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Wednesday, January 20, 2021

Oxford-AstraZeneca Covid Vax Helps U.K. Lead Race to Reach Nursing Homes

 The coronavirus has torn through nursing homes in the U.K., as it has in the U.S., taking tens of thousands of lives. Now, the U.K. hopes it is turning the tide, thanks to a homegrown vaccine that has yet to be authorized elsewhere in the West.

More than four million of the most at-risk people in the U.K., almost 8% of the adult population, have been vaccinated with at least one shot of vaccine.

Among them are more than half of the frailest group of all: the 300,000 elderly residents of nursing homes who can't travel to get a shot. The key to reaching them has been mobile vaccination teams armed with a shot developed by the University of Oxford and AstraZeneca PLC.

Together with a network of family doctors and vaccination hubs in sports centers, hotels and cathedrals, this shot has helped the country to stay on track toward a target of vaccinating its 15 million most vulnerable people by mid-February.

The government says the AstraZeneca vaccine, which has also been authorized in India, Morocco and some countries in Latin America, has been a game changer in reaching people tucked away in smaller nursing homes.

Doctors say that it is more efficient to deliver because it doesn't need diluting and that after the injection patients don't need monitoring for anaphylaxis. Both steps are time restraints when administering the other vaccine available in the U.K., one manufactured by Pfizer Inc. and BioNTech SE.

The AstraZeneca shot can be stored for six months at regular fridge temperatures of 2 to 8 degrees Celsius, meaning it can be moved several times and used in very small batches. The Pfizer shot, which has also been authorized in the U.S. and in Europe, is delivered in large batches and must be stored at minus-70. Once thawed it must be used in 3 1/2 days.

Helen Salisbury, a local doctor in Oxford, vaccinated some of her older homebound patients on Jan. 15 with the AstraZeneca vaccine. "It's much easier to carry around and we can take it from house to house," Dr. Salisbury said. "I went on my bike."

That versatility means supplies of the AstraZeneca shot are being prioritized for nursing homes, according to a letter sent to all family doctors in England on Jan. 13 that also offered them a cash incentive for giving first doses to residents.

Before the arrival of the AstraZeneca shot in early January, only larger nursing homes of more than 50 beds could be efficiently accessed with the Pfizer vaccine, according to the government's vaccine delivery plan, even after permission was granted to split the 975-dose boxes into smaller 75-dose trays. Now, smaller residential facilities, including those with fewer than 25 beds, are getting the vaccine, the plan says.

Speaking Monday, Scotland's Chief Medical Officer Gregor Smith pointed to studies showing that a life can be saved with as few as 20 vaccinations in nursing homes, compared with 600 vaccinations among over-70s living in the community. Giving priority to people in care homes at the front of the vaccination campaign, Dr. Smith said, "is time well spent."

Uddhav Bhatta, the manager of Langley Haven Dementia Care Home in Slough, west of London, had his first Pfizer shot in mid-December and his second last week. But residents had to wait until Jan. 14 for AstraZeneca's vaccine.

"It would have been difficult to come out with the Pfizer vaccine" to the nursing home, Mr. Bhatta said the doctor told him.

One thing now holding them back: a shortage of both vaccines, and here the AstraZeneca shot is at a disadvantage.

Unlike the new, gene-based technology used in the Pfizer vaccine and one from Moderna Inc., which is cleared for use in the U.K. but won't be supplied until the spring, the AstraZeneca shot relies on conventional vaccine production using a weakened form of a common-cold virus, known as an adenovirus. This makes it slower to grow than the mRNA vaccines, even if it is easier to administer.

Moderna's vaccine has less stringent shipping and storage requirements than Pfizer-BioNTech's, but they are still more restrictive than AstraZeneca's and the vaccine must be kept at minus-4 degrees Fahrenheit or refrigerated for up to 30 days once thawed.

AstraZeneca's shot has been available in the U.K. since Jan. 4, and the company said it had delivered 1.1 million doses to the country as of Jan. 13. The plan is to deliver two million doses a week in the near future and ship 100 million throughout the country by the end of this year.

The government says that it has the infrastructure and vaccinators it needs to administer such quantities and that the "rate-limiting factor is the supply of vaccine."

AstraZeneca says certain steps in the three-to-four month process of manufacturing the vaccine can't be accelerated. It takes between 58 to 60 days to grow the cells needed for the virus to replicate inside and then a further 28 days to prepare the vaccine via a process known as fill-and-finish before packaging and releasing in batches. Around 60 quality tests are performed during the process, and each batch is tested by the U.K. medicines regulator before being cleared for clinical use.

This is where the new vaccines based on mRNA technology, like Pfizer's and Moderna's, have an advantage. Their manufacturing process is a lot quicker. It takes about two hours to make the RNA. It must then be purified, formulated and encapsulated into lipid nanoparticles before being put into vials and tested.

"In total to make the RNA drug substance, the active ingredient, that would take around two days," said Zoltán Kis, a research associate at the Future Vaccine Manufacturing Hub at Imperial College London. Quality testing then takes about two weeks, he added.

On Monday, British Health Minister Matt Hancock said the government was over halfway toward its target of offering a first shot to all residents in its more than 10,000 nursing homes for older people in England by the end of this month.

In Scotland, more than 80% of people living in nursing homes and 55% of those caring for them have had a first dose of vaccine, according to First Minister Nicola Sturgeon.

Nursing homes aren't yet out of the woods. Covid-19 deaths among nursing-home residents in England began to rise again at the end of last year and continued to rise at the start of this one, after a period of relatively few fatalities throughout the summer and fall.

Five of Langley Haven's residents died of Covid-19 in April during the first wave of the pandemic. The home, which cares for 30 residents, didn't have another case until last week, when five residents and a member of staff tested positive for the virus, Mr. Bhatta said.

"It's a big relief [to have the vaccine] but we still don't know how infective" those who have had the shot are, he adds, "so we have to be careful."

Vaccine trials didn't determine whether immunizations against Covid-19 symptoms stopped patients from passing on the virus that causes the disease. Scientists are studying those vaccinated in recent weeks to determine whether the shots do have an impact on transmission.

Last week, Covid-19 broke out in the first nursing home in Scotland where residents were vaccinated with the Pfizer-BioNTech vaccine, in December.

"There's a myth out there that vaccination makes you Superman or Wonder Woman," said Donald Macaskill, chief executive of Scottish Care, an umbrella group representing nursing homes. "Our hope is that as time goes by and we get a population base that has been vaccinated, then these incidents will become fewer and fewer."

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-Oxford-AstraZeneca-s-Covid-19-Vaccine-Helps-U-K-Lead-Race-to-Reach-Nursing-Homes-32234913/

Merck KGaA, Glaxo suffer lung cancer drug setback

 

Merck KGaA's drug development programme has suffered a setback with the most important clinical trial of its cancer drug hopeful bintrafusp alfa stopped because the treatment does not appear to work.

The halt also puts a damper on the oncology ambitions of Britain's GlaxoSmithKline, which is co-developing the drug with Merck under a 2019 agreement that could have seen it pay up to 3.7 billion euros ($4.5 billion) to the German company.

In a statement on Wednesday, Merck KGaA said the late-stage trial dubbed INTR@PID Lung 037, testing the novel drug against U.S. namesake Merck & Co's bestseller Keytruda in newly diagnosed cases of a certain type of lung cancer, would be discontinued.

It said independent supervisors concluded the drug was unlikely to show the desired efficacy.

Merck KGaA's shares dropped as much as 7% but had pared losses to trade 3.3% lower at 1355 GMT.

Keytruda dominates a class of immunotherapies known as checkpoint inhibitors, and is expected to generate $17 billion in revenues this year.

Merck KGaA and Merck & Co Inc, known as MSD outside North America, share historic roots but have been under separate ownership since World War One.

The bintrafusp alfa drug is a so-called fusion protein designed to trigger both checkpoint inhibition and another immune response booster known as TGF-beta-inhibtion.

While several other experimental drugs are based on TGF-beta-inhibtion, the combination is a unique approach in the pharma industry.

https://www.marketscreener.com/quote/stock/GLAXOSMITHKLINE-PLC-9590199/news/GlaxoSmithKline-Merck-KGaA-GSK-suffer-lung-cancer-drug-setback-32237261/

UnitedHealth Tops Q4 Earnings Forecast, Confirms 2021 Guidance

 UnitedHealth Group Inc.  (UNH) - Get Report posted stronger-than-expected fourth quarter earnings Wednesday, and confirmed its 2021 profit forecast, as Optum continues to power the health care provider's top and bottom lines.

UnitedHealth said adjusted profits for the three months ending in December came in at $2.52 per share, down 35.4% from the same period last year but  11 cents ahead of the Street consensus forecast. Group revenues, UnitedHealth said, rose 7.55% to $60.5 billion, essentially in-line with analysts' estimates of a $65.1 billion tally.

UnitedHealth also reiterated its profit forecast for 2021, which it published in early December, and sees a range for adjusted earnings of between $17.75 and $18.25 per share, with revenues in the region of $277 billion to $280 billion, a 9% increase from the group's 2020 forecast. 

UnitedHealth said in December that the 2021 forecasts include a hit of $1.8 per share that reflects costs linked to "accommodate continuing COVID-19 effects, such as: treatment and testing costs; the residual impact of people deferring care in 2020; and unemployment and other economic-driven factors.

https://www.thestreet.com/investing/unitedhealth-tops-q4-profit-forecast-confirms-2021-guidance

Can Merck/Bayer Verquvo stand out in ever-more-competitive heart failure field?

 Bayer and partner Merck & Co. have carried a new heart failure drug across the FDA finish line, hoping to carve blockbuster share out of an ever-more-competitive field. As industry watchers see it, the two will have a hard time getting there in the face of stepped-up competition from Novartis and AstraZeneca.

The FDA Tuesday approved Verquvo, or vericiguat, to treat patients with chronic heart failure with reduced ejection fraction (HFrEF). The go-ahead is limited to a group of high-risk patients who’ve recently been hospitalized or received diuretics as outpatients for acute decompensated heart failure.

Now, Verquvo’s entering a market where Novartis’ fast-growing Entresto is establishing itself as the new standard of care and the SGLT2 class of diabetes drugs is trying to win a place with AstraZeneca’s recent landmark approval for Farxiga.

Bayer, the original developer of Verquvo, has pegged peak sales at €1 billion. The German company shares the drug’s responsibilities 50-50 with Merck through a deal signed in 2014. But analysts believe the drug has a smaller role to play as physicians will likely save it for last-line treatment in sicker patients.

Based on the approval—and a failed phase 2 Vitality trial in heart failure with preserved ejection fraction (HFpEF)—SVB Leerink analyst Daina Graybosch in a Wednesday note projected a “very slow sales ramp” for Verquvo, with 2021 U.S. sales to be in “low single-digit millions,” rising to merely $50 million in 2022 and 2023. Her U.S. peak sales estimate landed at $300 million, which is based on a 30% penetration in a subgroup of HFrEF patients that are not optimally managed on Entresto.

Merck views Verquvo’s patient selection criteria not as a “subpopulation,” Joerg Koglin, vice president of global clinical development at the company, said in an email interview. Instead, a worsening event could be a specific “clinical trigger” in a patient’s disease journey. “As such, we believe that Verquvo represents a meaningful addition to the treatment armamentarium for heart failure physicians,” he said.

Verquvo is an sGC stimulator, working on a pathway key in cardiovascular functions. Bayer markets the first sGC stimulator approved in the U.S., Adempas, in pulmonary arterial hypertension.


The drug proved its case in the phase 3 Victoria trial. Compared with placebo, it delivered a 10% relative risk reduction in composite cardiovascular-related death and heart failure hospitalization, according to data presented at the 2020 American College of Cardiology virtual meeting. Industry watchers have picked out some caveats in those data—as well as potential upsides—for Verquvo.

First, some industry opinion leaders saw the 10% improvement as “modest,” according to SVB Leerink analysts. While Victoria enrolled sicker patients than Entresto and Farxiga’s separate trials, “the physicians cautioned against assuming a role for [Verquvo] for severe patients as the benefit of other HF therapies in this population could be just as good or better,” the SVB Leerink team wrote in a July note.

Instead of relative risk reduction, Koglin pointed to the absolute risk reduction. “For patients, physicians and payers, the most relevant efficacy parameter is the absolute risk reduction translating into ‘how many patients do I have to treat with a new therapy to prevent one heart failure hospitalization or CV death,'” which is technically known as the number needed to treat, or NNT, Koglin said. On that marker, Verquvo compares well to other recent heart failure studies, he said.


Secondly, the drug’s beat on the trial’s primary endpoint was mainly driven by re-hospitalization improvement, while the cardiovascular death benefit wasn’t clear. Looking more closely, though, Graybosch noted that the trend appeared to lean more in Verquvo’s favor after two years. The divergence “suggests long-term, real-world outcome(s) could be better” for Verquvo, she said in a note last March.

One thing that could make Verquvo special is its potential to help patients already on Entresto. In the Victoria trial, patients were allowed background therapies, and 15% of them entered the trial while taking the Novartis drug. Koglin said Verquvo “illustrated the same benefit in patients on Entresto and patients without Entresto,” adding detailed data on this subgroup will be forthcoming.

Overall, Graybosch characterized physician sentiment toward Verquvo as being “pleased” to have an additional therapeutic option. To be “enthusiastic,” the doctors are banking on potential positive quality-of-life benefit and real-world registry data confirming the drug’s benefit in those treated with Entresto, she wrote in the March note.

https://www.fiercepharma.com/pharma/merck-bayer-win-fda-nod-for-verquvo-even-more-competitive-heart-failure-field

Pfizer-BioNTech Covid vax works just as well against variant first detected in UK

 The Covid-19 vaccine from Pfizer-BioNTech appears to work just as well against a fast-spreading variant of the coronavirus first identified in the United Kingdom as it does against earlier forms of the pathogen, the companies reported in a study Wednesday.

The paper from company scientists, which has not yet been peer-reviewed, is a welcome signal that existing vaccines don’t seem to be weakened by the variant in question, dubbed B.1.1.7. Already, scientists had tested the Pfizer vaccine against one of the key mutations in the variant and found the immunization’s neutralization power was not affected.

Scientists are also testing vaccines against other variants of concern, which contain different mutations that in lab experiments have shown they can, to some extent, help the virus evade existing antibodies that recognize and target the virus. These mutations appear in variants first seen in South Africa and Brazil, which also look to be more transmissible than earlier iterations of the SARS-CoV-2 virus. The variants in South Africa and Brazil have raised concerns that they can more easily reinfect people who have already recovered from Covid-19 and have antibodies against the virus, though more studies — including whether there’s some impact on how well vaccines work — are ongoing.

In the new study, researchers engineered what are called pseudoviruses (these are more practical to work with in lab experiments than actual live specimens of dangerous viruses like SARS-2) to have the full suite of mutations as B.1.1.7. They then tested blood taken from 16 people who had received the vaccine against the variant, and found it could neutralize the variant as well as it could an earlier form of the virus. “These data … make it unlikely that the B.1.1.7 lineage will escape” protection from the vaccine, the researchers wrote.

Experts say it’s possible some of the new variants may not respond as well to existing vaccines as other forms of the virus. But they stress that the vaccines generate incredibly robust immune responses, so they can withstand some drop in their potency without losing their ability to protect people against Covid-19.

“The efficacy of the vaccine is so good and so high that we have a little bit of a cushion,” Rochelle Walensky, the incoming director of the Centers for Disease Control and Prevention for the Biden administration, said Tuesday in an interview with the editor of JAMA.

Eventually, it’s expected the virus could pick up enough significant mutations that vaccine makers will need to update their immunizations, a process that experts say would likely take a matter of weeks to months, not years.

https://www.statnews.com/2021/01/20/pfizer-biontech-covid-19-vaccine-works-just-as-well-against-variant-first-detected-in-u-k-study-indicates/

Priority Review OKd for Bristol Opdivo Adjuvant Therapy for Esophageal, Gastroesophageal Cancer

 U.S. Food and Drug Administration assigned a target action date of May 20, 2021

Application based on Phase 3 CheckMate -577 trial, in which Opdivo doubled median disease-free survival versus placebo in patients with esophageal or gastroesophageal junction cancer following neoadjuvant chemoradiation therapy and surgery

Opdivo demonstrated a manageable safety profile consistent with prior studies

https://www.businesswire.com/news/home/20210120005097/en/U.S.-Food-and-Drug-Administration-Accepts-for-Priority-Review-Application-for-Opdivo%C2%AE-nivolumab-as-Adjuvant-Therapy-for-Patients-with-Resected-Esophageal-or-Gastroesophageal-Junction-Cancer

Gritstone, Genevant Sciences in License Agreement for COVID-19 Vaccine

 Gritstone Oncology, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company developing the next generation of cancer and infectious disease immunotherapies, and Genevant Sciences, a leading nucleic acid delivery company with world-class platforms and the industry’s most robust and expansive lipid nanoparticle (LNP) patent estate, today announced an agreement pursuant to which Gritstone has obtained a nonexclusive license to Genevant’s LNP technology to develop and commercialize self-amplifying RNA (SAM) vaccines against SARS-CoV-2, the virus that causes COVID-19. Genevant’s LNP platform is clinically validated and part of Gritstone’s SAM neoantigen-based cancer immunotherapy now in Phase 2 testing.

https://www.globenewswire.com/news-release/2021/01/20/2161371/0/en/Gritstone-and-Genevant-Sciences-Announce-License-Agreement-for-COVID-19-Vaccine.html