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Thursday, April 8, 2021

Biden officials rebuff appeals to surge Covid-19 vaccine to Michigan amid growing crisis

 Amid Michigan’s worst-in-the-nation coronavirus surge, scientists and public health officials are urging the Biden administration to flood the state with additional vaccine doses.

So far, though, their plea has fallen on deaf ears. Instead, the federal government is sticking to a vaccine-allocation strategy that largely awards doses to states and territories based on their population. As a result, most jurisdictions are still receiving similar per-capita vaccine supplies, regardless of how many people there are getting sick — or how many excess vaccine doses they have. 

Experts have cast a surge in Michigan’s vaccine supply as a critical tool in combating the state’s most recent Covid-19 crisis. The state is currently recording nearly 7,000 new cases per day, just shy of its all-time peak in December. Hospitalizations and deaths, which tend to lag a few weeks behind increasing case counts, are also on the rise. 

“I would be surging a lot of vaccines to Michigan right now,” said Ashish Jha, the dean of the Brown University School of Public Health. “To me, this is a no-brainer policy, and I would be curious to hear why the Biden team hasn’t done this.” 

During a media briefing on Wednesday, White House officials acknowledged that Michigan’s situation is dire. They gave no indication, though, that they would send additional vaccines there to help quell the surge, when STAT asked. They argued that it is too early in the national vaccine campaign to begin targeting supply based on case rates. 

Rochelle Walensky, the director of the Centers for Disease Control and Prevention, said the agency was working to expand testing capacity in the state, address outbreaks in Michigan’s jails and prisons, and scale up genomic sequencing. The one strategy she did not bring up was scaling up vaccine supply. 

“By and large, we are still allocating vaccines based upon population,” Andy Slavitt, one of President Biden’s top pandemic-response advisers, said during the briefing. “Clearly we will get to a place where more targeted strategies will work, but right now I would commit to you that we’re doing both.” 

The administration’s fixed position is at odds with public health experts like former Food and Drug Administration commissioner Scott Gottlieb; the physician-researcher Eric Topol; and the Flint, Mich.-based public health advocate Mona Hanna-Attisha

Some have attempted to quantify what’s at stake more precisely: One modeler, University of California, Berkeley, research programmer Joshua Schwab, projected recently that doubling Michigan’s vaccine allocation for two weeks could help prevent 10,000 hospitalizations and 1,200 deaths. 

The state’s Democratic governor, Gretchen Whitmer, first asked President Biden for additional vaccine supplies on March 30. But Jeff Zients, the White House’s Covid-19 response coordinator, rebuffed the request, the Washington Post reported.  

“I know that some national public health experts have suggested this as an effective mitigation tool, and I know we’d certainly welcome this approach in our state,” Whitmer reportedly said on a call between governors and Biden administration advisers. 

Instead, White House and CDC officials are working with Michigan to leverage its existing vaccine supply and potentially surge shipments within the state. 

Despite his resistance to increasing the number of doses Michigan received, Slavitt stressed that the federal vaccine effort is not a one-size-fits-all endeavor. 

As examples, he stressed that the Biden administration was now allowing community health centers to order vaccines directly; adding locations to the government’s retail pharmacy partnership “surgically”; and locating federal vaccination sites in the places determined to be most in need. 

“I wouldn’t want to give the impression that we are — someone is sitting back and managing this pandemic according to some formula,” Slavitt said. “It’s not true in the least.”

To date, the White House’s population-based system for determining vaccine supply has faced little pushback or criticism, even though states have experienced different rates of Covid-19 spread for months. 

Broadly, the federal vaccination effort is viewed as a major success. The U.S. is currently administering roughly 3 million vaccine doses per day. Nearly one-third of the country, and more than three-quarters of all older adults, have received at least one vaccine dose. 

Biden announced on Tuesday that he would direct states to open vaccine eligibility to all adults by April 19, almost two weeks earlier than his prior goal of May 1. Many states, including Michigan, had already done so. 

Even as the broader vaccination campaign continues to accelerate, however, momentum has built for surging vaccines to hot spots. The debate in Michigan mirrors one in New Jersey, which experts have argued should also receive additional vaccine supply. Federal officials have similarly ignored that request. 

Four months into the U.S. vaccination effort, though, vaccine supply is far less tight. 

“There are states like Alabama, Georgia, Mississippi, Louisiana, Utah, where throughout much of the day, the vaccine appointments are going unfilled,” Jha said. “What all of us are arguing for is, for the next couple weeks, surge a ton of vaccines to Michigan. And if certain states that have plenty of supply get a 25% lower allotment for two weeks, they probably won’t miss it. Then, get them back to their normal level, and catch them up if they need it.”

https://www.statnews.com/2021/04/08/michigan-covid-surge-biden-officials-no-additional-vaccine-doses/

In Covid-19 vaccine push, no one speaking Gen Z’s language

 Useful Covid-19 information isn’t reaching the Instagram generation.

There’s almost no messaging specifically tailored to them from federal or state public health officials. There’s hardly anything official on Tik Tok. And even the limited efforts to reach them where they are — like Instagram’s links to its “Covid-19 information center”— aren’t working.

Just ask Kymon Palau, a 21-year-old from Albuquerque, N.M., who has over 18,000 followers on the site.

“If I am being honest with you, I probably clicked those tags once back in April of last year and never clicked them again — it’s annoying,” Palau said.

Palau isn’t alone — in interviews with more than half a dozen other young people around the country, nearly all said they weren’t opposed to vaccinations — they just couldn’t find information tailored to them.

That lack of information is clearly having an impact. A recent STAT-Harris Poll finds that 21% of Generation Z — defined in the survey as young adults aged 18 to 24 — said they would not get vaccinated against Covid-19 and another 34% said they would “wait awhile and see” before getting vaccinated. The results come on the heels of an NBC-Morning Consult poll that found that 26% of Gen Z said they would not get the vaccine.

“There isn’t anything that is consumable and/or targeted at our demographic,” said Gabrielle Kalisz, a 22-year-old who lives in Washington, D.C., and who has been vaccinated. “All the messaging online … isn’t targeted toward our age group, it doesn’t explain why, if you’re a healthy 19-year-old, you should get this vaccine.”

Numerous public health officials told STAT that the issue of growing vaccine reluctance among young people can be solved with a coordinated campaign of reliable, useful information that makes it both easy and enticing for young people to get vaccinated, even if they may not personally benefit much.

Those same officials acknowledged, however, that much of the groundwork for messaging to young people is yet to be done.

Time is running out: Unvaccinated young people are fueling an exponential uptick in Covid-19 cases in the Midwest, prompting fears of a fourth Covid-19 surge that could spread throughout the United States. Around the world, young people are also increasingly showing up in intensive care units with life-threatening symptoms. The uptick in cases, which experts believe is caused by the increased spread of the coronavirus variant known as B.1.1.7, has been so serious that it has prompted one Canadian province to go back into lockdown. Public health officials also fear that reopening universities this fall could fuel regional outbreaks in college towns around the country.

“People keep referring to it as the race against time, but that’s where we are,” Michael Meit, a researcher who holds positions at the University of Chicago and East Tennessee State University’s Center for Rural Health Research. “We need to get as many people vaccinated as quickly as possible and in particular we need to get the people vaccinated who are the ones who are spreading the virus, and right now the people who are spreading the virus are those younger age groups.”

Catriona Fee, 19, from Washington, D.C., isn’t getting vaccinated. She’s too worried about whether the Pfizer and Moderna shots will impact her ability to have a family down the line — a concern that several other Gen Zers shared with STAT. (Early data has shown that the vaccines do not affect fertility, and leading medical associations still recommend vaccines for individuals who are pregnant or plan to become pregnant.)

Fee maintains she’d be open to getting vaccinated if more information was available about potential long-term impacts on fertility, but right now she’s not convinced.

“Gen Z … they have to consider, is this going to impact my choices down the road?” Fee said. “For the vaccine, it’s, is this going to impact my ability to have children?’”

Young people are also worried about whether vaccine side effects will keep them out of work or make it harder for them to finish their mountains of homework. While all three vaccines authorized by the Food and Drug Administration have a tendency to hit young people harder with side effects, there’s little information available about what they can expect.

“People just don’t have time to try to find an appointment, to take the time out of their day to go get the shot, and have two days where they feel awful,” said Kyler Tipton, 24, of Conway, Ark., who wants to get vaccinated. “I know nobody really has the time to leave work or take a couple off of days off because they got a vaccine, but for people my age, they might miss their rent.”

They’re also just less motivated than many older people.

“The challenge in this age group is they know that the risk to them is pretty low from this virus — we shouldn’t be dishonest about that. It’s helping them be motivated enough to protect others … to overcome their own personal ambivalence,” said Sarah Van Orman, division chief of college health at the University of Southern California.

The problem of vaccine hesitancy is even more pronounced in rural, conservative communities. Recent polling suggests between 20% and roughly 40% of rural Americans are unsure about getting vaccinated.

Tipton told STAT that young people in his community are weighing the modest benefits of getting vaccinated with the criticism they may receive from their community, from people who are themselves hesitant or opposed to the vaccines.

“They just don’t see it … being more valuable than the social ostracism, and the sickness,” explained Tipton, referring to the potential side effects of the vaccine.

Though public health officials haven’t launched any specific campaigns targeting young people, Gen Zers themselves are starting to organize to help their peers.

Palau, the Instagram influencer, largely credits his own change of heart on the vaccine to his followers and fellow influencers — particularly people of color — on platforms like Instagram and TikTok. Palau, who is Indigenous, was hesitant for months because of the long history of exploitation and medical experimentation on Native communities, he said, even though he lost several family members to Covid-19.

“We were treated like lab rats to be forcibly tested on,” he said. “Of course that history is going to cross our minds.”

Eventually he made his own TikTok videos urging other Native young people to get vaccinated. His video is part of a campaign dubbed “See Friends Again,” a small campaign stood up by Bigtent Creative, an advocacy organization focused on mobilizing young people on channels like TikTok and Snapchat. The campaign focuses on contracting with young people of color who are “micro influencers” to share vaccine positive messages on their social media accounts.

Jordan Tralins, a 19-year-old from St. Petersburg, Fla., started the Covid Campus Coalition at her college, Cornell University. The campaign, which shares eye-catching, university-themed infographics answering common vaccine questions, piggybacks on the growing trend of Instagram infographic activism. More than 20 universities have now joined the coalition, including Ohio State and Notre Dame.

“I hadn’t seen any type of campaign targeted toward people my age … and that’s how the idea came to be,” explained Tralins. “I definitely don’t think the information was in my face. It was not in my Instagram feed anywhere. Anything that was on Facebook or TikTok that I saw was false information.”

Kaelin Connor, a 21-year-old from Belton, Texas, wrote an op-ed in her college newspaper debunking common vaccine myths. Kalisz, the 22-year-old from Washington, D.C., meanwhile, said she was pushing her friends to come to her for help.

“We went into the group chat and said what are your questions about the vaccine? What can I explain for you? What resources can I get to you? Can I help you find where to get vaccinated?” explained Kalisz. “A lot of it was just pushing a topic that maybe some kids didn’t even want to talk about, so that at least it was out there and we could have the conversation.”

Those kinds of personal conversations between trusted friends can make a big impact in changing peoples’ minds. Alison Buttenheim, an associate professor of nursing and health policy at the University of Pennsylvania who researches strategies to increase vaccine acceptance, described the impact of these conversations as “huge, huge, huge, huge.”


The Biden administration has promised that it’s about to get much more involved in drumming up demand for vaccines — and young people are one of its primary targets.

Last month, the Centers for Disease Control and Prevention announced a $3 billion initiative aimed at increasing vaccine acceptance. The administration also launched a sweeping public relations campaign, which includes a new “Covid community corps,” a coalition of several hundred groups that will work with the White House to spread vaccine positive messages.

Both individuals and groups can join the community corps, which will provide participating groups with resources like fact sheets and social media posts to share, although it’s not yet clear how central a role the community corp will play in the overall vaccine rollout.

NextGen America, a nonprofit that typically focuses on registering and mobilizing young voters, is a member of the new corps. The group is planning to send text alerts and emails to its some 10 million young people, both to help them figure out where to be vaccinated and to answer basic questions.

“We are hearing from folks that they are not worried about the vaccine, or it’s more important for their grandparents to get vaccinated, or they don’t know where to get vaccinated, they don’t know when they’ll be able to get vaccinated,” said Justin Atkins, the group’s national politics manager. “We have young folks that still believe they can’t get vaccinated because it’s something that’s reserved only for the elderly … in areas where they can get vaccinated.”

The community corps model concept makes sense, argued Buttenheim, the vaccine acceptance expert.

“This really seems to me like the sweet spot,” she said, adding that community-based efforts, like a recent ad promoting vaccination in New Orleans, “just land in a way that Dr. [Jill] Biden smiling and saying we should all get vaccinated probably wouldn’t.” (Buttenheim added that Biden should continue to do those, too.)

She just wishes it started sooner.

“Easy for me to say: It feels a little late,” Buttenheim said. “But that’s OK.”

number of public health officials told STAT that the reopening of college campuses may be, paradoxically, a boon for controlling Covid-19 because campuses have a leg up in helping vaccinate their populations.

“We know where people live, we know their email addresses, and we also know a lot about them. … We know how to reach different parts of our students with the messages they need,” explained Van Orman, the USC professor.

Already a handful of college campuses, including Rutgers University and Cornell University, have also mandated students get vaccinated, and others are likely to follow.

The optimism may be misplaced, especially if most universities don’t mandate the vaccine. Flu vaccination on college campuses rates typically hover between 8% and 39% — far short of the 70% recommended by the Department of Health and Human Services.

The problem is even more pressing for the roughly one-third of college-aged people who aren’t enrolled in college. While colleges can bombard their students with vaccine positive messages, create vaccine sites all over campus, and even mandate vaccines — none of that exists for those who don’t enroll in higher education.

“We have all the factors that we have in college students without the role of the institution helping to mitigate them,” said Van Orman. “I worry much more about our young adults that are not associated with institutions of higher education.”

Some public health officials are already lamenting their lack of planning, and worrying about the future.

“I’m not entirely sure how well-prepared everybody is to start communicating, getting key messages tailored to the younger generations out there. … Everybody’s been so preoccupied … they really haven’t had a chance to think two or three moves ahead,” said William Schaffner, a professor of medicine at Vanderbilt University. “We have a lot of work to do.”

Others, however, are still hopeful — they have to be.

“Using messages and strategies and approaches that are rooted in the research and that we know work will get us where we need to be,” said Ann Christiano, the director of the University of Florida’s Center for Public Interest Communications. “If I didn’t believe that, I wouldn’t be able to get out of bed in the morning.”

https://www.statnews.com/2021/04/08/gen-z-hesitant-covid-19-vaccine/

Aprea Acute Myeloid Leukemia Med Tagged Orphan Drug

 Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing and commercializing novel cancer therapeutics that reactivate the mutant tumor suppressor protein, p53, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug designation to eprenetapopt for treatment of AML.

“We are pleased to have been granted Orphan Drug designation by FDA for eprenetapopt in AML, building on the Fast Track designation in AML that was granted in November 2020,” said Christian S. Schade, Chairman and Chief Executive Officer of Aprea. “We look forward to continued productive dialogue with FDA and bringing eprenetapopt to patients as soon as possible.”

https://finance.yahoo.com/news/aprea-therapeutics-receives-fda-orphan-151500659.html

Novartis taps Artios for targets to enhance radioligand drugs

 Novartis has struck a deal with Artios Pharma to access DNA damage response (DDR) targets with the potential to enhance its radioligand therapies. Artios, which is run by some of the people behind pioneering DDR drug Lynparza, is set to get $20 million upfront and up to $1.3 billion in milestones in return for the targets.

During the three-year collaboration, Artios and Novartis will discover and validate up to three targets for exclusive worldwide use by the Swiss Big Pharma company. The goal is to find targets that add to the potential of Novartis’ radioligand therapies.

Cancer cells are prone to DNA damage because of the speed at which they replicate but there are fundamental DNA repair mechanisms that fix the problems. Some of the repair mechanisms can be upregulated in cancer cells. Radioligands and certain other therapies work by damaging DNA. If the DNA damage hits a pathway that is upregulated, then you get resistance. 

Artios is working to understand the DNA repair factors that are important to Novartis’ radioligands to discover DDR targets that enhance their efficacy. “Are there targets that if we knock out those DNA repair factors [and] processes that we would enhance in certain tumors ... the effectiveness of these radioligands? It's a combination of two things coming together ... and really sensitizing the tumor better to that style of damage,” Artios CEO Niall Martin said.

Novartis has built up its radiopharmaceutical business in recent years through in-house investment and the acquisitions of Advanced Accelerator Applications and Endocyte for, respectively, $3.9 billion and $2.1 billion. The strategy is beginning to bear fruit, with Novartis reporting last month that the drug at the heart of the Endocyte buyout had hit the mark in a phase 3 prostate cancer trial.

Other research groups see DDR and radiopharmaceuticals as complementary approaches. DDR drugs such as AstraZeneca’s Lynparza work by stopping an enzyme from repairing breaks in DNA. As such, DNA-damaging agents, such as radioligand therapy, could combine well with DDR therapies.

That thinking has led to studies that are evaluating the effects of giving radium Ra 223 dichloride in combination with the PARP inhibitors Lynparza and GlaxoSmithKline’s Zejula. PARP inhibitors put the DDR space on the map but Artios is founded on the belief there are rich pickings beyond that first, concept-validating target.

Artios’ C-suite features Niall Martin and Graeme Smith, both of who worked on Lynparza at KuDOS Pharmaceuticals. AstraZeneca bought KuDOS for $210 million but Martin and Smith both retained an interest in DDR. Martin took up the Artios CEO post in 2016 and Smith, after a stint at AstraZeneca, joined as chief scientific officer the next year.

The appointments positioned Martin and Smith to work on inhibitors of DDR enzymes beyond PARP, including DNA polymerase theta and DNA nucleases. Artios’ expertise in the area attracted Novartis Venture Fund, which contributed to a $84 million series B round, in 2018 and has now led to a deal with the Swiss Big Pharma itself.

In a statement, Martin said the collaboration “is an ideal fit” as it “maximizes the application of our platform to areas beyond our current focus as we independently advance our pipeline of novel DDR candidates.” Artios retains full control of its ATR inhibitor ART0380 and pol theta prospect ART4215.

The deal comes a few months after Merck KGaA committed to $30 million in upfront and near-term payments to work with Artios on compounds against up to eight targets. Merck is on the hook for up to $860 million in milestones per target.  

https://www.fiercebiotech.com/biotech/novartis-taps-artios-for-targets-to-enhance-radioligand-drugs

Biogen Licenses Actemra Biosimilar Candidate From Bio-Thera Solutions

 Biogen Inc. Thursday said it signed a license agreement with Bio-Thera Solutions Ltd. to develop, manufacture and commercialize Bio-Thera's BAT1806, a proposed biosimilar to Roche Holdings AG's blockbuster rheumatoid-arthritis drug Actemra.

Biogen said it will make an upfront payment of $30 million to Guangzhou, China, biopharmaceutical company Bio-Thera, contingent upon a Phase 3 study of BAT1806 achieving satisfactory results.

The Cambridge, Mass., biopharmaceutical company said it will gain exclusive regulatory, manufacturing and commercial rights to BAT1806 in all countries excluding China, while Bio-Thera will be eligible for potential milestone payments, along with royalties on sales.

Biosimilars are near-copies of biologic drugs, such as Actemra, that are made from living cells and are analogous to generic copies of traditional pill-form medicines. Worldwide sales of Actemra topped $3 billion last year.

Biogen said it expects to complete the transaction in the second quarter.

https://www.marketscreener.com/quote/stock/BIOGEN-INC-4853/news/Biogen-Licenses-Actemra-Biosimilar-Candidate-From-Bio-Thera-Solutions-32915889/

Immutep Efti, for Recurrent/Metastatic Head & Neck Cancer, Fast-Tracked

 

  • Fast Track designation opens the potential for expedited development and review with the US FDA
  • Fast Track was granted based on the promising data package from Immutep, including from Immutep’s Phase II TACTI-002 trial (Keynote-798) in head and neck squamous cell carcinoma (HNSCC)
  • Start-up preparations for Immutep’s new Phase IIb TACTI-003 trial in 1st line HNSCC are advancing well

Vir New Research Details Novel Mechanisms by Which SARS-CoV-2 Enters Host Cells

 – Growing body of evidence suggests monoclonal antibodies that target a conserved epitope have the potential to be highly effective against SARS-CoV-2 and associated known mutations –

– Newly identified cell surface proteins play a role in SARS-CoV-2 infection and determine how certain classes of antibodies work –

Vir Biotechnology, Inc. (Nasdaq: VIR) today announced the publication of new preclinical research highlighting novel mechanisms by which SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) enters host cells and identifying how auxiliary receptors may impact the clinical efficacy of monoclonal antibodies (mAbs). The research highlights the distinct mechanism of action of non-receptor-binding motif (RBM)-targeting antibodies, such as VIR-7831 and VIR-7832, the Company’s investigational SARS-CoV-2 mAbs that target a conserved non-RBM site within the receptor binding domain (RBD).

While prior literature has shown that SARS-CoV-2 infection is mediated by the virus binding to the ACE-2 entry receptor, findings from this research, posted on BioRxiv, highlight the importance of three additional auxiliary receptors that enhance infection mediated by the ACE-2 receptor. This new study addresses the role of DC-SIGN and L-SIGN lectins in infection and further identifies the SIGLEC1 lectin as a new participant in infection. SIGLEC1 is of particular importance because it is highly expressed and associated with SARS-CoV-2 in macrophages – an inflammatory cell type that is prominent in the lungs of patients with severe COVID-19. These cells can bind to infectious SARS-CoV-2 and present the virus to another cell to establish infection in that second cell. These auxiliary receptors also play an important role in modulating the neutralizing activity of different classes of spike-specific antibodies and may contribute to viral dissemination in the most severe COVID-19 cases.

This study addresses another important aspect related to the influence of the experimental methods used in measuring the neutralizing activity of different classes of spike-specific antibodies. Cells that overexpress ACE-2 at levels in excess of normal cells are widely used in neutralization assays because they can be infected with high efficiency. While these cell lines effectively measure the neutralizing activity of antibodies that target the RBM of the SARS-CoV-2 spike protein, they inadequately measure the neutralizing activity of non-RBM antibodies, as well as antibodies that target the N-terminal domain (NTD) of the spike. The NTD is a major target of human immunity to SARS-CoV-2. This observation indicates the significant limitations of the use of cells overexpressing ACE-2 for studies of mAbs and measuring serum neutralizing antibodies elicited by vaccination or infection.

https://www.globenewswire.com/news-release/2021/04/08/2206718/0/en/Vir-Biotechnology-Announces-New-Research-Demonstrating-Novel-Mechanisms-by-Which-SARS-CoV-2-Enters-Host-Cells.html