AstraZeneca seeks U.S. authorisation of drug to prevent COVID-19

 AstraZeneca has requested emergency use authorisation from U.S. regulators for its new treatment to prevent COVID-19 for people who respond poorly to vaccines because of a weakened immune system.

In a statement on Tuesday, the Anglo-Swedish drugmaker said it included data in its filing with the Food and Drug Administration from a late-stage trial that showed the drug reduced the risk of people developing any COVID-19 symptoms by 77%.

The antibody therapy called AZD7442 could protect people who do not have a strong enough immune response to COVID-19 vaccines or to supplement a vaccination course for those, such as military personnel, who need to booster their protection further, AstraZeneca has said.

While vaccines rely on an intact immune system to develop targeted antibodies and infection-fighting cells, AZD7442 contains lab-made antibodies designed to linger in the body for months to contain the virus in case of an infection.

A U.S. authorisation for AZD7442 - based on two antibodies discovered by Vanderbilt University Medical Center in the United States - could be a major win for AstraZeneca, whose widely used COVID-19 vaccine has yet to be approved by U.S. authorities.

Talks regarding supply agreements for AZD7442 are ongoing with the United States and other governments, AstraZeneca said.

COVID-19 therapies based on the same class of monoclonal antibodies are being developed by rivals Regeneron, Eli Lilly and GlaxoSmithKline with partner Vir , competing for a role in COVID-19 treatment and prevention. But Astra's filing has cemented its lead in prevention.

That contrasts with delays in Astra's quest for approval for its COVID-19 vaccine Vaxzevria in the United States, where the vast majority of those willing to get immunised have received shots from the Pfizer-BioNTech alliance, Moderna or Johnson & Johnson.

Astra said in July it expected to seek U.S. approval for the vaccine in the second half of this year.

Trial results on the AZD7442 therapy, first published in August, were taken three months after injection but the company hopes it can tout the shot as a year-long shield as trial investigators will follow up with participants as far out as 15 months.

https://finance.yahoo.com/news/1-astrazeneca-seeks-u-authorisation-064211315.html

Almost 1 in 5 health care workers quit their jobs during COVID-19: poll

 Nearly 1 in 5 health care workers reported that they have quit their job during the COVID-19 pandemic. 

A poll of 1,000 health care workers, which was conducted Sept. 2-8 by Morning Consult, showed that 18 percent of medical workers polled quit their jobs during the pandemic. Additionally, 31 percent reported that they had at least thought about leaving their work.

The workers cited issues like poor pay, pandemic-related safety fears and burnout as the reasons for their departure, according to Morning Consult. 

Experts say these departures could have a detrimental impact on the medical system. 

"You’re experiencing loss of manpower in a field that was already short on manpower before the pandemic hit," Dharam Kaushik, a urologist at the University of Texas Health, San Antonio, said to Morning Consult. 

Over half of health care workers polled said their mental health worsened in the pandemic, and 42 percent said their daily lives have suffered during COVID-19.

Morning Consult added that some of the workers surveyed said they would tell new trainees coming into the field that "patients are becoming increasingly violent and rude" while another said "don't do it unless you have a death wish."

Some respondents voiced more optimism in their advice to newcomers, saying "hang in there" and "keep patients at the focus of your practice." 

Despite those who have chosen to leave the field, the survey indicated that the majority of health care workers were optimistic about the future of their industry.

Overall, 57 percent of health care workers surveyed had positive thoughts about health care's future, the poll said.

A gender divide existed in the outlooks about health care's future with 69 percent of men expressing a positive sentiment compared to 54 percent of women, the poll said. 

Kate McOwen, senior director of educational affairs at the Association of American Medical Colleges, attributed less positive outlooks of female medical workers to increased child care responsibilities that fell on them during the pandemic, as well as the mostly white, male "power brokers" in the health care field, Morning Consult said.

“I think mentoring the next generation, and then changing our hiring practices to put women and people of color in leadership positions, it has to happen in order to address these kinds of disparities that are still present in our field,” McOwen said to Morning Consult.

https://thehill.com/policy/healthcare/575209-almost-1-in-5-healthcare-workers-quit-jobs-during-pandemic-poll

Variants likely not the main reason for booster shots: study

 A decline in the effectiveness of the Pfizer COVID-19 vaccine (Comirnaty) against infection appeared to be due to waning immunity, not the Delta variant, researchers found.

Examining sequenced infections, protection against infection with the Delta variant was 93% (95% CI 85-97) for the first month following full vaccination but then dropped to 53% (95% CI 39-65) after 4 months, reported Sara Tartof, MD, of Kaiser Permanente Southern California in Pasadena, and colleagues.

That drop was comparable in the larger cohort, where the vaccine was 88% effective against infection (95% CI 86-89) after the first month but dropped to 47% (95% CI 43-51) after 5 months, the authors wrote in The Lancet.

The vaccine was also still effective at preventing COVID-related hospitalizations due to the Delta variant, with 93% effectiveness (95% CI 84-96) for up to 6 months, they noted.

"Protection against infection does decline in the months following a second dose," Tartof said in a statement. "While this study provides evidence that immunity wanes for all age groups that received the vaccine, the CDC Advisory Committee on Immunization Practices [ACIP] has called for additional research to determine if booster shots should be made available to all age groups eligible for this vaccine."

The statement added that this research confirms "preliminary reports" from both Israel and the CDC.

CDC currently recommends a booster dose of Pfizer vaccine for certain adults initially vaccinated with Pfizer, including all adults age 65 and up, those ages 50-64 with high-risk medical conditions. It says 18- to 49-year-olds with high-risk medical conditions and adults 18-64 with high occupational or institutional risk may receive boosters, as well.

The authors examined electronic health records from December 14, 2020, to August 8, 2021, in the Kaiser Permanente Southern California health system for individuals ages 12 and up. Participants had at least 1 year of prior membership in the health system.

Overall, they assessed 3,436,957 individuals, with a median age of 45. About 52% were female and 41% were Hispanic, 32% were white, and 12% were Asian or Pacific Islander. About 2.2% tested positive for SARS-CoV-2 via RT-PCR at least once prior to the study period.

About 5% of participants were infected with SARS-CoV-2 during the study period, and of those, about 7% were admitted to the hospital, the authors noted. They added that a higher proportion of those admitted to the hospital were older, men, had comorbidities and prior increased healthcare utilization.

As of August 8, about 1 million participants were fully vaccinated with the Pfizer vaccine. The overall vaccine effectiveness over the course of the study was 73% (95% CI 72-74) and effectiveness against COVID-related hospitalization was 90% (95% CI 89-92).

There were also 8,911 specimens submitted for genomic sequencing beginning on March 4, 2021, and 5,088 (52%) with a sequence determined, the authors noted. Notably, the Delta variant increased in prevalence from 0.6% of sequenced specimens in April 2021 to 87% of sequenced specimens in July 2021.

"Along with other emerging evidence, our results suggest that despite early effectiveness of [Pfizer vaccine] against delta and other variants of concern, effectiveness against infection erodes steadily in the months after receipt of the second dose," the authors wrote.

Limitations to the data include an inability to establish causation between vaccination and COVID-19 outcomes, as this was an observational study. There was also no data about adherence to public health interventions, and genomic sequencing was "more likely to fail in samples from vaccinated individuals due to lower viral loads," which could overestimate variant-specific effectiveness, they said.

Disclosures

The study was supported by Pfizer.

Tartof disclosed support from Pfizer, Gilead, GlaxoSmithKline, and Genentech.

Other co-authors disclosed various ties to industry, including being employed by Pfizer.

Primary Source

The Lancet

Source Reference: Tartof SY, et al "Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study" Lancet 2021; DOI: 10.1016/S0140-6736(21)02183-8.

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/94841

Preprint study that miscalculated higher heart inflammation risk for mRNA vaccines retracted

In the past few weeks, anti-vaxxers have rallied behind a nonpeer-reviewed study by a group of Canadian researchers as evidence against COVID-19 vaccines. Turns out, the paper made a fatal mistake in reaching its conclusion.

Scientists at The University of Ottawa Heart Institute have retracted the preprint study, which falsely calculated a 1 in 1,000 risk of heart inflammation for Moderna's and Pfizer-BioNTech's mRNA COVID vaccines.

The study authors have withdrawn the manuscript “because of a major error pertaining to the quoted incidence data,” the team said in a retraction statement on Sept. 24.

For the research, the team collected two months of data from the Public Health Agency of Ottawa on people who had received an mRNA COVID-19 shot and calculated the incidence of myocarditis or pericarditis—inflammation of the heart muscle or the heart’s membrane—within one month after vaccination.

In the original paper, published on the preprint site medRxiv on Sept. 16, they identified 32 patients with the heart problem and 32,379 doses administered in total, leading to an estimated 1 in 1,000 rate.

However, the actual number of administered doses during the period was over 800,000, the researchers note in their retraction statement. That would put the correct incidence rate at about 1 in 25,000, or 4 in 100,000. A recent peer-reviewed study based on data in Israel has put the risk of myocarditis for Pfizer and BioNTech’s Comirnaty at 2.7 events per 100,000 persons.

In its short life on the medRxiv site, the study with the wrong data was retweeted over 15,000 times, according to Almetric.

Preprints are set up as a way for scientists to share early information on research findings. But critics have been pointing to the lack of the rigorous peer-review process, which could pick out such flaws.

The U.S. FDA in June added a warning about the rare risk of heart inflammation in the fact sheets for Pfizer-BioNTech’s and Moderna’s COVID-19 vaccines. At the time, the combined heart inflammation cases for the two mRNA vaccines were 12.6 per million doses, according to the CDC. The side effect is believed to affect males under the age of 30 more than other populations.

Noting the heart inflammation problem is very rare, the CDC has concluded that the benefits of the vaccine outweigh these risks and continues to recommend that everyone aged 12 years and older get vaccinated.

https://www.fiercepharma.com/pharma/researchers-retract-viral-preprint-study-falsely-linked-high-risk-heart-inflammation-to

Enanta pulls plug on NASH, seeks to offload assets for combos

 Enanta Pharmaceuticals is tearing up its nonalcoholic steatohepatitis (NASH) strategy. After getting a look at interim phase 2b data, the biotech has decided to stop the monotherapy trial and seek to outlicense its candidates for use in combinations. 

Massachusetts-based Enanta has two NASH candidates, EDP-305 and EDP-297, in the clinic. Both drugs are FXR agonists, the same mechanism of action of Intercept Pharmaceuticals’ obeticholic acid, with the differences limited to changes designed to improve the potency and tissue targeting of the follow-up candidate EDP-297.

Neither candidate has done enough to persuade Enanta to continue internal development. Enanta is stopping the phase 2b trial of EDP-305 that it began last year after an interim analysis of the 12-week data. 

Enanta had the option to switch its focus to its follow-up candidate. However, with a phase 1 clinical trial suggesting it is “not substantially differentiated” from EDP-305, Enanta has opted against making EDP-297 its priority. The phase 1 study “found the overall balance of activity and tolerability was comparable to that of EDP-305.” 

The data drops have persuaded Enanta to abandon internal development of the candidates. Enanta is hoping another company sees promise in the prospects, though, specifically in combination with other NASH treatments. 

“We believe that the multiple mechanisms in development for NASH today, which reflect the complex pathophysiology of this disease, make it likely that a combination approach with FXR agonists will ultimately provide the optimal treatment regimen for patients,” Enanta CEO Jay Luly, Ph.D., said in a statement. Luly sees EDP-305 and EDP-297 as well positioned to play a role in combinations. 

The rethink follows the FDA’s rejection of Intercept’s rival FXR agonist. When Enanta began its phase 2b, Intercept looked to be closing in on FDA approval. The question at that stage was whether Enanta could differentiate EDP-305 from its more advanced rival. Months later, Intercept’s rejection by the FDA raised the question of whether Enanta could get EDP-305 approved at all. Intercept is continuing to plug away at finding a route to market, but Enanta has decided to pull out and focus its energies on treatments for diseases including hepatitis B. 

https://www.fiercebiotech.com/biotech/enanta-pulls-plug-nash-seeks-to-offload-assets-for-combos

FDA greenlights combination at-home test for COVID and flu in children

With the school year now solidly underway and more people making their return to the workplace, the U.S. is once again facing a familiar wrinkle to dealing with the COVID-19 pandemic: the return of flu season.

Labcorp aims to tackle both infections with a single test following a new emergency authorization from the FDA for an at-home collection kit to gather samples from children as young as two years old.

The company said the combination test under its Pixel brand will be available at no upfront cost to people meeting certain clinical guidelines for screening, such as those who have been exposed to COVID-19 or currently have symptoms as well as those who have been directed to get a test by their healthcare provider.

“In time for flu season, the single test helps doctors and individuals make more informed treatment decisions given that symptoms of COVID-19 and flu are similar,” Labcorp’s chief medical officer and diagnostics president, Brian Caveney, M.D., said in a statement.

This can include fevers, runny noses and coughs. The test itself relies on a Roche cobas diagnostic for the coronavirus plus influenza A and B, while Labcorp’s at-home kit includes a short nasal swab designed for sweeping the lower nostril and a prepaid FedEx envelope for shipping the sample back to the lab. 

Labcorp estimates a turnaround time of 24 to 48 hours for results after the swab is delivered. To date, the company said it has performed more than 50 million PCR tests since the pandemic began spreading across the U.S. in March 2020 and that it can currently process up to 300,000 tests per day.

Labcorp’s at-home collection kits started hitting virtual and in-store shelves this past April, following the FDA’s initial emergency green lights allowing it to be self-performed and without a prescription.

https://www.fiercebiotech.com/medtech/fda-greenlights-combination-at-home-test-for-covid-and-influenza-children-as-flu-season.

Xenon finally finds a way forward with epilepsy win

 Seven years after floating Xenon could finally have found a winner. Highly encouraging data from the phase 2b X-Tole trial of XEN1101 sent shares in the company to a record high. The study tested the Kv7 potassium channel modulator in adults with focal epilepsy; XEN1101 significantly reduced seizure frequency versus placebo across three doses, and hit secondary measures. This was a highly refractory patient group that had failed a median of six previous anti-seizure medications; half remained on three background ASMs. On a call Xenon executives said it was highly unlikely to win approval on this trial alone, but hoped that regulators would accept X-Tole as one of two required studies. Safety also looked encouraging, with no suggestion that XEN1101 was worsening mood; many ASMs have a black box warning of suicidal ideation. Stifel analysts said the data beat expectations and looked in line with the recently approved Xcopri. To put a value on the opportunity, Angelini agreed to pay almost $1bn earlier this year for Arvelle, owner of Xcopri's European rights. Analysts expect Xcopri's sales in the US, where it is sold by SK Biopharmaceuticals, to reach $846m by 2026, according to Evaluate Pharma.

Source: Xenon investor presentation.

https://www.evaluate.com/vantage/articles/news/snippets/xenon-finally-finds-way-forward-epilepsy-win