclerosis, and several types of cancer. Exactly how these viruses set off these chain reactions remains unclear, but in the new study the researchers may have uncovered one possible mechanism.

Roseolovirus is a type of herpesvirus that infects almost everyone within the first few years of life. The initial illness is usually mild, involving a rash and a fever that clears up in days, but the virus itself sticks around for a lifetime, lying dormant. While it usually doesn’t cause any symptoms after that initial infection, scientists have suspected that it may play a role in autoimmune diseases.

So for the new study, the Washington researchers investigated the link. They found that the virus seems to be able to infect the thymus, the organ where T cells mature so they can recognize foreign antigens. But the thymus also eliminates T cells that are liable to attack the body’s own cells – and it’s this latter process that the virus can disrupt. With this checkpoint weakened, more defective T cells circulate and increase the risk of autoimmune diseases.

The team uncovered this mechanism in experiments in mice. They started by infecting newborn animals with a mouse version of roseolovirus, and found that 12 weeks later, all of the mice had developed autoimmune gastritis, an inflammation of the stomach.

In other tests, the researchers treated the virus to see if that had an effect on the gastritis – when antivirals were administered over the first few days of infection, the inflammation didn’t occur. But if the drugs were given eight weeks later, it was too late to stop the gastritis from developing by the 12-week mark.

While the autoimmune problems manifested in the stomachs of the infected mice, analysis revealed that the extent of the problem ran further. The team found that the mice had not only developed antibodies against proteins on stomach cells, but to a range of other proteins throughout the body, some of which are implicated in other autoimmune diseases.

It’s important to note, however, that this study was performed on mice, with a mouse virus, and the results may not necessarily translate to humans. But the team says that the human roselovirus is very similar to that found in mice, so it at least warrants further investigation as a potential cause. Even so, it must only be one piece of the puzzle, due to how common the virus is.

“Human autoimmune disease also may occur via viral infection that gets cleared but leaves damage that can cause autoimmunity,” said Wayne Yokoyama, senior author of the study. “But if so, there has to be some other factor that we don’t understand yet that makes some people more susceptible to the autoimmune effects of roseolovirus infection, because almost all people are infected, but most people do not get autoimmune diseases. That is a really important topic for further investigation.”

The research was published in the Journal of Experimental Medicine.

Source: Washington University in St. Louis

https://newatlas.com/medical/viral-infections-autoimmune-diseases/

Young, healthy adults died from COVID-19 due to ECMO shortage

 Nearly 90 percent of COVID-19 patients who qualified for, but did not receive, ECMO (extracorporeal membrane oxygenation) due to a shortage of resources during the height of the pandemic died in the hospital, despite being young with few other health issues, according to a study published in the American Journal of Respiratory and Critical Care Medicine.

The Vanderbilt University Medical Center (VUMC) study, led by Whitney Gannon, MSN, director of Quality and Education for the Vanderbilt Extracorporeal Life Support Program (ECLS), analyzed the total number of patients referred for ECMO in one referral region between Jan. 1, 2021, and Aug. 31, 2021.

Approximately 90% of patients for whom health system capacity to provide ECMO was unavailable died in the hospital, compared to 43% mortality for patients who received ECMO, despite both groups having young age and limited comorbidities.

"Even when saving ECMO for the youngest, healthiest and sickest patients, we could only provide it to a fraction of patients who qualified for it," Gannon said. "I hope these data encourage hospitals and federal authorities to invest in the capacity to provide ECMO to more patients."

Once a patient was determined to be medically eligible to receive ECMO, a separate assessment was performed of the health system's resources to provide ECMO.

When health system resources -- equipment, personnel and intensive care unit beds -- were not available, the patient was not transferred to an ECMO center and did not receive ECMO.

Among 240 patients with COVID-19 referred for ECMO, 90 patients (37.5%) were determined to be medically eligible to receive ECMO and were included in the study. The median age was 40 years and 25 (27.8%) were female.

For 35 patients (38.9%), the health system capacity to provide ECMO at a specialized center was available; for 55 patients (61.1%), the health system capacity to provide ECMO at a specialized center was unavailable.

Death before hospital discharge occurred in 15 of the 35 patients (42.9%) who received ECMO, compared with 49 of the 55 patients (89.1%) who did not receive ECMO.

"Throughout the pandemic, it has been challenging for many outside of medicine to see the real-world impact of hospitals being 'strained' or 'overwhelmed,'" said co-author Matthew Semler, MD, assistant professor of Medicine at VUMC. "This article helps make those effects tangible. When the number of patients with COVID-19 exceeds hospital resources, young, healthy Americans die who otherwise would have lived."

In total, the risk of death for patients who received ECMO at a specialized center was approximately half of those who did not.

"Because some patients die despite receiving ECMO, there has been debate about how much benefit it provides. This study shows the answer is a huge benefit," said senior author Jonathan Casey, MD, assistant professor of Medicine at VUMC.

"This data suggests that, on average, providing ECMO to two patients will save a life and give a young person the potential to live for decades," he said.

The study was funded by NIH National Heart, Lung, and Blood Institute grants K23HL153584 and K23HL143053.

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Story Source:

Materials provided by Vanderbilt University Medical Center. Original written by Craig Boerner. Note: Content may be edited for style and length.

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Journal Reference:

1. Whitney D. Gannon, John W. Stokes, Sean A. Francois, Yatrik J. Patel, Meredith E. Pugh, Clayne Benson, Todd W Rice, Matthew Bacchetta, Matthew W Semler, Jonathan D Casey. Association Between Availability of ECMO and Mortality in COVID-19 Patients Eligible for ECMO: A Natural Experiment. American Journal of Respiratory and Critical Care Medicine, 2022; DOI: 10.1164/rccm.202110-2399LE

https://www.sciencedaily.com/releases/2022/02/220225123434.htm

People who test positive for Covid can get antiviral pills at pharmacies free, Biden says

 President Joe Biden on Tuesday said Americans who test positive for Covid-19 can receive antiviral pills for free at local pharmacies and community health centers under a new program that launches this month.

“We’re launching the ‘Test to Treat’ initiative so people can get tested at a pharmacy, and if they’re positive, receive antiviral pills on the spot at no cost,” Biden said during his State of the Union speech Tuesday.

The administration will launch hundreds of sites nationwide at CVS, Walgreens and Kroger as well as community health centers this month, a White House official said. Biden said Americans can also order more free Covid tests at the government’s website, covidtests.gov, next week. Households are eligible for four free Covid tests per order. Families are limited to two orders starting next week based on residential address.

The president said Pfizer is working to deliver 1 million courses of its Covid treatment pill, Paxlovid, this month. Paxlovid was 89% effective at preventing hospitalization among people who were at risk of developing severe illness during clinical trials.

Biden said the U.S. has reached a new moment in the pandemic, with cases of severe illness down to their lowest level since July. The omicron Covid variant upended the country in December and January, causing an unprecedented wave of infection that pushed many hospitals to the brink.

The president said most Americans are now safe to go about their lives mask free under new guidance issued by the Centers for Disease Control and Prevention last week. Biden said more of the country will also meet CDC guidelines to go mask free in the next two weeks.

 “With 75% of adult Americans fully vaccinated and hospitalizations down by 77%, most Americans can remove their masks, return to work, stay in the classroom, and move forward safely,” the president said.  

Biden said the U.S. is prepared for new Covid variants, with the ability to deploy new vaccines within 100 days if needed.

“I cannot promise a new variant won’t come. But I can promise you we’ll do everything within our power to be ready if it does,” he said.   

https://www.cnbc.com/2022/03/01/people-who-test-positive-for-covid-can-receive-antiviral-pills-at-pharmacies-for-free-biden-says.html