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Thursday, July 8, 2021

Covid's delta variant is highly contagious. Will vaccines work against it?

 The delta variant now accounts for half of the Covid-19 cases in many areas of the U.S., President Joe Biden said Tuesday, urging unvaccinated Americans to get the Covid-19 shots as the U.S. faces a dramatic rise in the "hypertransmissible" variant of the coronavirus. His plea included reassurances about the strength of the Covid-19 vaccines available in the U.S.


"Fully vaccinated Americans have a high degree of protection, including against this delta variant," Biden said at a news briefing, pointing out that virtually all Covid-19 hospitalizations and deaths in recent months have been among the unvaccinated.

Former Defense Department immunologist John Grabenstein, a former executive director of medical affairs for vaccines at Merck, said the delta variant is "more contagious, more spreadable."

"That makes it dangerous, because it's more likely to find the people who are not vaccinated," he said.

The variant has risen as the U.S. vaccination rate has stalled, and recent reports about a drop in vaccine effectiveness have triggered worries even among people who are fully vaccinated.

How effective are the vaccines against the delta variant?

There are two ways to answer this question. One is by analyzing blood samples from people who have been fully vaccinated.

Scientists can take Covid-19 antibodies found in the blood and test them against variants. Several such independent lab studies (here and here, for example) found that the vaccines in use do, in fact, protect against the delta variant of SARS-CoV-2, as well as reduce hospitalizations. The studies are considered preliminary and haven't been peer-reviewed.

They also provide a limited picture of all the ways the immune system works against Covid-19, because they measure only antibody response. Certain cellular responses also play key roles. T cells, for example, help by killing infected cells and harnessing the power of other immune cells in the fight against viruses. Lab studies don't usually measure T-cell response.

The second — and maybe more important — way to determine vaccine effectiveness is by simply observing what's happening in the real world in real time.

"It's very hard to translate laboratory data into 'what's going to happen if I'm vaccinated and someone sneezes on me and spreads delta all over my face?'" said Dr. David Wohl, a professor of medicine in the infectious diseases division at the University of North Carolina at Chapel Hill, who runs UNC's vaccine clinics.

That's why it's important for scientists to look to places like the United Kingdom, where the delta variant accounts for nearly 100 percent of current Covid-19 cases. Despite having higher vaccination rates than the U.S. — 68 percent in the U.K. have had at least one dose, compared to just under 55 percent in the U.S. — cases are rising in the U.K.

"The only real difference between us and them is delta," Wohl said. "I'm really worried that what's going on in the U.K. is precisely what's going to happen here."

"If you're waiting for some magical moment" to get vaccinated, he said, "this is it."

While Covid-19-related hospitalizations in the U.K. have risen slightly in recent weeks, they are nowhere near what they were at the peak of the pandemic in January.

Experts say reports from Israel about a drop in vaccine effectiveness against the delta variant are intriguing because the country vaccinated a majority of its population before the U.S. did, and it now faces a surge in variant-related cases. A recent study from Israel found that the Pfizer vaccine was just 64 percent effective in preventing symptomatic illness in fully vaccinated people.

At the same time, the report found that the vaccine was 93 percent effective at preventing hospitalizations and serious illness — a significant benefit, experts say.

"Maybe the vaccine isn't preventing the really mild cases. That's OK," Grabenstein said. "It is preventing the really severe infections, the things that we fear the most."


Experts have been skeptical about the report from Israel's Health Ministry, mainly because the study's authors neglected to provide many details about how they did their research and who participated.

"Assuming these data are correct, this is telling us that it's even more urgent than ever for people to get vaccinated," said Dr. Jesse Goodman, a professor of medicine and infectious diseases at Georgetown University Medical Center, who is a former chief scientist with the Food and Drug Administration.

Pfizer didn't respond directly to the Israeli study, but it pointed to lab data about its vaccine response to the delta variant published in early June, suggesting that it had neutralized the variant, although with less strength relative to previous strains. And a recent report from Public Health England found two doses of the Pfizer vaccine to be 96 percent effective against hospitalization for the delta variant.

Grabenstein said that even if the data ultimately check out, he doesn't mind, "because I'm most reassured by the 93 percent against the really severe forms of the infection."

Do vaccinated people spread the virus?

Vaccines aren't meant to prevent infection. Their strength is in preventing the infection from making people sick and landing them in the hospital.

Most breakthrough infections among fully vaccinated people tend to be mild or to occur without symptoms. What remains unknown is whether an unsuspecting carrier can spread the virus to vulnerable people, such as the unvaccinated, children under age 12 or those with compromised immune systems.

Goodman said infected people who have been fully vaccinated probably have less virus in their system and therefore are probably less likely to transmit it to others. The time person is contagious is also probably shorter with vaccination, he said.

Should vaccinated people wear masks indoors?

It's unlikely that the Centers for Disease Control and Prevention will reinstate recommendations to wear masks. But because of the unknown level of transmissibility of delta among fully vaccinated people, experts said in interviews that they continue to wear masks indoors when they are around people they don't know, such as in grocery stores or movie theaters or on public transportation.

"I have never changed my behavior, and I'm fully vaccinated," Wohl said. "If I'm indoors, around other people who could be unvaccinated, I wear a mask.

"With Delta spreading, that's the way we should be."

https://www.nbcnews.com/health/health-news/covid-s-delta-variant-highly-contagious-will-vaccines-work-against-n1273114

Despite Mixed Data, Sinovac's COVID-19 Vaccine is Second Most Used Globally

 While several countries are relying on Sinovac Biotech’s coronavirus disease 2019 (COVID-19) vaccine to end the pandemic once and for all, concerns regarding the shot’s efficacy continue to shroud the vaccine, which is currently the second most used COVID-19 vaccine product across the globe.

Sinovac’s CoronaVac was the first COVID-19 vaccine approved in China for emergency use back in June 2020. Countries relying on the company’s vaccine typically have little access to the mRNA vaccines from Moderna and Pfizer-BioNTech. To date, approximately 380 million doses of this vaccine have been sent across the world.

And although the Beijing-based biotech’s vaccine has demonstrated success in clinical trials, efficacy rates have ranged from 50% to as high as 90% across clinical trials conducted in Turkey, Brazil and Indonesia. Sinovac has since kept mum on these data and hasn’t provided explanations or further details on why protection rates vary from study to study.

In an exclusive interview with Bloomberg, the company’s chief executive officer Yin Weidong indicated the priority has been to approve the vaccine by regulators versus addressing or explaining negative coverage in the media. He told the outlet that little else mattered as long as people were getting vaccinated against the novel coronavirus.

But Sinovac’s lack of media presence and inability to control data access from its trial partners may have tarnished the shot’s reputation, more so than it likely deserves. Real-world evidence suggests the company’s vaccine does indeed possess high levels of efficacy against COVID-19.

In an Indonesia trial, for instance, approximately 94% of 130,000 healthcare workers who were fully inoculated with Sinovac’s vaccine were reportedly protected from symptomatic infection with SARS-CoV-2. Another 96% of healthcare workers in this study were protected from COVID-19-related hospitalization and 98% were protected from death.

Despite these high rates of protection, the CEO of the company was reportedly unaware of this study and the corresponding data.

This lack of awareness didn’t stop the company from submitting other clinical and non-clinical research data to the World Health Organization, which on Wednesday authorized Sinovac’s two-dose CoronaVac COVID-19 vaccine for emergency use in people 18 years and older.

The European Medicine Agency has also started a rolling review of the company’s vaccine, which is the first step toward receiving EU approval for use.

Back in April, Sinovac completed the third phase of a vaccine bulk production manufacturing facility, resulting in the per-year production capacity exceeding 2 billion doses. To date, the total supply of CoronaVac has reached over 600 million doses, while incomplete data show more than 430 million doses have been administered across the globe.

In addition to pending approvals and authorizations, the United Arab Emirates recently reported it will start offering a third booster shot for people treated with the Sinovac vaccine. The country said the booster shot was to be used to counteract the less-than-anticipated antibody generation in some people who received the two-dose inoculation.

https://www.biospace.com/article/-acceptance-of-sinovac-s-covid-19-vaccine-grows-across-the-globe-despite-hurdles-and-disparate-efficacy-data/

Akero NASH Drug Reduced Liver Fat to Normal Levels, Reversed Fibrosis: Study

 Akero Therapeutics, Inc. (Nasdaq: AKRO), a cardio-metabolic biotechnology company developing transformational treatments for non-alcoholic steatohepatitis (NASH), today announced that full results of the main portion of its Phase 2a BALANCED trial in biopsy-confirmed NASH patients with F1-F3 fibrosis have been published in Nature Medicine.

The manuscript, available at this link, provides a comprehensive analysis showing that pre-cirrhotic NASH patients treated for 16 weeks with Akero’s investigational drug, efruxifermin (EFX), an FGF21 analog, achieved substantial reductions in liver fat, associated with decreases in markers of liver injury and inflammation, and reversal of fibrosis after only 16 weeks treatment. Numerous endpoints are reported for the first time in Nature Medicine.

“This disclosure of EFX data in Nature Medicine marks the first published clinical evidence of fibrosis regression with an FGF21 analog and what we believe are the largest reductions in liver fat publicly reported to date across all NASH investigational drug classes,” said Kitty Yale, chief development officer of Akero. “We’re pleased to contribute to the field of NASH clinical research with publication of these data. We extend gratitude to the trial participants who made this study possible.”

NASH is a serious, potentially life-threatening condition that is a leading cause of liver failure and liver transplantation globally. An estimated 17.3 million Americans had NASH in 2016, a number that is expected to increase to 27.0 million by 2030. There are currently no approved therapies for NASH. Weight loss of 10 percent or more has been shown to reverse NASH by restoring normal levels of liver fat and reducing insulin resistance. Unfortunately, achieving this degree of weight loss through lifestyle change is very challenging.

Moderna's first seasonal flu vaccine slides into clinic as pharma giants crowd into mRNA

 Now that mRNA technology has the FDA’s backing, Moderna has moved on to its next act, a vaccine to improve upon the annual flu shot, as plenty of Big Pharma giants breathe down the biotech's neck.

The Cambridge, Massachusetts-based company, made famous by the success of its COVID-19 vaccine, has dosed the first patient in a phase 1/2 clinical trial for a new seasonal influenza vaccine.

Moderna is developing mRNA-1010 to protect against common flu strains as recommended by the World Health Organization. The company is hoping to improve on traditional flu shots which are typically about 40% to 60% effective. Most of these shots are developed using eggs, which Moderna said can cause unintended changes to the vaccine virus. The strains to be used in the vaccines are also decided six to nine months ahead of time, meaning a lot of guesswork as to which strain might be dominant during flu season.

The clinical trial for mRNA-1010 will ultimately enroll 180 healthy adults to test the vaccine’s safety, how patients react and how well it works.


Moderna enters the clinic surrounded by giants on all sides—from Sanofi to Pfizer to GlaxoSmithKline—who believe with the success of the COVID-19 vaccines, that mRNA is a new frontier for vaccine development.

Working with Translate Bio, Sanofi claimed to have commenced the first human trial of a seasonal mRNA flu vaccine candidate in June, beating Moderna and other rivals to the clinic.

The technology works by teaching a patient’s cells to make a protein that can trigger an immune response in the body and spur the creation of antibodies and therefore protection against a virus. While the authorization of the COVID-19 vaccines marked the first time mRNA had been cleared by regulators, the technology has been studied for decades.

Moderna has used mRNA vaccines in trials before, though aimed at specific flu strains: Back in 2019, it dropped early data from several phase 1 tests showing its mRNA vaccines against H10N8 and H7N9 influenza viruses "were well-tolerated and elicited robust immune responses."

This latest attempt is aiming wider using a seasonal approach that targets multiple strains, including influenza A H1N1, H3N2 and influenza B Yamagata and Victoria.

Pfizer, which developed an mRNA COVID-19 vaccine that beat Moderna to the U.S. market last year, sees mRNA becoming a large part of the pharmaceutical giant’s future. The company thinks the 95% efficacy seen with the COVID-19 vaccine could translate into a major improvement for the yearly flu shot.

Sanofi last month announced plans to throw $476 million a year to a dedicated vaccines mRNA Center of Excellence in an effort to become a leader in developing mRNA vaccines against a wide range of infectious diseases.


And then there’s GSK, which is working with CureVac on five clinical-phase mRNA-based vaccines through a $294 million deal.

In addition to the flu, Moderna is developing vaccines for HIV, respiratory syncytial virus and others.

The biotech is also looking at combining some vaccines into one single shot. Other companies have beaten them to the punch there, too, such as Novavax, which is already testing a COVID-flu vaccine in animals.

“Respiratory combination vaccines are an important pillar of our overall mRNA vaccine strategy,” said Moderna CEO Stéphane Bancel in a statement. “Our vision is to develop an mRNA combination vaccine so that people can get one shot each fall for high efficacy protection against the most problematic respiratory viruses.”

https://www.fiercebiotech.com/biotech/moderna-s-first-flu-vaccine-candidate-slides-into-clinic-as-pharma-giants-crowd-into-mrna

Cel-Sci CEO tries to spin cancer trial failure into a win

 Cel-Sci CEO Geert Kersten begged investors in 2018 to hold on until phase 3 data could prove the struggling biotech’s cancer drug worked. Fast forward to 2021: The results are in, and they are unlikely to inspire the rally needed to save the company.

The biotech's stock price plummeted 45%, losing more than $11 per share and dropping to $13.69 after the news was issued June 28. The tumble has continued, with the stock sitting at about $8.38 apiece Wednesday.

Kersten has turned to his keyboard once again in an effort to spin the results for Multikine into a win.

“Some false assertions and misrepresentations have been made and published by parties who either did not understand the protocol and statistical analysis or had ulterior motives pertaining to our stock price,” Kersten wrote in a letter to stockholders published Wednesday.


Here’s what the results said: Multikine failed to improve overall survival when added to standard of care treatment in the overall population tested in the phase 3 head and neck cancer study. Cel-Sci wanted to see at least a 10-percentage point improvement on this metric when Multikine was added to standard of care, comprising surgery, radiotherapy and chemotherapy. This was the main goal of the trial, meaning the test was unsuccessful.

But Cel-Sci plans to file the drug for FDA approval anyway, focusing on a narrow subset of patients who did not receive the chemotherapy part of their treatment. The study showed a 14-percentage point improvement in overall survival in this group.

This is where Kersten believes the “confusion” arises from. By confusion, he means an investor revolt that has turned into at least one class action lawsuit from shareholders alleging the company’s officers and/or directors engaged in securities fraud or unlawful business practices.

According to Kersten, the data spurred accusations that the company had engaged in “data mining” and “p-value hacking.” Cel-Sci was accused of sitting on the data for a year before landing on the subgroup analysis as a way to move the therapy forward anyway. Questions arose as to whether Cel-Sci could even use the subgroup data for a filing because they were not prespecified in the study’s initial endpoints.

Kersten cited an unnamed statistician to support his case that no mining or hacking had occurred. He claimed the subgroup analysis was prespecified, meaning the company can use these data to file for FDA approval. He also said the p-value data were “in fact very strong.”


The p-value measures the probability that the effect observed in the trial is a result of the experimental treatment and not merely chance. The lower the number, the better it is for the study. Cel-Sci reported that the overall survival results for Multikine plus standard of care without chemotherapy showed a p-value of 0.0236.

Kersten complained that short sellers had targeted the company before the results were issued and therefore had an interest in seeing the shares plummet.

“But now, the data clearly shows that Multikine extends life in 40% of newly diagnosed advanced primary head and neck cancer patients,” Kersten wrote. He said that if Multikine is cleared by the FDA, tens of thousands of patients with head and neck cancer may live longer. “What kind of person continues to sell short and attack a company that can make this kind of difference in the lives of cancer patients?”

Back in 2018, Kersten’s letter pointed to this data release as a “key inflection point” that could right the ship after several rocky years. He promised the biotech had a "promising future" ahead. 

In reality, Cel-Sci had just made a pitch to the New York Stock Exchange to try to hang on to its listing, stockholders had an equity deficit and the company reported net losses on the five prior fiscal years. The company was also emerging victorious from a lawsuit with a contract research organization that was involved in a phase 3 study for head and neck cancer that ran from 2011 to 2013. The legal action had shaken the confidence of investment funds and analysts, but Kersten said at the time that the win should put the hesitation to bed.

 

Despite all of those events, Kersten believed the company was way undervalued at the time.

In a December 2020 (PDF) 10-K filing, Cel-Sci calculated its net losses at $384 million since inception, with $30.2 million clocked for fiscal year 2020. The company has not commercialized any products and receives revenue only through the sale of securities. This is expected to continue "for the foreseeable future."

"Multikine is the only product candidate in late-stage clinical development, and Cel-Sci’s business currently depends heavily on its successful development, regulatory approval and commercialization," the filing stated.

The FDA has not cleared a new drug for this type of advanced head and neck cancer in decades. Cel-Sci will now take the data to the FDA for a meeting ahead of a regulatory filing for patients to receive Multikine followed by surgery and radiation—but not chemotherapy.

Cel-Sci clearly hopes the subgroup will push Multikine—and the company—to a new inflection point.

https://www.fiercebiotech.com/biotech/data-mining-and-p-value-hacking-cel-sci-ceo-tries-to-spin-cancer-trial-failure-into-a-win

AstraZeneca-Amgen drug gets FDA's speedy review for asthma

 Drugmaker AstraZeneca AZN.L said on Thursday its experimental drug tezepelumab was granted a speedy review by the U.S. Food and Drug Administration for potential approval as a treatment for asthma, with action expected in the first quarter next year.

The medicine, developed along with U.S-based Amgen AMGN.O, showed in trials it can reduce asthma attacks in patients with severe and uncontrolled forms of the respiratory condition, with promise for wider use against different triggers.

https://www.nasdaq.com/articles/astrazeneca-amgen-drug-gets-fdas-speedy-review-for-asthma-2021-07-08

Biogen, FDA walk back controversial Aduhelm label after weeks of fierce criticism

 Following weeks of fiery criticism for its wide-labeled approval for Biogen’s Aduhelm for anyone with Alzheimer’s disease, the FDA is now narrowing the recommended window of patients to only those with milder forms of the memory-robbing disease. 

Biogen on Thursday said the FDA approved an updated label for Aduhelm, also known as aducanumab, that recommends the amyloid-beta targeting antibody for people with mild cognitive impairment or mild dementia, aligned with those included in Biogen’s late-stage trials. 

The FDA warns that there is “no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.” 


Biogen requested the update based on “ongoing conversations with prescribing physicians, FDA and patient advocates,” research head Alfred Sandrock, Jr., M.D., Ph.D., said in a statement. The goal is to “further clarify the patient population that was studied across the three Aduhelm clinical trials that supported approval,” Sandrock added.

The slimmed approval follows the FDA’s decision to award Aduhelm an “almost shockingly broad” label, as some analysts put it, in early June, essentially giving Biogen free reign to the estimated 6 million Alzheimer’s patients living in the U.S. 

Intense pushback followed as market watchers pointed out that the drug could overwhelm payer budgets, particularly Medicare, which covers most Alzheimer's patients in the U.S.

Although Biogen’s label update comes just over a month since Aduhelm’s initial approval, it follows a string of stinging rebukes, including from high-ranking lawmakers, against the Cambridge-based drugmaker. 

On Capitol Hill, Biogen has faced criticism over its $56,000 per year list price for Aduhelm, the only approved drug intended to slow the progression of the disease. In some estimations, given the FDA’s expansive go-ahead, Aduhelm could eventually balloon Medicare’s spending above the cost of all current Part B drugs. 


That’s all for a drug that has shown murky clinical benefits, at best, critics argue. Both Biogen and the FDA are now the subjects of a Congressional probe, spearheaded by the House Committee on Oversight and Reform, over the company’s pricing tactics, as well as the FDA’s approval process. 

As more details surrounding Aduhelm’s approval come to light, prominent Democratic lawmakers have targeted the FDA’s dealings with the drugmaker initiated well before the treatment was cleared in June. In a letter to the HHS on Tuesday, Rep. Katie Porter, D-California, charged Biogen with “undue influence” over the FDA’s review process.

https://www.fiercepharma.com/pharma/facing-pushback-biogen-and-fda-agree-to-narrow-aduhelm-s-broad-label