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Monday, October 4, 2021

AstraZeneca: FDA Granted Breakthrough Tag for Cancer Treatment Enhertu

 AstraZeneca PLC said Monday that the U.S. Food and Drug Administration granted its cancer treatment Enhertu a breakthrough-therapy designation for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer.

HER2 refers to a breast cancer that tests positive for a protein called human epidermal growth factor receptor 2.

The U.K. pharmaceutical company said that the FDA granted the designation based on the DESTINY-Breast03 Phase 3 trial, and that this is Enhertu's second BTD in breast cancer, bringing the total number to four.

The company said Enhertu's trial showed it reduced the risk of disease progression or death by 72% in patients with HER2-positive metastatic breast cancer.

The BTD designation is designed to accelerate the development and the regulatory review of potential new medicines that are intended to treat a serious condition, the company said.

Enhertu is a HER2-directed antibody drug conjugate that is being developed jointly by AstraZeneca and Daiichi Sankyo Co.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-Says-FDA-Granted-Breakthrough-Therapy-Designation-for-Cancer-Treatment-Enhertu-36591062/

J&J to seek U.S. FDA authorisation of booster shot this week

 Johnson & Johnson is planning to ask U.S. federal regulators this week to authorize a booster shot of its COVID-19 vaccine, the New York Times reported https://www.nytimes.com/live/2021/10/04/world/covid-delta-variant-vaccine#johnson-johnson-will-seek-fda-authorization-for-a-booster-shot on Monday, citing officials familiar with the company's plans.

https://www.marketscreener.com/news/latest/J-J-to-seek-U-S-FDA-authorisation-of-booster-shot-this-week-NYT--36592150/

COVID Prevention Tx Safe, Shows Efficacy in High-Risk Groups

 A monoclonal antibody cocktail designed for COVID-19 pre-exposure prophylaxis was safe, and appeared to be effective across populations at risk of severe COVID and who may have a subpar response to vaccination, a researcher said.

AZD7442 (tixagevimab/cilgavimab) met its primary endpoint, reducing the risk of symptomatic COVID-19 among high-risk populations by 77% (95% CI 46%-90%), though the absolute numbers were small (eight cases in the intervention group vs 17 in the placebo, HR 0.23, 95% CI 0.10-0.53), reported Myron Levin, MD, of the University of Colorado Denver School of Medicine in Aurora.

When stratifying by subgroups, such as older adults and those at high risk for severe COVID, there were numerically fewer cases in the intervention group versus placebo, but the numbers were small, and the confidence intervals were wide.

The treatment also appeared safe, with adverse events (AEs) balanced between groups, and no COVID-19 related deaths in the intervention group, Levin said at a late-breaking presentation at the virtual IDWeek.

Manufacturer AstraZeneca already released topline results of the PROVENT study in August, which showed that the treatment met the primary endpoint, but this presentation included data on subgroups, as well as safety data. It included a median 83 days of follow-up.

In August, FDA authorized an additional dose of mRNA vaccine for certain immunocompromised patients, such as solid organ transplant patients.

Levin noted the treatment would be targeted to individuals with "impaired immune responses and impaired immune function" who not only would be more likely to have severe COVID-19, but less likely to be protected against COVID-19.

"We know from ... vaccinology that prevention is always better than treatment if it's successful," he said.

Moreover, Levin pointed out that the treatment "successfully neutralized" the Delta variant.

The PROVENT trial was comprised of unvaccinated adults (ages 18 and up) at increased risk of inadequate response to vaccination or COVID-19 infection, who were randomized 2:1 to receive either the treatment or placebo. Overall, 3,460 adults received a single dose, including two intramuscular injections of AZD7442, and 1,737 adults received placebo.

Primary outcome was RT-PCR positive symptomatic illness, according to CDC criteria, which as Levin pointed out, "permits a very low bar for study endpoints to be observed," since it only requires one symptom.

About 1.4% of participants in the intervention group and 1.3% in the placebo group had at least one serious AE. There were four deaths each in the intervention and placebo groups, including from illicit drug overdose, renal failure, and myocardial infarction. The placebo group had two COVID-19 related deaths from acute respiratory distress syndrome.

Levin said the sample size for some groups was "limiting," but was consistent across subgroups. For example, adults, ages 60 and up, had three cases of COVID in the intervention group versus six in the placebo (RRR 75.1, 95% CI 0.5-93.8). There were eight cases in the intervention group and 11 in the placebo (RRR 63.6, 9.4-85.4) among adults at high risk for severe COVID.

He described how future research will try to find the "niche" of individuals where the preventive treatment would work best.

"Clearly there are people ... who do not respond" to vaccination, Levin said, and the treatment is "designed for people who are not going to respond to the vaccine or lose response early on."

However, AZD7442 is not meant as a substitute for vaccination, he added.

He added that while the data indicate the treatment was effective for at least 3 months, the data cutoff could underestimate long-term efficacy, as pharmacokinetic modeling predicts the treatment may provide protection for up to 12 months.

IDWeek session moderator Adarsh Bhimraj, MD, of the Cleveland Clinic, spoke about the importance of doing "quality randomized controlled trials" even "in the midst of a raging pandemic."

"So far we've been using COVID therapies and studying them as blunt instruments and not as precision missiles, and hopefully in the future we'll have better studies," he said.


Disclosures

IDWeek is the annual joint meeting of the Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, Pediatric Infectious Diseases Society, HIV Medicine Association, and Society of Infectious Diseases Pharmacists.

AZD7442 was developed in part with support from the U.S. government. This trial was partially supported by AstraZeneca.

Levin disclosed support from Johnson & Johnson, Novavax, Moderna, GlaxoSmithKline, Merck & Co, Pfizer, Dynavax , and Seqirus.

Sunday, October 3, 2021

New Covid vaccine will be needed next year: BioNTech CEO

 A new Covid vaccine is likely to be needed by next year to protect people from future mutations of the coronavirus, said the head of BioNTech SE, the German company that developed the first Covid vaccine. 

Ugur Sahin, co-founder and chief executive officer of BioNtech, has said that current variants of Covid, such as the delta strain, are not different enough to undermine current vaccinations. However, new strains will emerge that can evade booster shots and the body’s immune defenses, Sahin told Financial Times.

He said this year a different vaccine is completely unneeded, “but by mid-next year, it could be a different situation". This is a continuous evolution, and that evolution has just started," he said. 

BioNTech joined hands with US pharma giant Pfizer to develop its coronavirus vaccine. 

Last month, the companies submitted initial data to U.S. regulators about the use of the vaccine in children aged 5 to 11, one step closer to bringing shots to school-age kids. 

https://www.livemint.com/news/india/new-covid-vaccines-will-be-needed-next-year-predicts-biontech-ceo-11633262870318.html

Japan Government in Talks to Procure Merck's Potential Covid-19 Drug

 --The Japanese government is in talks to procure Merck & Co.'s potential Covid-19 drug as soon as the end of the year, Japanese business daily Nikkei reported Sunday without citing sources.

--If the drug is approved in the U.S. and an application is made in Japan, the country's health ministry would consider approving the drug through an expedited process, the Nikkei report said.

https://www.marketscreener.com/quote/stock/MERCK-CO-INC-13611/news/Japan-Government-in-Talks-to-Procure-Merck-s-Potential-Covid-19-Drug-Nikkei-Reports-36590265/

First Responders Aren't Prepared For Lithium Fires When Teslas Crash And Uncontrollably Burn

 With 40% of new cars predicted to be electric by 2030, Baltimore County's volunteer firefighter's association hopes Tesla can figure out how to stop making portable fireballs.

Investment bank UBS predicts by 2025, 20% of all new cars sold globally will be electric. Then by 2030, new sales will jump to 40%, and by 2040, every new car sold globally will be electric. The electric car adoption curve appears parabolic, and emergency responders need improved methods to safely and quickly extinguish electric vehicle fires as they're likely to become more frequent. 

Take, for example, a Tesla crash in Towson, Maryland, on Thursday evening. The vehicle immediately caught fire after it smashed into a median. The driver was unharmed, but the fire raged out of control after multiple fire stations didn't have the proper resources to extinguish the flames.

"The fire escalated to fully involved within about five minutes, officials said. Firefighters initially used portable extinguishers, but a foam unit from the fire department's hazmat unit was deployed, along with copious amounts of water, to cool the fire as it intensified due to damaged battery-powered cells that contain lithium, which ignites when exposed to oxygen," local news WBAL said. 

Traditional fire extinguishers, such as foam and water, are ineffective at immediately extinguishing lithium-metal fires. A class-D dry powder extinguisher is certified for use in lithium fires, though there was no mention if firefighters that night had that or a lithium fire blanket to isolate the fire. Instead, a large-capacity water tanker, hazmat unit, and a foam unit were called in and eventually extinguished the blaze two hours later. 

Commenting on the fire, one Twitter user said: "What is going to happen if the majority of cars are electric. Every accident/car fire can't require this level of Emergency Service assets." 

Sounding frustrated, the Baltimore County Volunteer Firefighters Association responded to the user and said: "Let's hope @elonmusk can work with the fire service and together we can develop a better response." 

Earlier this summer, 20 tons of water were used to extinguish a Tesla fire in Taiwan. For some context, it only takes 3 tons of water to put out a gasoline car fire. A Texas fire chief told The Independent that a Tesla fire needed 40 times more water to control the blaze in a separate incident.

The National Transportation Safety Board (NTSB) has encouraged electric car companies to educate and help emergency responders on techniques and new tools to put out lithium-ion battery fires. But in the Baltimore fire, the three firehouses appeared not to be well versed in controlling a lithium fire. 

Meanwhile, where's all that lithium going to come from, and how will environmentally conscious world leaders dispose of it?

https://www.zerohedge.com/markets/fire-crews-arent-prepared-lithium-fires-when-teslas-crash-and-uncontrollably-burn

Covid-19 charges at hospitals can vary by tens of thousands of dollars

 The cost of similar Covid-19 treatments can vary by tens of thousands of dollars a patient, even within the same hospital, according to a Wall Street Journal analysis of pricing data that indicates pandemic care hasn’t escaped the complex economics of the U.S. health system.

One kind of patient, with a type of severe respiratory condition that is common among those admitted with Covid-19, is an example of the wide range. The rates for these patients usually spanned from less than $11,000 to more than $43,000, the analysis found, but some prices could be far higher, depending on the severity of the case.

At NewYork-Presbyterian Weill Cornell Medical Center in New York, the cost for a severe-respiratory patient was around $55,182 if the person were insured by CVS Health Corp.’s CVS -0.93% Aetna, according to the hospital’s data. For UnitedHealth Group Inc.’s UNH 0.43% UnitedHealthcare, the hospital’s disclosed rate is $64,326, while the price listed in the hospital’s data for patients covered by Anthem Inc.’s ANTM 0.84% Empire Blue Cross Blue Shield was $94,357.

The range of prices shows how similar hospital services can generate widely disparate bills. Even during the pandemic, and within the same hospital, the prices often reflect the leverage that an insurer has to wrangle discounts, as well as the hospital’s market power to drive up its rates.

A spokeswoman for NewYork-Presbyterian said it negotiates each insurance contract individually and the cost to patients varies significantly depending on the care they receive, their coverage and their eligibility for financial assistance. A spokeswoman for Anthem said the insurer’s rate appeared higher because of how it was calculated and disclosed by the hospital, and it reflected that the hospital is treating sicker patients. Aetna said rates vary for a number of reasons, while UnitedHealth said the rates disclosed by hospitals don’t reflect the actual service costs.

Throughout much of the pandemic, insurers waived out-of-pocket charges for Covid-19 treatment, so the variable costs didn’t directly affect patients’ pocketbooks. Now, patients are increasingly facing charges such as deductibles or coinsurance, which can depend on rates that hospitals and insurers secretly negotiated, according to the Kaiser Family Foundation.

"Some have limited insurance and they are getting these crazy bills, and they’re saying, ‘I don’t know how I’m going to get through it,’" said Adria Goldman Gross, chief executive of MedWise Insurance Advocacy, a patient-advocacy firm in Monroe, N.Y.

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A federal fund that can pick up the cost of Covid-19 treatment is focused on the uninsured. As a result, many patients with private coverage may actually pay more out of their pockets than those with no health plan at all.

The pricing data became public this year under a new federal requirement. The Wall Street Journal analyzed this data for hundreds of hospitals, compiled by Turquoise Health Co., to understand what Covid-19 treatment costs. The analysis focused on private insurance, the kind offered by employers or purchased individually, not government-backed plans under Medicare or Medicaid.

The analysis included three types of hospital patients: those with serious respiratory illness who typically avoided treatment with ventilators; respiratory patients who needed ventilators for at least four days; and patients who had a life-threatening condition, known as sepsis, and may also have briefly needed a ventilator.

The Journal examined rates for billing codes for those conditions, which were the codes most frequently associated with privately insured Covid-19 patients in claims analyzed by Milliman Inc., an actuarial firm.

The analysis looked at rates at more than 600 hospitals. In describing price ranges, the Journal has excluded the most extreme figures unless they were directly verified with the hospital and insurer involved, to ensure accuracy.

Covid-19 treatment doesn’t have its own designated billing code. Since the codes can also be used for patients with other conditions, the prices listed in the data likely wouldn’t reflect any extra bump in payment insurers give hospitals specifically for Covid-19 patients.

At the top end of the ranges were some substantially higher rates that hospitals said corresponded to the sickest, most difficult cases.

Patients admitted for Covid-19 treatment may require stays in the intensive-care unit and ventilators to help with breathing. If their insurer has stopped blocking out-of-pocket charges for virus treatment, patients could face bills in the thousands of dollars tied to the prices that the companies have negotiated.

"You will have no control over what services are provided to you and you will have virtually no control over the cost," said Susan Null, principal at Systemedic Inc., a medical billing and patient advocacy firm in New City, N.Y.

For the billing code that reflects inpatient care requiring more than four days on a ventilator, the prices at the middle of the range were around $90,000, the analysis found. The rates in some cases, however, went well above $200,000.

Kettering Health’s hospital in Hamilton, Ohio, listed a top rate of $115,604 for Humana Inc. for the billing code for severe respiratory conditions that don’t typically require ventilators. It was among the highest prices in the Journal’s analysis for that code.

It represented the rate for one particular patient who "reflects a one-off, high-intensity case, creating an outlier," said Michael Mewhirter, chief financial officer for Kettering Health, which includes nine hospitals. The hospital’s contracted rate for that code with Humana is $22,000, he said.

The price is roughly the median in the Journal’s analysis for that code.

A Humana spokesman said the higher price "does not align with Humana’s contracted rate for this type of admission" for an average patient.

At MemorialCare Orange Coast Medical Center in Fountain Valley, Calif., the listed Cigna Corp. price of $424,773 for the ventilator billing code represented one Cigna patient who was in the hospital for 27 days. The typical Cigna rate for cases with that same billing code that don’t require such a high amount of care is around $147,000, said John Cascell, a senior vice president at MemorialCare. The figure is above the 70th percentile in the Journal’s analysis for that code.

A Cigna spokeswoman said, "Isolated examples do not provide meaningful insights" when evaluating Covid-19 costs.


Another factor in the rates: whether an insurer can bring a large volume of patients to the hospital. Hospitals tend to give better prices to those that can.

For the sepsis patient billing code commonly associated with Covid-19, a MultiPlan Corp. price posted by George Washington University Hospital in Washington, D.C., was $76,795—more than twice the next-highest rate, which was listed for a separate MultiPlan brand, according to the analysis.

MultiPlan offers networks of doctors and hospitals that insurers and others can use. Its rates applied to just one patient at George Washington University Hospital since 2018 who was treated for sepsis conditions commonly associated with Covid-19, compared with major insurance companies that bring more business, said Jane Crawford, spokeswoman for Universal Health Services Inc., which owns the D.C. hospital. "Those organizations bringing the fewest patients receive the smallest discounts," Ms. Crawford said.

The published prices don’t accurately reflect MultiPlan’s pricing structure, said Pamela Walker, a MultiPlan spokeswoman. MultiPlan sets prices for each good or service, and doesn’t bundle them into a single rate comparable to the hospital’s published price, she said. MultiPlan declined to give an estimate for a comparable price, saying there were too few patients with data to get an accurate figure.

https://www.foxbusiness.com/economy/covid-19-charges-at-hospitals-can-vary-by-tens-of-thousands-of-dollars-a-wsj-analysis-finds