Target $50
Thursday, July 29, 2021
Antibody treatment eyed following swarm of breakthrough COVID-19 infections
While authorized vaccines have proven safe and effective in holding the line against COVID-19, they are not 100% effective. Reports of uncommon breakthrough cases among fully vaccinated Americans, coupled with the delta variant tearing through the country, threaten to undermine the fiercely fought wins against the pandemic.
For the fully vaccinated who do test positive, if you are at high risk for severe infection, health experts are now turning to Food and Drug Administration authorized, virus-fighting monoclonal antibodies in some cases. They are saying it's safe and beneficial for those who have been vaccinated, but get infected with COVID-19 nonetheless.
"Receiving antibody treatments in a timely manner could be the difference of ending up in the hospital or getting over COVID (quickly)," Dr. Shmuel Shoham, infectious disease physician at Johns Hopkins University School of Medicine, told ABC News.
Monoclonal antibodies are synthetic versions of the body's natural line of defense against severe infection, now deployed for after the virus has broken past the vaccine's barrier of protection. The therapy is meant for COVID patients early on in their infection and who are at high risk of getting even sicker to help keep them out of the hospital. This risk group includes people 65 and older, who have diabetes, high blood pressure, cardiac disease, obesity, asthma or who are immunocompromised.
It can be administered through an intravenous infusion, or a subcutaneous injection, which is less time-consuming and labor-intensive, and more practical in an outbreak situation.
The therapies still in use across the U.S., like Regeneron's antibody cocktail, has shown to hold up against the variants of concern, including delta.
It's a new use for a therapy whose authorization predates that of the vaccines.
"The trick is to proverbially cut the virus off at the pass," Dr. William Schaffner, professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center, told ABC News. "An ounce of prevention is worth a pound of cure."
Though a fraction of breakthrough cases have symptoms, the few that do may need backup to fight off the infection, experts say.
"There are exceptions. Everyone has seen a handful of patients who are vaccinated, you get very, very sick. Those are by and large, people with many risk factors, and perhaps people were vaccinated longer ago, with people in whom we don't expect the vaccine to work as well," Dr. Andrew Pavia, Infectious Diseases Society of America fellow, NIH COVID treatment guidelines panel member and chief of pediatric infectious diseases at the University of Utah School of Medicine said.
Clinical trials for monoclonal antibody therapies were conducted prior to vaccines' authorization, before shots started going into arms and far before breakthrough infections were a part of daily discussion. But the Centers for Disease Control and Prevention specifies that for vaccinated people who have subsequently contracted COVID, a vaccine should not preclude seeking further treatment.
"Prior receipt of a COVID-19 vaccine should not affect treatment decisions (including use of monoclonal antibodies… or timing of such treatments," the CDC said.
The chances of an allergic or adverse reaction is low, experts said. Regeneron's product targets the virus, not a protein produced by the body, a company spokesperson said -- so, it likely wouldn't trigger a haywire immune response with an antibody "overdose" from both the vaccine and the monoclonal therapy. And clinical trial data has shown authorized monoclonal antibody therapies can sharply reduce hospitalizations and deaths by as much as 70%.
A Regeneron spokesperson said as long as a patient has tested positive for COVID and meets the other criteria to receive the treatment, they can receive the therapy.
"We are not screening those patients out. If they have been vaccinated and come in testing positive and are at high risk for a more severe infection we are giving them monoclonals," Schaffner said. "I think that was decided pretty quickly."
It's a question of targeting the appropriate group of infected patients, experts said and it's not for anyone who has symptoms after testing positive. Doctors prescribe the therapy for patients with specific risk factors that make them unlikely candidates for fighting off the virus on their own. With your antibodies already being made to combat coronavirus, experts said another helping won't do as much good.
But Shoham calls it a "missed opportunity" for patients eligible to receive it -- who don't.
"If they had gotten a monoclonal antibody, their chance for hospitalization would have been significantly reduced," Shoham said.
"The vaccines are so good, that most people who have one or two risk factors that are vaccinated are less likely to become infected, and if they are -- the vast majority have done very well," Pavia said. "What we're trying to do is identify that small sliver of people with breakthrough infection that may get quite sick."
The antibody cocktail medications work best if it is delivered within days of a positive test or onset of symptoms. So, doctors recommend acting quickly after getting a positive test to seek treatment, if the high-risk criteria fit -- whether you have been vaccinated or not.
"This is a targeted treatment that is not for everyone -- it's not 'spaghetti at the wall' for when vaccines don't work," Schaffner said. "But this is good news on the therapeutic side."
https://abcnews.go.com/Health/antibody-cocktail-answer-uncommon-breakthrough-covid-cases-put/story
With Aduhelm, history can repeat itself by following cancer’s success
The Food and Drug Administration’s approval of Biogen’s Alzheimer’s drug Aduhelm has stirred intense controversy, with pundits launching attacks on multiple fronts. Professors focus on population outcomes rather than individual treatment responses; politicians worry about drug pricing rather than disease cost; critics pounce on the FDA’s narrowing of the drug’s label to reflect its clinical trial — all casting doubt on the drug’s effectiveness and value.
What’s been lost in the flurry is an understanding of how progress against complex diseases advances — and the historic importance of Aduhelm as a first step in that process.
Alzheimer’s robs people of memory, cognition, and the dignity of being human. It is a public health crisis that will eventually bankrupt every health care system challenged with financing institutionalized care for the coming wave of dementia patients. There is no cure and no standard therapy. The wasteland of research failures causes many investigators to shy from committing careers to Alzheimer’s, while the biopharmaceutical industry avoids the risk of futile investments of billions of dollars.
This year, for the first time since Alzheimer’s was first described in 1906, the FDA granted what’s called accelerated approval for a drug with substantial evidence of affecting the underlying disease mechanism, though its effects on symptoms remains to be elucidated.
Fifty years ago, when the National Cancer Act was passed, cancer posed much the same threat as Alzheimer’s disease poses today: no cure, only rudimentary understanding of the disease, and an enormous emotional and financial toll on families and society. Yet many forms of cancer are now amenable to cures or long periods of remission and control.
This progress did not take place in one giant leap.
In the earliest days of cancer chemotherapy, a modest response rate of 20% to 30% was celebrated as a victory, especially compared to zero. Those responses mattered because they exposed tumors’ vulnerabilities and offered hope for those who responded to treatment and their loved ones.
As a cancer physician and former director of the National Cancer Institute, I believe the burden should be on critics to explain why we should not view biological responses to Aduhelm in people with Alzheimer’s the same way and follow the same road map to greater success.
Early, tentative responses to new therapies mobilized the cancer community to a sustained effort at building on incremental progress. With patience, persistence, and the heroic participation of cancer patients who braved potential side effects, researchers and clinicians made astounding gains.
In my own experience as a urologic oncologist, the results in widespread metastatic testicular cancer have been stunning. Once a virtual death sentence with no curative treatments, patients now experience an almost 100% survival rate utilizing a combination of chemotherapy agents.
This history of progress in the fight against cancer shows that the FDA was right to approve Aduhelm — not as a silver bullet but as a first, essential step in climbing a mountain to success for people with Alzheimer’s disease and their families.
Obscured by the current angst is that Aduhelm demonstrated a profound effect on amyloid plaques in patients’ brains. A peer-reviewed study offered evidence why Aduhelm may work when previous anti-amyloid therapies failed: Aduhelm appears to interrupt the cascade of damage from toxic molecules becoming plaque — “uniquely” among the antibodies studied, according to the authors.
Researchers will eventually discern whether amyloid plaque is a cause of Alzheimer’s disease or an effect of it. But reduction of plaque is an essential observation — just as in a cancer trial where survival is the meaningful endpoint but tumor response is the critical observation because it shows researchers they are on a path that matters.
The FDA has launched this journey for Alzheimer’s with the accelerated approval of Aduhelm. In fact, the agency has already taken the next step by granting Eli Lilly’s Alzheimer’s treatment, donanemab, breakthrough designation, which is intended for serious or life-threatening conditions in which preliminary clinical evidence supports a potential significant improvement over existing therapies.
The process of incremental innovation will accelerate as evidence of Aduhelm’s biologic effects accumulates. Clinicians who choose to use this drug have a responsibility to collect data and share information with colleagues, the drug sponsor, and the FDA. Oncology was fortunate to have an infrastructure in place, utilizing the NCI Designated Cancer Centers and Cooperative Clinical Trial Groups launched by the National Cancer Act. Today that infrastructure can be virtual. Modern tools of data acquisition, aggregation, and analysis leave no excuse for not assembling a registry of patients and insights into their response to therapy. Biogen should create such a registry to follow every patient who gets Aduhelm. That could significantly accelerate progress against Alzheimer’s disease.
Aduhelm is not a silver bullet in the battle against Alzheimer’s, and the hand-wringing critics are wrong to hold it to that standard. The more productive route is to recognize the drug as a first treatment that can galvanize the scientific/medical community, industry, and patient advocates to begin the hard, step-by-step process that leads to better treatments and hopefully, one day, a cure. That’s the future we all wish for Alzheimer’s and all neurodegenerative diseases. That’s the effort we owe to desperate patients living in fear they will not recognize or remember the names of their loved ones.
Andrew C. von Eschenbach is an oncologist, president of Samaritan Health Initiatives, former director of the National Cancer Institute, former commissioner of the Food and Drug Administration, and a member of the board of Wren Therapeutics. He reports having no financial relationships with Biogen.
https://www.statnews.com/2021/07/29/aduhelm-history-repeat-itself-following-cancer-successes/
What's the Evidence Guiding CDC's Latest Mask Policy?
Throughout the pandemic, we learned a lot about which drugs help and which don't. Steroids are of indisputable benefit when given to hospitalized patients who require oxygen or mechanical ventilation. Hydroxychloroquine does not work in a similar situation. Many things we thought might help, were found to offer no net benefit. We are much better off from having this knowledge.
Randomized trials were the scientific tool that allowed us to separate drugs that save lives from those that have no effect or even contribute to iatrogenic injury. Randomizing patients was the secret sauce to improving the care of people diagnosed with COVID-19, and I suspect future scientists will look back with admiration at the pandemic heroes: the trialists of RECOVERY and SOLIDARITY and other major randomized efforts.
When it comes to non-pharmacologic interventions such as mandatory business closures, mask mandates, and countless other interventions, the shocking conclusion of the last 18 months is this: We have learned next to nothing.
Yet, here we are again with CDC changing its mind on masking, but what new evidence is guiding the policy?
While CDC said vaccinated people with breakthrough infections from the Delta variant carry viral loads similar to the unvaccinated, they haven't yet shared any data on this, and this also doesn't negate the need for sufficient research into how and when mask mandates are effective. And no, I am not here to say that masking can't be an effective public health intervention. It may be, and people should mask-up when their local leaders tell them to. Instead, I am here to call attention to the need for evidence-driven policy.
Anyone who considers themselves a scientist should be embarrassed by our collective failure to generate knowledge, and this failure is once again looming large. The CDC is again recommending vaccinated people to wear cloth masks in indoor public spaces, at least in locations where COVID is surging. The CDC director calls this "following the science," but it is not. It is following the TV pundits.
Many studies have documented the flow of particles in and around masks, and countless studies have examined the differences between locations that implemented mask mandates and locations that did not. While this information is interesting, it is often conflicting, and worse, does not offer a sufficient basis for public health recommendations. Mechanistic studies are incapable of anticipating and tallying the effects that emerge when real people are asked to do real things in the real world.
Comparing places that implemented restrictions to those that did not is a fool's errand. The confounding variables abound: political valence, pre-intervention trends, other behavioral changes, and a host of other differences that are not easily adjusted for.
When it comes to drugs, for example, we would never accept this type of evidence. Knowing how hydroxychloroquine works in cells, and then comparing hospitals that used it versus those that did not would lead to confusion and ignorance. There are too many other factors. Only several well-done randomized trials adjudicate the uncertainty.
With the Delta variant and vaccination at play, the ignorance is even greater. Not only do we know very little if, and when, and under what circumstances mask mandates offer benefits, we know absolutely nothing about how this might operate in the face of a variant after individuals have been vaccinated. At what case rates are mask mandates most effective? Do they work only if you encourage surgical masks or is a cloth mask enough? Does this hold for vaccinated individuals in the setting of the Delta variant?
The CDC's guidance applies only to substantial and high transmission counties (50 daily cases or higher per 100,000 people), but again, there is no science that shows mandates work in these settings but not others. It is also a confusing and constantly changing metric to try to keep track of.
The CDC cannot "follow the science" because there is no relevant science. The proposition is at best science-y; a best guess based on political pressure, pundit anxiety, and mechanistic understanding.
The Second Order Effects
It is bad enough we have learned nothing about when and if mask mandates offer net gains, but this is compounded by the potential for second order effects.
If you start making vaccinated people mask again, will that be a disincentive for the "vaccine curious" to vaccinate? After all, they are already hesitant -- could they take from the guidance the tacit message that the vaccine is not that protective after all? P.S. -- The vaccine is that protective, and it retains amazing efficacy against Delta!
Will reinstating mandates be met by the same level of compliance as before? Will it lead to protests which have rocked other major global cities?
Worst of all is the likely scenario where the places with the political will to reinstitute mandates are probably liberal urban areas where vaccination rates are the highest and SARS-CoV-2 rates the lowest. Places that will be allergic to mask mandates -- southern, rural areas -- might be places where vaccination rates are the lowest and SARS-CoV-2 rates the highest. Ironically, the CDC's guidance might result in two different scenarios: excessive mask use where it won't help and inadequate mask use in places where it might help.
Let's also consider whether re-instituting masking will have even broader implications. Will it hurt the political fortunes of parties thought to support continued restrictions? Might the political ramifications have an impact on human health -- for example, through differences in funding for social programs?
The list of potential unintended effects goes on and on. Sadly, we know nothing here.
Science on Life Support
In a recent piece on public health, Monica Gandhi, MD, MPH, Stefan Baral, MD, MPH, and I argue that "in the beginning precaution is fine, but eventually public health must be driven by data." The amazing thing about COVID-19 is there are so many places where we know so much more than before, such as how to care for the hospitalized COVID-19 patient. But the tragedy is all the places where we know nothing more than when the pandemic began. Case in point: If and under what circumstances policy mandates help.
COVID-19 cases, which are rising now, will eventually fall, as seen in the U.K.. This is the inevitable dynamic of pandemic illness. One year from now, we still won't know if the CDC's action helped, hurt, or was merely coincidental.
When the history books are written about the use of non-pharmacologic measures during this pandemic, we will look as pre-historic and barbaric and tribal as our ancestors during the plagues of the middle ages. What the books won't capture is how, in the moment, our experts were simply so sure of themselves.
Vinay Prasad, MD, MPH, is a hematologist-oncologist and associate professor of medicine at the University of California San Francisco, and author of Malignant: How Bad Policy and Bad Evidence Harm People With Cancer.
https://www.medpagetoday.com/opinion/vinay-prasad/93803
COVID recovery drives U.S. credit rating upgrades to record high
The strong economic recovery in the United States has led to a record number of corporate credit rating upgrades this year, figures from S&P Global showed on Thursday.
The combination of vaccine rollouts, reopening the economy and ultra-low borrowing costs has boosted firms’ finances and made debt piles more manageable.
S&P said it had made a record 121 upgrades during the second quarter and 220 since the start of the year although that was still well below the 715 downgrades during the first half of last year as the pandemic spread.
Most of the upgrades in recent months have been of lower-rated firms with 58% of all upgrades of issuers rated ‘B’ and lower. They have also been led by several of the sectors hardest hit by the pandemic, and about half were of issuers that had been downgraded since the start of 2020.
The proportion of firms at risk of downgrades also fell by eight percentage points to 19%, and is now below its long-term average of 22%.
“This steady decline points to a further decrease in downgrade potential and indicates the number of quarterly downgrades should continue to fall,” S&P said.
The surge in oil and gas prices over the last 12 months mean the sector’s negative rating bias has fallen 39 percentage points this year, the most of any U.S. sector, although it remains fractionally above the long term average.
The retail and restaurant sector’s negative bias has fallen 32 percentage points this year, the second most among all sectors, while the media and entertainment sector’s 33% negative bias is the highest despite a 20 percentage points drop.
“We expect the recovery of pre-2020 credit metrics to be uneven, with the hardest-hit industries of out-of-home entertainment and hotels not expected to recover before 2023 and even later for the cruise industry,” S&P said.
AstraZeneca still eyes US vaccine filing despite another delay
- AstraZeneca confirmed on Thursday plans to seek a standard approval of its coronavirus vaccine Vaxzevria in the U.S., and not an emergency use authorization — a speedier path to market — as originally intended.
- AstraZeneca reported positive results from a Phase 3 trial in the U.S. in March and executives later said the company would seek an emergency clearance "in the coming weeks." But the timing for that application has slipped due to requests from U.S. regulators for more real-world data. The company now plans to file for full approval before the end of 2021, according to an earnings release.
- Despite its problems getting to market in the U.S., Vaxzevria is approved in more than 50 countries and is a key contributor to the international vaccine alliance COVAX, which is helping to secure shots for nations that can't afford them. The vaccine generated $894 million in sales for AstraZeneca in the second quarter, more than tripling its total from the first three months of the year.
Nonetheless, the company's admission is the latest chapter in what's become a long-running saga. Once a frontrunner in the U.S. and a recipient of one of the largest supply contracts for the Operation Warp Speed coronavirus vaccine initiative, AstraZeneca's progress has slowed due to a lengthy trial halt and multiple setbacks abroad, among them a link between its vaccine and a very rare side effect that temporarily stymied the shot's rollout in several European countries.
The company also got into an unusual public spat with a trial monitoring board in the U.S. over the results from its Phase 3 trial.
U.S. regulators, in the meantime, authorized vaccines from Pfizer, Moderna and Johnson & Johnson. The federal government has since stockpiled enough doses of each of them to cover the population, rendering AstraZeneca's shot an afterthought in the nation's immunization campaign.
And yet, through it all AstraZeneca's shot has still proven strongly protective against severe disease from COVID-19, a benefit that's held up both in clinical testing and beyond. Most recently, a preprint of a U.K. study showed the shot offered 92% protection against the worst outcomes from the fast-spreading delta variant.
The company still intends to push forward in the U.S., both with its original shot as well as a new shot tailored to a particularly evasive variant known as beta. That shot is currently in Phase 2/3 testing, with results expected by the end of the year, the company disclosed Wednesday.
But AstraZeneca's plans as a vaccine developer beyond that are unclear. In an interview with Reuters on Wednesday, Ruud Dobber, the executive vice president of AstraZeneca's biopharmaceuticals business division, said the company is "exploring different options" for the vaccine business and could come to a decision on its future by the end of the year. Prior to the pandemic, AstraZeneca had never developed or sold a vaccine, and Vaxzevria was licensed from the University of Oxford, not created in-house.
Pressed about the report on an earnings call, AstraZeneca CEO Pascal Soriot argued Dobber "may have been misquoted."
"We of course are going to look forward, but we haven't got any specific timeline for this," Soriot said. "We've been so busy working on delivering the orders we've got and working on the new variant options ... that our priority hasn't been to look at what we're going to do going forward."
Vaxzevria has been one of AstraZeneca's top-selling products in 2021, so far generating about $1.2 billion in sales. That figure is still well behind the likes of Pfizer and Moderna, which have projected more than $33 billion and $19 billion, respectively, in full-year sales of their vaccines.
AstraZeneca, however, is the only one of the three to vow not to profit from vaccine sales during the pandemic.
https://www.biopharmadive.com/news/astrazeneca-coronavirus-vaccine-us-filing-plans/604139/
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