Agenus: optimism increasing ahead of ESMO 2020 presentation

Shares in Agenus (NASDAQ:AGEN) are rallying 23.65% at 2:10 pm EDT today ahead of a planned oral presentation of clinical trial data at the European Society of Medical Oncology (ESMO) Conference on Sept. 18, 2020.

An immuno-oncology biotech company developing compounds to help the immune system fight cancer, Agenus’ most advanced drugs in development are the anti-PD-1 targeting therapy, balstilimab, and the anti-CTLA-4 antibody, zalifrelimab.

Previously, the company announced promising results for these compounds in refractory or relapsing cervical cancer and on August 26, management said a late-breaker abstract involving these antibodies has been accepted for oral presentation at the high-profile ESMO conference.

Because oral presentations are typically reserved for particularly important discoveries, investors are optimistic that data to be announced at the conference will increase the likelihood of balstilimab and zalifrelimab securing Food and Drug Administration (FDA) approval someday. 

For perspective, early results reported so far include a 26% response rate to balstilimab and zalifrelimab combination therapy, exceeding the 10% to 15% response rate historically observed when using currently approved therapies in the second-line cervical cancer indication.

Agenus plans to initiate a rolling-FDA application for balstilimab’s approval before the end of 2020; a filing for its use in combination with zalifrelimab could follow depending on discussions with regulators.

There’s no guarantee data to be presented at ESMO will impress attendees or that the FDA will eventually sign off on these drugs, but there’s significant potential if regulators cooperate. The market for anti-PD-1 therapy is worth over $20 billion per year, and combination therapies represent a significant opportunity to improve efficacy and garner greater market share. Because Agenus is developing its own PD-1 for use alongside its anti-CTLA-4 drug, it could eventually pull in meaningful revenue, especially if the combination can be used in other larger indications.

https://www.fool.com/investing/2020/09/10/why-agenus-is-soaring-25-today/

AstraZeneca CEO Says COVID-19 Vax Trial Pause is Second Since July

In a private call with investors from J.P. Morgan late Wednesday, AstraZeneca Chief Executive Officer Pascal Soriot confirmed that a woman injected with the company’s experimental COVID-19 vaccine candidate developed a serious spinal inflammatory disorder called transverse myelitis.

The trial was paused by the U.K.-based pharma company to assess the illness and determine whether or not the vaccine was the cause. However, during that same call with investors, Soriot said this was not the first time the Phase II/III study had been halted. In July, the study was paused after another patient experienced neurological issues. According to STAT News, which first reported the call, that patients was diagnosed with multiple sclerosis and it was determined the issue had nothing to do with the company’s experimental vaccine treatment. Although STAT did not participate in the call, some who did spoke to the news outlet on condition of anonymity. The sources told the outlet that Soriot wanted to reassure the investors that AstraZeneca is taking every precaution regarding safety with the vaccine candidate.

“A vaccine that nobody wants to take is not very useful,” Soriot was reported as saying during the call.

In a statement released publicly Wednesday, Soriot said the company is putting “science, safety and the interests of society” at the center of its work. He said the temporary pause to the late-stage study is “living proof” the company is following those principles while the Independent Data Monitoring Committee assesses the patient and the potential relationship between the vaccine candidate and the development of transverse myelitis.

“We will be guided by this committee as to when the trials could restart, so that we can continue our work at the earliest opportunity to provide this vaccine broadly, equitably and at no profit during this pandemic,” Soriot said in a statement.

Transverse myelitis is an inflammation of a part of the spinal cord that can lead to pain, muscle weakness, paralysis, sensory problems, or bladder and bowel dysfunction. According to the Mayo Clinic, transverse myelitis can be caused by infections and immune system disorders. The patient who contracted the rare condition, a woman in the United Kingdom, was hospitalized for the illness, but was expected to be released this week, STAT reported.

AstraZeneca launched its Phase III trial in the United States last month. The company hopes to include up to 30,000 patients in the trial. AstraZeneca said it will expedite the review of the patient’s illness to minimize any potential impact on the timeline of the trial.

AstraZeneca’s COVID-19 vaccine candidate AZD1222 is a viral vector-based, weakened version of adenovirus containing the genetic material of SARS-CoV-2 spike protein. It was co-developed with the Jenner Institute at Oxford University. In July, the company published positive Phase I data from its vaccine candidate that showed the preventative medication generated both neutralizing antibodies and immune T-cells that target the virus that causes COVID-19.

If the vaccine makes it through regulatory trials, AstraZeneca plans to manufacture two billion doses of its vaccine, with 400 million slated for the U.S. and UK, and one billion allotted for low- and middle-income countries.

The trial was paused the same day AstraZeneca joined eight other vaccine makers in a pledge to allow science and not political expediency drive the development and potential regulatory authorization of the medication. AstraZeneca, Pfizer, BioNTech, Moderna, GlaxoSmithKline, Sanofi, Novavax, Merck and Johnson & Johnson all agreed to the promise that any vaccine candidate put forward for approval will meet the rigorous standards set forth by regulatory agencies for approval.

https://www.biospace.com/article/astrazeneca-ceo-says-vaccine-trial-pause-is-the-second-since-july/

CDC: Dining Out Tied to Coronavirus Infection

Patients with symptomatic COVID-19 were more likely than uninfected controls to report some form of restaurant dining — including indoor, patio and outdoor seating — in the 2 weeks prior to symptom onset, CDC researchers found.

Compared to controls without COVID-19, case patients were more than twice as likely to have reported dining at a restaurant (adjusted OR 2.4, 95% CI 1.5-3.8), reported Kiva Fisher, PhD, of the CDC, and colleagues.

When the analysis was restricted to case patients with close contact to anyone with confirmed COVID-19, case patients were still more likely to report having visited a bar/coffee shop (aOR 3.9, 95% CI 1.5-10.1) or restaurant (aOR 2.8, 95% CI 1.9-4.3) than control patients, albeit with wider confidence intervals, Fisher’s group wrote in the Morbidity and Mortality Weekly Report.

Not surprisingly a substantially larger proportion of case patients reported close contact with a person with COVID-19 versus controls (42% vs 14%, respectively).

This data was previewed at the National Academy of Sciences and Medicine (NASEM) workshop on airborne transmission as part of the growing “circumstantial evidence” suggesting airborne transmission may play a role in COVID-19 spread.

“Reports of exposures in restaurants have been linked to air circulation,” the authors wrote. “Direction, ventilation, and intensity of airflow might affect virus transmission, even if social distancing measures and mask use are implemented according to current guidance.”

Researchers examined data from adults tested for SARS-CoV-2 at one of 11 Influenza Vaccine Effectiveness in the Critically Ill (IVY) Network sites in July. COVID-19 cases were confirmed via PCR testing for SARS-CoV-2 from respiratory specimens. For every case, control patients who tested negative for SARS-CoV-2 were matched based on age, sex and study location. The investigators then followed up with phone interviews. After screening, Fisher and colleagues had 154 case patients and 160 controls for analysis.

Controls were significantly more likely to be non-Hispanic white, have a college degree or higher and report at least one underlying chronic medical condition compared to cases. Self-reported mask compliance was high in both groups, with 71% of cases and 74% of controls reporting always using face coverings in public. About half of close contacts reported (51%) were family members.

About half of all participants reporting going shopping or visiting someone inside of a home with 10 people or less at least once in the 14 days prior to symptom onset. However, there was no difference between cases and controls in reported shopping, gatherings in homes irrespective of the number of guests, going to an office or salon, using public transportation, patronizing a bar or coffee shop, or attending church/religious gatherings. https://tpc.googlesyndication.com/safeframe/1-0-37/html/container.html

Overall, 107 participants said they’d gone to a restaurant and 21 to a bar or coffee shop. Cases not only outnumbered controls in these groups, but were also significantly more likely to report that “almost all patrons” at the establishments weren’t wearing masks or maintaining safe distances.

“Implementing safe practices to reduce exposures to SARS-CoV-2 during on-site eating and drinking should be considered to protect customers, employees, and communities and slow the spread of COVID-19,” Fisher and colleagues concluded.

• Disclosures

Fisher disclosed no conflicts of interest.

Other co-authors disclosed support from Campbell Alliance, the NIH, the FDA, the Agency for Health Care Research and Quality, Sanofi-Pasteur, Pfizer, Merck, the Department of Defense, Marcus Foundation, Endpoint Health, Entegrion, bioMerieux, Bioscape Digital, Rapid Pathogen Screening, Inflammatix, Baxter, Cytovale, Intermountain Research and Medical Foundation, Janssen, Faron, Sedana, Asahi Kasei Pharma, Immunexpress Inc., Regeneron, Cumberland Pharmaceuticals, Inc, Avisa Pharma, LLC, and Seqirus.

Primary Source

Morbidity and Mortality Weekly Report

Source Reference: Fisher KA, et al “Community and Close Contact Exposures Associated with COVID-19 Among Symptomatic Adults ≥18 Years in 11 Outpatient Health Care Facilities — United States, July 2020” MMWR 2020; 69: 1258-64.

https://www.medpagetoday.com/infectiousdisease/covid19/88543

Public trust in CDC, Fauci, other top health officials evaporating: poll

A new poll paints a bleak picture of Americans’ views toward the coronavirus pandemic.

The poll, from the nonpartisan Kaiser Family Foundation, finds that the public’s trust in the Centers for Disease Control and Prevention and the U.S.’s top doctors, like Anthony Fauci, is rapidly dropping, particularly among Republicans. It also finds that a sizable percentage of Americans still hold a number of incorrect beliefs about the pandemic, and that less than half of Americans surveyed would want to get vaccinated against Covid-19 if a vaccine was available before November.

The poll, which was conducted from Aug. 28 to Sept. 3, provides a striking glimpse into how the U.S. government’s chaotic response to the coronavirus pandemic is sowing distrust among both Republicans and Democrats. It also reveals growing partisan divides about reliable sources of health information.

Public confidence in the CDC has dropped 16 points since April, according to the new poll. The agency has been widely criticized both by public health advocates, who want the agency to more frequently stand up to political pressure, and by Trump, who has accused it of being overly cautious and thwarting the U.S. recovery from the ongoing pandemic.

Trump’s critiques hit harder: Republicans’ confidence in the CDC has dropped 30 points since April. Democrats’ trust in the CDC has dropped less precipitously, from 86% to 74% over the same time period.

The CDC and Director Robert Redfield aren’t the only ones facing a crisis of confidence. The U.S. public’s overall trust in Fauci, the National Institutes of Health’s top infectious disease doctor, has declined 10% since April. Republicans have particularly soured on him: His favorables dropped nearly 30% among Republicans since April. Democrats’ confidence in Fauci, meanwhile, has increased from 80% to 86% since April.

The public writ large still trusts Fauci to provide reliable information more than it trusts the CDC, the White House coronavirus coordinator Deborah Birx, President Trump, or former Vice President Joe Biden, according to the new poll. Trump is the least trusted out of the four: Just 40% of those surveyed said they trust Trump to provide reliable information about the pandemic. Fifty-two percent trust Biden.

People in the U.S. also still hold a number of glaring misconceptions about the coronavirus, the KFF poll found.

More than half of Republicans surveyed still believe that hydroxychloroquine, the malaria treatment touted by Trump, is an effective treatment for Covid-19, despite a plethora of studies debunking that claim. Twenty percent of people, regardless of party,  also believe that wearing a mask is harmful for your health, despite a dearth of evidence supporting that conclusion. Fourteen percent falsely believe there is a cure for Covid-19.

The findings come amid growing concern from the American public over the politicization of the U.S. coronavirus response.

Roughly 40% of Americans surveyed in the new KFF poll said that both the FDA and CDC were paying too much attention to politics.

Sixty-two percent of Americans are also worried that the FDA will rush to approve a coronavirus vaccine due to political pressure, according to the new KFF poll. Those findings track closely with a STAT-Harris Poll survey, which found that 78% of Americans worried the Covid-19 vaccine approval process is being motivated more by politics than science.

KFF’s poll also found that a large portion of Americans would decline a vaccine if it was approved before November.

The KFF poll found that only 42% of participants surveyed would want to get vaccinated if a vaccine was approved, and offered for free, before the November election. Republicans were more skeptical about the potential vaccine than Democrats and independents: 60% of Republicans surveyed said they would not want to get the vaccine if it was approved before November.

Participants in the KFF poll were less interested in getting a vaccine than those surveyed in the STAT-Harris poll. STAT’s poll found that 62% percent of participants surveyed said they were likely to get vaccinated if a vaccine was approved before the election.

The new KFF poll comes less than two months before the election. KFF’s poll also casts doubt on the theory that the election will solely be a referendum on Trump’s response to the coronavirus pandemic.

While 36% of  Democrats said the coronavirus was the most important issue for them in the November election, just 4% of Republicans rated the pandemic as their most important issue. Swing voters rated the economy and criminal justice as more important issues than coronavirus, too.

“Democrats and Republicans are having two different elections,” KFF President Drew Altman said in a press release. “For Democrats, it’s about Covid and race. For Republicans it’s the economy and violence.”

KFF surveyed a nationally representative sample of 1,199 adults.

Public trust in CDC, Fauci, and other top health officials is evaporating, poll finds

Russia’s RDIF agrees to manufacture Covid-19 vaccine in Brazil

Russia’s sovereign wealth fund RDIF said on Thursday that it had agreed to manufacture Russia’s first registered COVID-19 vaccine “Sputnik-V” in Brazil.

RDIF, which is backing the vaccine’s development, also said it planned to supply up to 100 million doses of the vaccine to Latin America.

https://www.reuters.com/article/us-health-coronavirus-russia-brazil/russias-rdif-agrees-to-manufacture-covid-19-vaccine-in-brazil-idUSKBN2612R0

NIH launches two trials to test blood thinners in COVID-19 patients

The National Institutes of Health (NIH) said on Thursday it has launched two of the three late-stage clinical trials to test the effectiveness and safety of different types of blood thinners in treating COVID-19 among adults.

The three trials are being run under the U.S. government’s Operation Warp Speed program, which aims to speed up the development, manufacturing and distribution of vaccines, tests and drugs against the coronavirus.

Blood clotting throughout the body is one of the many life-threatening effects of the respiratory illness and can lead to other complications such as heart attack, stroke and obstruction of blood vessels in lungs, the agency said in a statement here

“There is currently no standard of care for anticoagulation in hospitalized COVID-19 patients, and there is a desperate need for clinical evidence to guide practice”, said NIH Director Francis Collins.

The agency has already begun separate trials testing blood thinners in hospitalized COVID-19 patients and those with COVID-19 who have not been admitted to a hospital.

Those who have not been hospitalized will receive either a placebo, aspirin or a low or therapeutic dose of Bristol-Myers Squibb Co (BMY.N) and Pfizer Inc’s (PFE.N) blood thinner Eliquis.

Hospitalized patients will receive varying doses of heparin to test the safety and effectiveness of the generic blood thinner in preventing clotting events, the agency said.

A third trial to start later will focus on patients discharged after hospitalization for moderate to severe COVID-19.

https://www.reuters.com/article/us-health-coronavirus-usa-bloodthinners/nih-launches-two-trials-to-test-blood-thinners-in-covid-19-patients-idUSKBN2613FQ

Influenza may facilitate the spread of SARS-CoV-2

View ORCID ProfileMatthieu Domenech de Celles, View ORCID ProfileJean-Sebastien Casalegno, View ORCID ProfileBruno Lina, View ORCID ProfileLulla Opatowski

doi: https://doi.org/10.1101/2020.09.07.20189779

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2020.09.07.20189779v1.full.pdf

Abstract

As in past pandemics, co-circulating pathogens may play a role in the epidemiology of coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we hypothesized that influenza interacted with SARS-CoV-2 during the early 2020 epidemic of COVID-19 in Europe. We developed a population-based model of SARS-CoV-2 transmission, combined with mortality incidence data in four European countries, to test a range of assumptions about the impact of influenza. We found consistent evidence for a 2-2.5-fold population-level increase in SARS-CoV-2 transmission associated with influenza during the period of co-circulation. These results suggest the need to increase vaccination against influenza, not only to reduce the burden due to influenza viruses, but also to counteract their facilitatory impact on SARS-CoV-2.

Competing Interest Statement

MDdC received postdoctoral funding (2017-2019) from Pfizer and consulting fees from GSK. JSC declares no competing interests. BL is chair of the ISC for the Global Influenza Surveillance Network, and co-chair of the Global Influenza and RSV initiative; he is also a member of the French COVID-19 Scientific Committee (no personal income for all these activities). LO has received consulting fees from WHO for work on antimicrobial resistance.

Funding Statement

No specific funding was used for this study.

https://www.medrxiv.org/content/10.1101/2020.09.07.20189779v1