Could an Antibody Drug Help You Shed Pounds? | Health News

By Amy Norton HealthDay Reporter

(HealthDay)

MONDAY, Nov. 2, 2020 (HealthDay News) — An experimental antibody drug that targets one of the body’s key metabolism regulators may help obese people lose weight — at least briefly.

That’s one finding from an early study that tested the injection drug, which mimics the effects of a natural hormone called fibroblast growth factor 21 (FGF21). In the body, FGF21 helps govern metabolism, calorie-burning and food intake.

Researchers found that a single injection spurred “metabolic improvements” in overweight and obese adults that lasted up to two months. On average, people started eating fewer calories after a week, and saw their “good” HDL cholesterol increase while their levels of “bad” LDL cholesterol, insulin and triglycerides all fell.

Beyond that, their food preferences started to shift away from sweets, and they managed to drop a couple pounds — albeit temporarily.

Experts called the findings “interesting,” but stressed the work is very preliminary.

“The purpose of this study was really to determine dose and to get an idea of proof of concept,” said Dr. Donna Ryan, a professor emerita at Pennington Biomedical Research Center in Baton Rouge, La. She was not involved in the study.

It would take much more research to prove the antibody is safe and effective, Ryan said. And that, she added, would be a “long, difficult and expensive proposition.”

She pointed to the bigger picture, saying there is “excitement” in the field of obesity drug development: Researchers are studying how various “molecules” in the body regulate metabolism, and trying to turn those molecules into medication. The injection drug Saxenda, approved in the United States in 2014, is an example, Ryan said.

The new research is of a piece with that, she said.

The findings were published Nov. 2 in the Proceedings of the National Academy of Sciences.

FGF21 is a hormone that helps control metabolism by stimulating certain receptors in fat tissue, the liver, the pancreas and the central nervous system. Past research has suggested that people who carry certain variants in the FGF21 gene tend to have a sweet tooth and a preference for carbohydrates.

In addition, people with obesity, type 2 diabetes or non-alcoholic fatty liver disease appear to have high levels of FGF21 in their blood.

That suggests they may have grown resistant to the hormone — similar to how people become resistant to insulin, said senior study author Dr. Puneet Arora.

Scientists have tried giving modified versions of FGF21 to benefit metabolism. But the protein is cleared from the body too quickly to be useful, explained Arora, who was with biotech company Genentech at the time of the study.

So, Arora and his colleagues there developed a lab-engineered antibody that essentially mimics the hormone.

As an initial test, they recruited 60 overweight and obese adults, then randomly assigned them to have a single injection of the antibody or a placebo. For about a week, the participants stayed at the research center, following a controlled diet. And by the end

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TFF Pharmaceuticals, Inc. and Augmenta Bioworks, Inc. Enter Into a Worldwide Joint Development Agreement for COVID-19 Monoclonal Antibody Therapies

Companies to collaborate in first-of-its-kind uses of Thin Film Freezing technology applied to monoclonal antibodies

TFF Pharmaceuticals, Inc. (NASDAQ: TFFP), a clinical-stage biopharmaceutical company, and Augmenta Bioworks, Inc., a biotechnology company enabling breakthroughs in medicine through immune profiling, today jointly announce that both companies have entered into a worldwide Joint Development and Collaboration Agreement to develop novel commercial products incorporating Augmenta’s human-derived monoclonal antibodies (mAbs) for potential COVID-19 therapeutics.

Under the terms of the Agreement, both companies will collaborate in a Joint Development Project to develop one or more commercial therapeutics based on, derived from, and/or incorporating Augmenta’s human monoclonal antibodies to potentially treat patients with COVID-19. These products will be developed utilizing TFF Pharmaceuticals’ Thin-Film Freezing technology to manufacture dry powder formulations of these specific mAbs for inhalation delivery directly to the lungs of patients. The Agreement also includes the development of formulations suitable for parenteral administration, where the Thin Film Freezing dry powder formulations can be reconstituted, potentially mitigating the impacts of cold-chain storage and handling. TFF Pharmaceuticals will also have the option to develop two additional Augmenta mAbs for indications other than COVID-19.

Augmenta Bioworks and TFF Pharmaceuticals will allocate patent license rights to their respective technologies to allow each company to jointly commercialize the products developed under the Joint Development Project. The companies have agreed to a 50-50 split of all costs and expenses to further the Joint Development Project and both companies have agreed to the same 50-50 split of all revenues, cash payments and/or future cash payments related to the sale and/or license of the products resulting from the Joint Development Project to a third party.

“This important agreement represents the culmination of many months of work by our scientific team, as we work towards the development of a never-before-achieved formulation of monoclonal antibodies into a dry powder therapeutic,” said Glenn Mattes, CEO, of TFF Pharmaceuticals, Inc. “It is a testament to the remarkable flexibility and capability of our Thin Film Freezing platform and we are eager to develop these potentially breakthrough mAb therapies internally, along with our other programs in Invasive Pulmonary Aspergillosis, solid organ transplant anti-rejection, and botanicals.”

“Confirmed discovery of novel anti-SARS-Cov-2 antibodies in 8 days was an achievement made possible by years of technology development, and a clear indication of the power and potential of our platform,” said Christopher Emig, Ph.D., CEO and Co-Founder of Augmenta Bioworks, Inc. “We are excited to enter this partnership to bring our COVID-19 treatment into clinical development, and are looking forward to the world’s first effective, affordable and scalable antibody therapeutic to mitigate the devastating effects of this disease.”

“We believe the interest in monoclonal-antibody therapeutics for the treatment of COVID-19 is extremely high, with the promise that they will harness the immune system’s natural response to viral invaders,” said Robert O. Williams III, Ph.D., Division Head of the University of Texas at Austin’s Division of Molecular Pharmaceutics and Drug Delivery and inventor of TFF Pharmaceuticals’ Thin Film Freezing technology.

“The challenge

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Two COVID-19 Outpatient Antibody Drugs Show Encouraging Results

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.

Two COVID-19 antibody treatments, one developed by Regeneron and the other by Eli Lilly, show promise in the outpatient setting in results released on Wednesday.

Regeneron, in a randomized, double-blind trial, is assessing the effect of adding its investigational antibody cocktail REGN-COV2 to usual standard of care in comparison with adding placebo to standard of care. A descriptive analysis from the first 275 patients was previously reported. The data described Wednesday, which involve an additional 524 patients, show that the trial met all of the first nine endpoints.

Regeneron announced prospective results from its phase 2/3 trial showing REGN-COV2 significantly reduced viral load and patient medical visits, which included hospitalizations, visits to an emergency department, visits for urgent care, and/or physician office/telemedicine visits.

Interest in the cocktail spiked after President Donald Trump extolled its benefits after it was used in his own COVID-19 treatment earlier this month.

Trump received the highest dose of the drug, 8 g, but, according to a Regeneron news release announcing the latest findings, “results showed no significant difference in virologic or clinical efficacy between the REGN-COV2 high dose (8 grams) and low dose (2.4 grams).”

The company described further results of the industry-funded study in the release: “On the primary endpoint, the average daily change in viral load through day 7 (mean time-weighted average change from baseline) in patients with high viral load (defined as greater than107 copies/mL) was a 0.68 log10 copies/mL greater reduction with REGN-COV2 compared to placebo (combined dose groups; p<0.0001). There was a 1.08 log greater reduction with REGN-COV2 treatment by day 5, which corresponds to REGN-COV2 patients having, on average, a greater than 10-fold reduction in viral load, compared to placebo.”

The treatment appears to be most effective in patients most at risk, whether because of high viral load, ineffective baseline antibody immune response, or preexisting conditions, according to the researchers.

According to the press release, these results have not been peer reviewed but have been submitted to the US Food and Drug Administration, which is reviewing a potential emergency use authorization for the treatment in high-risk adults with mild to moderate COVID-19.

Operation Warp Speed, the Trump administration’s treatment and vaccine program, contracted in July with Regeneron for up to 300,000 doses of its antibody cocktail.

Lilly Treatment Shows Drop in Hospitalizations, Symptoms

Another treatment, also given in the outpatient setting, shows promise as well.

Patients recently diagnosed with mild to moderate COVID-19 who received Eli Lilly’s antibody treatment LY-CoV555 had fewer hospitalizations and symptoms compared with a group that received placebo, an interim analysis of a phase 2 trial indicates.

Peter Chen, MD, with the Department of Medicine, Women’s Guild Lung Institute at Cedars-Sinai Medical Center, Los Angeles, California, and colleagues found that the most profound effects were in the high-risk groups.

The interim findings of the BLAZE-1 study, which was funded by Eli Lilly, were published online October 28 in The

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Antibody drug tested in Cook County may be helpful to some COVID-19 patients, results show

A new antibody-based drug shows promise in treating outpatients who have mild to severe COVID-19, according to initial results of research conducted in part at Cook County Health and Northwestern University.

Patients given the drug were hospitalized or visited the emergency room less often than those given a placebo, Cook County Health officials said. The patients receiving the drug also showed improvement within two to six days, a shorter disease course that is not only good for patients but also may reduce the amount of time a person is infectious, helping protect other people.

The drug, manufactured by Eli Lilly and AbCellera Biologics Inc., was tested on 452 outpatients at 24 medical institutions across the country, including Cook County’s vast public health system and the Northwestern University Feinberg School of Medicine. Most of the 14 patients who took part at Cook County Health were Latino or Black, populations that have been hit especially hard by the disease.

The results of the continuing study, which is being run by Eli Lilly, were published Wednesday by the New England Journal of Medicine.

The drug, administered through a one-time infusion, includes the replicated antibodies of one of the first patients in the United States to survive COVID-19. It’s classified as a monoclonal antibody treatment, the same type of medication given to President Donald Trump after he was diagnosed with the disease and which he described as “a cure.”

The drug in the Eli Lilly trial was formulated using a single antibody. The drug Trump received was made by Regeneron and involves two antibodies.

Dr. Gregory Huhn, an infectious disease expert who led the arm of the Eli Lilly research conducted at Cook County Health, made it clear that the drug is a treatment, not a cure.

“Our hope has been that the antibody drug will reduce COVID symptoms quickly after diagnosis and help to eradicate the virus more quickly,” Huhn said. “While a vaccine is still necessary, this drug therapy has the potential to prevent bad clinical outcomes and complications of COVID-19.”

Scientists have surmised that monoclonal antibodies would be more effective earlier in the course of the disease, and that so far appears to be the case. Another recently released study found the Eli Lilly drug had no benefit for patients sick enough to be hospitalized — results that brought the research to a halt. Most of those patients also were treated with the antiviral drug remdesivir.

“There’s a more compelling argument to administer antibodies early on, before our own bodies generate their own immune response,” Huhn said.

The results released Wednesday found that 1.6% of outpatients given the Eli Lilly drug needed to be hospitalized or visit an emergency room, compared with 6.3% of patients who received a placebo. The drug worked by reducing the amount of virus in people’s bodies, the study determined.

The study’s findings also indicate better outcomes among high-risk patients — defined as patients 65 or older or morbidly obese patients who were at least

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Trump administration agrees to purchase $375 million of Lilly coronavirus antibody drug

The Trump administration will pay Eli Lilly $375 million to supply 300,000 doses of its experimental antibody drug to treat COVID-19, the Department of Health and Human Services said Wednesday.

If the Food and Drug Administration authorizes use of the drug, the federal government will allocate the doses to state and territorial health departments which, in turn, will determine which health care facilities receive the drug for use in outpatient care.

Eli Lilly said it anticipates only high-risk patients will be indicated to receive the drug until more studies are completed and more supply is available.

The initial agreement is for delivery over the course of two months following authorization, with the option to purchase up to 650,000 additional doses through the end of June 2021 for up to an additional $812.5 million. 

The government-purchased doses would become available to Americans at no cost, although health care professionals could charge for administering the medicine.

Eli Lilly’s CEO, David Ricks, said the company is allocating the drugs to the countries that need them most and will commit only to a few months of supply at a time to any given country in order to match demand with the limited supply.

“Unfortunately, the U.S. now leads the world in both COVID-19 cases and deaths. As a result, a top priority is helping reduce disease burden in the U.S.,” Ricks said. 

The rolling seven-day average of daily cases in the U.S. topped 70,000, according to COVID Tracking Project data. With that many cases a day, the projected supply of the monoclonal antibodies would not be nearly sufficient to meet demand.

Eli Lilly said it anticipates manufacturing up to 1 million doses of its drug by the end of 2020, with 100,000 doses ready to ship within days of authorization.

The agreement with Eli Lilly is part of the administration’s Operation Warp Speed, the initiative created by the administration to fund the quick development and distribution of a COVID-19 vaccine.

Ricks said Eli Lilly is pricing the drug at $1,250 per vial in wealthy countries, with a tiered system based on the country’s ability to pay. One vial represents the full course of treatment.

Ricks said the company expects to make a profit and is pricing the drug “above our marginal cost to produce the medicine in developed markets,” meaning it expects “to produce a modest financial return for our investors by the end of 2021.”

The announcement of the agreement comes a day after Eli Lilly said the drug had no clinical benefit for helping hospitalized patients. The company said it is confident the drug is helpful to those earlier in the course of a COVID-19 infection.

Antibody drugs are experimental, and while doctors think they are promising as a potential treatment of COVID-19 and could be a bridge to a vaccine, clinical studies are still ongoing.

But President TrumpDonald John TrumpGiuliani goes off on Fox Business host after she compares him to Christopher Steele Trump looks to shore up support in

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U.S. signs deal with Lilly for supply of potential COVID-19 antibody drug

FILE PHOTO: Eli Lilly logo is shown on one of the company’s offices in San Diego, California, U.S., September 17, 2020. REUTERS/Mike Blake

(Reuters) – The U.S. Government has awarded an initial $375 million contract to drugmaker Eli Lilly and Co LLY.N to secure 300,000 doses of its potential experimental COVID-19 antibody treatment, a drug that has been touted by U.S. President Donald Trump.

Lilly will start delivering the treatment within two months of receiving an emergency use authorization from the U.S. health regulator, the company said.

The U.S. government also has the option to purchase up to an additional 650,000 vials for $812.5 million, the U.S. Department of Health and Human Services said in a statement.

While vaccines are seen critical to ending the pandemic, governments are increasingly looking at effective treatment options to slow the spread of the disease and kick-start economic activity.

The company submitted a request to the U.S. Food and Drug Administration earlier this month for emergency use authorization of the drug to treat mild to moderate COVID-19 patients.

The U.S. government has committed that patients will have no out-of-pocket costs for the medicine, although healthcare facilities may charge a fee for the product’s administration, Lilly said.

The antibody therapy is similar to a drug from Regeneron Pharmaceuticals REGN.O that was given to Trump during his bout with COVID-19.

The treatments belong to a class of drugs called monoclonal antibodies that are manufactured copies of antibodies created by the body to fight against an infection. Lilly’s antibody was identified from a blood sample taken from one of the first U.S. patients who recovered from COVID-19.

Reporting by Manas Mishra in Bengaluru; Editing by Saumyadeb Chakrabarty

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Lilly Stops Antibody Trial in Hospitalized COVID-19 Patients

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.

Eli Lilly announced it will halt its ACTIV-3 trial evaluating the antibody bamlanivimab in combination with remdesivir for people hospitalized with COVID-19, after new evidence regarding efficacy emerged.

The new data from the National Institutes of Health suggest that the experimental neutralizing antibody therapy does not offer significant clinical benefit for people with more advanced COVID-19 illness, according to a company statement.

Eli Lilly also announced it plans to continue its other trials evaluating the antibody, including those assessing a potential role in treating people in the earlier stages of COVID-19.

“While there was insufficient evidence that bamlanivimab improved clinical outcomes when added to other treatments in hospitalized patients with COVID-19, we remain confident based on data from Lilly’s BLAZE-1 study that bamlanivimab monotherapy may prevent progression of disease for those earlier in the course of COVID-19,” the statement reads.

The ACTIV-3 trial was paused on October 13 after a data and safety monitoring board cited safety concerns.

The most recent data update that triggered an end to the trial did not reveal any significant differences in safety, though.  

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and rheumatology. Follow Damian on Twitter:  @MedReporter.

For more news, follow Medscape on Facebook, Twitter, Instagram, and YouTube.

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Where Do I Go to Get My Covid Antibody Cocktail?

Scientists work with a bioreactor at a Regeneron Pharmaceuticals facility in New York, Oct. 2.



Photo:

Regeneron/Associated Press

Covid researchers are racing the clock. They’ve made enormous progress on therapies and vaccines, but they aren’t far enough along to arrest the current surge of Covid infections as winter approaches. One of the biggest challenges is making sure the new treatments reach the patients who need them most.

The most immediate opportunity comes from antibody drugs that can be used both as treatment and prophylaxis. President Trump and former New Jersey Gov. Chris Christie both recovered after they received antibody combinations when their symptoms were worsening. These medications are likely to be most effective when used before or soon after symptoms begin.

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The Food and Drug Administration is reviewing evidence for the emergency authorization of these drugs, aiming to get them to Covid patients before they need to be hospitalized. We recently wrote on these pages about some important steps to ensure an adequate supply. Available medicine will need to be used wisely on the patients who need it most.

There are also practical challenges of administering these medicines intravenously and under medical supervision. Sending Covid patients to infusion clinics is a bad option, since those facilities are full of cancer patients and others with suppressed immune systems who may be at serious risk if infected.

The federal government is working on a system to control distribution, essentially sending limited supplies to states in proportion to their expected eligible patients. Governors would allocate the drugs to hospitals, as happened with the antiviral drug remdesivir.

This will require collaboration from states and hospitals in setting up special administration sites. Such sites might include emergency departments. But when Covid strikes a metropolitan area, stressed emergency wards may not have the space. Moreover, ideally the antibody drug would be given to patients who aren’t yet very sick. Healthy patients are often reluctant to take infused drugs, which feel riskier than swallowing pills. Having to spend three hours at a hospital will make that perception worse.

A more flexible approach would include modular sites or conversions of other hospital spaces. Health-care providers have also substantially expanded home infusion capabilities during the pandemic. It might be possible to treat some Covid patients at home, staffed by medical professionals trained to handle the small risk of allergic reactions. The FDA would need to authorize the drugs for delivery in home settings. The risk of managing reactions to the drug must be weighed against the risks that patients will avoid the hospital and forgo the therapy altogether.

A related issue is payment. Even if the antibody drug is free for patients, providers need reimbursement for the substantial costs of administering the

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UCSF study in Bay Area neighborhood reveals 10% of those tested have COVID-19 antibody

UC San Francisco released a preliminary analysis Thursday of data from a coronavirus testing effort in Oakland’s Fruitvale neighborhood and it confirmed what other similar studies have found: The novel coronavirus disproportionately affects the Latino community.

UCSF, in conjunction with local community groups, offered free, voluntary COVID-19 testing Sept. 26 and 27 in Fruitvale, a corner of Alameda County that has had the highest rates of COVID. Fruitvale is 50% Latino and home to one of the largest Mayan-speaking populations outside of Mexico, according to UCSF. Many residents live in multigenerational households.

Nearly 2,000 people were tested for either active infection or antibodies.


A total of 1,099 people were tested for active infection with nose swabs, and of those, 4% tested positive (29 adults and 10 children).

Of those with coronavirus, 95% were Latino, though they represented 62% of individuals tested, according to UCSF.

Of the 859 individuals (803 adults and 56 children) who were tested for the COVID-19 antibody, 10% were positive, suggesting past infection. Latino individuals had a positivity rate of 12% and those of Mayan heritage 27%.

At a Friday morning press conference, Oakland Mayor Libby Schaaf called the study results “disturbing but not unexpected data” revealing the health disparities in the city. “And let’s be honest, in the world,” she added.

“Our data further identifies the Mam speaking, Mayan population as particularly high risk within the Latino community,” Dr. Alicia Fernandez, a professor of medicine and director of the UCSF Latinx Center of Excellence, said in a statement. “More testing and targeted public health messaging are needed, as are efforts to make essential work safer.”

Researchers also gathered data to examine the overall impact of the pandemic and found 25% of Latinos who received a nose swab test have seen a reduction in income, 15% have lost their jobs and 42% face food insecurity. Sixty-one percent of Mam (Mayan) speakers said they were food insecure.
 
“It is not new that we are the underserved and one of the most vulnerable groups in the area, and now with COVID-19 we are facing an even greater crisis especially with access to health services, housing, food and financial support. That is why we are here today, we are here to ask for more testing and assistance with essential needs,” Rosendo Aguilar, Fruitvale community member and Mam speaker, said in a statement.

UCSF study conducted a similar effort in San Francisco’s Mission District in April and found 95% of positive individuals were of Latino heritage.

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Antibody Treatment Becomes First FDA-Approved Medicine Against Ebola

The Food and Drug Administration (FDA) has approved the first treatment for Zaire ebolavirus (Ebola virus). The antibody medicine, called Inmazeb, is a cocktail of anti-viral antibodies made by Regeneron Pharmaceuticals to tackle the deadly disease, which continues to ravage the Democratic Republic of Congo (DRC).  

The novel treatment helps stave off the Zaire ebolavirus infection in both adult and young patients, and has been approved for widespread use after a large 2019 trial deemed it safe and effective at reducing mortality in infected patients. The medication, called REGN-EB3 (commercially Inmazeb), is most effective when administered early on during Ebola infection.

It will now be used alongside Merck’s Ervebo, the first FDA-approved vaccine for Ebola, as a two-pronged defense against the outbreaks seen across Africa.

“We are incredibly proud that the FDA has approved Inmazeb, which is also known as REGN-EB3. This is the first time the FDA has approved a treatment specifically for Ebola, which has caused a number of deadly outbreaks,” said George D. Yancopoulos, president and chief scientific officer of Regeneron, in a statement.

On June 1, 2020, the DRC announced its 11th outbreak of Ebola virus, which is still ongoing. As of September 2, the outbreak had taken the lives of 47 people. The 10th outbreak was the second largest on record and took the lives of 2,299 people within the DRC.

Inmazeb contains antibodies that bind directly to the Zaire ebolavirus and blocks the molecules that allow the virus particles to attach to the human cells. These molecules, called glycoproteins, bind to human cell receptors and provide a pathway for the virus to enter the cell, where it replicates and wages war on the immune system. Instead, the cocktail of antibodies contained in Inmazeb attach to the virus glycoprotein, blocking the binding site (epitope). By blocking this method of entry, the antibodies can prevent the virus from spreading and doing damage to host cells.

The medicine does have notable side effects, including fever, chills, tachycardia (fast heart rate), tachypnea (fast breathing), and vomiting. While these symptoms were related to Inmazeb, they are also symptoms of the Ebola virus and could have been directly related to the infection instead of the medicine.

Now, Regeneron hopes to provide the life-saving medication for free to people living under the current Ebola outbreak in the DRC, as part of the Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) protocol for compassionate use. The USA has also ordered Inmazeb in preparation for any potential public health emergencies in the future.

However, Inmazeb is not the only project Regeneron has been working on. You may recognize the name from a different antibody medicine (REGN-COV2) taken by US President Donald Trump during his battle with Covid-19. The company is still actively working toward a safe and effective Covid-19 treatment, and whilst the REGN-COV2 looks promising, it is still in the experimental phase.

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