 Your new post is loading...
|
Scooped by
Juan Lama
|
The global spread of SARS-CoV-2/COVID-19 is devastating health systems and economies worldwide. Recombinant or vaccine-induced neutralizing antibodies are used to combat the COVID-19 pandemic. However, recently emerged SARS-CoV-2 variants B.1.1.7 (UK), B.1.351 (South Africa) and B.1.1.248 (Brazil) harbor mutations in the viral spike (S) protein that may alter virus-host cell interactions and confer resistance to inhibitors and antibodies. Here, using pseudoparticles, we show that entry of UK, South Africa and Brazil variant into human cells is susceptible to blockade by entry inhibitors. In contrast, entry of the South Africa and Brazil variant was partially (Casirivimab) or fully (Bamlanivimab) resistant to antibodies used for COVID-19 treatment and was less efficiently inhibited by serum/plasma from convalescent or BNT162b2 vaccinated individuals. These results suggest that SARS-CoV-2 may escape antibody responses, which has important implications for efforts to contain the pandemic. Preprint available (Feb. 11. 2021): https://doi.org/10.1101/2021.02.11.430787
|
|
Scooped by
Juan Lama
|
Clinical setbacks reported this past week by Regeneron Pharmaceuticals and Eli Lilly have raised questions about the effectiveness of antibody therapies in patients with severe COVID-19 compared to patients with mild-to-moderate forms of the virus. Regeneron said Friday it agreed to hold off on further enrollment of patients requiring high-flow oxygen or mechanical ventilation in the Phase II/III portion (NCT04426695) of an adaptive Phase I/II/III trial assessing its two-antibody “cocktail” REGN-COV2 in hospitalized adult patients with COVID-19. In pausing enrollment of the sickest patients, Regeneron said it is following the recommendation of the trial’s independent data monitoring committee (IDMC) “based on a potential safety signal and an unfavorable risk/benefit profile at this time.” Regeneron did not disclose the potential safety signal that triggered the pause in patient enrollment—but did say it would inform the FDA of its findings, since the agency is evaluating the company’s request for an emergency use authorization (EUA) of REGN-COV2 for in mild-to-moderate outpatients at high risk for poor outcomes. Regeneron is the second developer of a leading antibody candidate against COVID-19 to suffer a clinical setback this past week. On October 26, the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) halted the up-to-10,000 patient Phase III ACTIV-3 trial (NCT04501978) it was conducting to assess the safety and effectiveness of Lilly’s LY-CoV555, recently renamed bamlanivimab, compared with Gilead Sciences’ Veklury™ (remdesivir) and placebo in people who have been hospitalized with COVID-19. “Disappointing replication” “A disappointing replication: monoclonal antibodies to #SARSCoV2 don’t provide benefit to hospitalized patients w/ moderate-severe illness,” tweeted Eric Topol, MD, founder and director of the Scripps Translational Research Institute, on Friday. Topol, who is also professor, molecular medicine and executive vice president of Scripps Research, added that the Regeneron and Lilly disappointments reflected “the need to treat #COVID19 early or preventatively.” Florian Krammer, PhD, professor at the department of microbiology, Icahn School of Medicine at Mount Sinai, also noted in a Twitter thread that early in COVID-19, monoclonal antibodies and other antivirals are likely to help infected patients. “Late in infection, our own immune system does the damage, and immunomodulatory drugs likely help at this stage (like dexamethasone),” Krammer said. “Using mAbs late (like in the trials stopped by Eli Lilly and Regeneron) was unlikely to work. But using them early is very promising.” Reflecting that promise, the IDMC in Regeneron’s hospitalized patient trial of REGN-COV2 also recommended continuing enrollment of the less severely injured hospitalized patients—namely those requiring either no or low-flow oxygen, “as the risk/benefit remains acceptable in these cohorts.” The trial has an estimated enrollment of 2,970 participants....
|
|
Scooped by
Juan Lama
|
U.S. President Donald Trump has received a promising but experimental COVID-19 drug still in clinical trials, according to a White House statement released Friday afternoon, following his diagnosis with the disease. Sean Conley, the President’s personal physician, wrote in a memo that he treated Trump with an eight-gram dose of Regeneron’s experimental antibody cocktail. Trump has also received zinc, vitamin D, aspirin, melatonin and a heartburn drug thought to help fight COVID-19. Regeneron on Tuesday announced promising results related to its monoclonal antibodies—drugs that mimic the human body’s natural immune response. When the body detects an infection, it deploys proteins called antibodies to help fight it off. Monoclonal antibodies essentially kickstart that process with synthetic proteins. In preliminary results from a trial of 275 non-hospitalized COVID-19 patients who were treated with either the antibody cocktail or a placebo, Regeneron’s cocktail reduced the amount of virus in patients’ systems and helped alleviate their symptoms, the company says. The therapy worked particularly well for patients whose immune systems failed to mount a natural response to SARS-CoV-2, the virus that causes COVID-19, according to Regeneron’s results. While those are promising results, they have yet to be peer-reviewed, and Regeneron’s therapy has not yet been cleared by the U.S. Food and Drug Administration. After the trial’s findings were released, executives said they planned to “rapidly” discuss them with the FDA, CNBC reports. Regeneron has enrolled participants for a larger study to confirm and build upon the results of its first trial. Trump is “fatigued but in good spirits” following his diagnosis with COVID-19, Conley wrote in his memo. He has reportedly experienced mild symptoms so far. First Lady Melania Trump, who also tested positive for the coronavirus, has a headache and mild cough, according to the memo. Trump is being taken to Walter Reed National Military Medical Center for a “few days,” the Associated Press reported late Friday afternoon.
|
|
Scooped by
Juan Lama
|
The world's largest randomised trial of potential medicines for COVID-19 is to add Regeneron's experimental antiviral antibody cocktail REGN-COV2 to the drugs it is testing in patients hospitalised with the disease. The UK RECOVERY trial, which has been testing a range of potential COVID-19 treatments since it began in April, will compare the effects of adding REGN-COV2 - a lab-manufactured monoclonal antibody - to standard care. “This is the first drug actually designed for this disease,” said Martin Landray, a professor of medicine & epidemiology at Oxford University who is co-leading the trial. “There are lots of good reasons for thinking this might be really quite a powerful treatment,” he told Reuters in an interview. The addition of Regeneron’s drug to the RECOVERY trial comes amid growing hopes that monoclonal antibodies may emerge as effective ways to treat COVID-19. Until now, the RECOVERY trial had mostly been studying whether existing drugs could be re-purposed to tackle the new disease, and it has already found answers on a number of them. In June and September, trial results showed that widely used steroids such as dexamethasone and hydrocortisone were able to reduce death rates among severely-ill COVID-19 patients. Also in June, RECOVERY trial results showed that the anti-malarial drug hydroxychloroquine, once touted by U.S. President Donald Trump as a potential “game changer” in the pandemic, was of no benefit in treating COVID-19 patients. Regeneron’s REGN-COV2 cocktail, which the company is already testing in late-stage clinical trials in people, combines one Regeneron-made antibody and a second antibody isolated from people who have recovered after being infected with COVID-19. The combination is designed to bind to the spike protein used by the new coronavirus to gain access to human cells, limiting the virus’s ability to escape. Regeneron developed the biological drug before linking up with Roche ROG.S to expand its manufacturing capacity in hopes of meeting global demand, should the medicine prove effective. Regeneron would handle U.S. sales, with Roche selling the medicine around the world. Landray said his team had secured enough supply of the drug so that up to “several thousand” patients could be given it in the trial and compared with several thousand controls. “Given that the second phase (of COVID-19 infections in the UK) seems to be coming now, it is a really good time to be starting this,” he said. The United States already has a $450 million deal for the cocktail in place, under the terms of which Regeneron will sell it around 70,000 to 300,000 potential treatment doses or 420,000 to 1.3 million prevention doses of REGN-COV2. Data is due later this month, Regeneron has said. Alongside Regeneron, Eli Lilly LLY.N, working with biotech firm AbCellera, is seen as a leading contender in the antibody race. In August it started testing whether its antibody can prevent COVID-19 infections in nursing homes. A separate trial testing the compound on recently diagnosed COVID patients may yield initial data in September or shortly after. GlaxoSmithKline GSK.L and partner Vir Biotechnology VIR.O also began testing an experimental antibody on newly diagnosed COVID-19 patients late last month. AstraZeneca AZN.L is for now testing its antibody-based cocktail on healthy volunteers for tolerability.
|
|
|
Scooped by
Juan Lama
|
Regeneron's therapy is part of a class of treatments known as monoclonal antibodies, which are made to act as immune cells that scientists hope can fight infections. The Food and Drug Administration on Saturday granted an emergency use authorization for Regeneron’s Covid-19 antibody treatment, the experimental therapy given to President Donald Trump when he contracted the coronavirus in October. Regeneron submitted an emergency use application that month after preclinical studies showed that the therapy, called REGN-COV2, reduced the amount of virus and associated damage in the lungs of non-human primates. The company said trial data also shows the drug reduces medical visits in patients with mild-to-moderate Covid-19. “The FDA remains committed to advancing the nation’s public health during this unprecedented pandemic. Authorizing these monoclonal antibody therapies may help outpatients avoid hospitalization and alleviate the burden on our health care system,” said FDA Commissioner Stephen M. Hahn. Regeneron’s therapy is part of a class of treatments known as monoclonal antibodies, which are made to act as immune cells that scientists hope can fight infections. Monoclonal antibody treatments gained widespread attention after news that Trump received Regeneron’s antibody cocktail. As Trump’s health improved, he touted it as a “cure.” But Regeneron’s CEO, Dr. Leonard Schleifer, has stressed that more testing is required. “Some people don’t know how to define therapeutic. I view it different. It’s a cure,” Trump said in a video posted Oct. 7 on Twitter. “For me, I walked in. I didn’t feel good. A short 24 hours later, I was feeling great. I wanted to get out of the hospital. And that’s what I want for everybody. I want everybody to be given the same treatment as your president because I feel great.” Regeneron’s authorization comes after the FDA announced on Nov. 9 that it had authorized Eli Lilly’s antibody treatment – called bamlanivimab –for people newly infected with Covid and are at risk of developing a severe form of the disease. Officials said the treatment shouldn’t be used for hospitalized patients because there is no data to show the drug is helpful at that stage of the disease. The authorization will expand the number of drugs at doctors’ disposal to fight the virus, which continues to rapidly spread across the United States and other parts of the world. Before the authorization, people could only get the drug as part of an FDA program that gives some patients limited access to investigational medical products. Gilead Sciences’ antiviral drug remdesivir is the first and only fully approved treatment in the U.S. for Covid. FDA Authorization Letter (Nov. 21, 2020): https://www.fda.gov/media/143891/download
|
|
Scooped by
Juan Lama
|
The company said that doses of the unproven treatment would be available for 50,000 patients. It’s impossible to know whether it helped the president. The drugmaker Regeneron said on Wednesday that it had submitted an application to the Food and Drug Administration for emergency approval of the experimental antibody cocktail that President Trump had praised just hours earlier without evidence as a “cure” for the coronavirus. The company said access to the treatment would be extremely limited at first, with only enough doses for 50,000 patients, a far cry from the “hundreds of thousands” of doses that Mr. Trump, in a video released on Wednesday, said he would soon be making available to Americans free of charge. In the five-minute video, Mr. Trump said that it was a “blessing from God” that he had been infected with the coronavirus and that the Regeneron cocktail had suddenly made him feel better. “I felt unbelievable,” he said. “I felt good immediately.” There is no evidence that the treatment is the reason he was feeling better, and his doctors have said he has taken other drugs as well. Mr. Trump gave the impression that he would push the F.D.A. to approve Regeneron’s treatment, even though the agency’s scientists are supposed to make independent decisions about approvals. “I have emergency-use authorization all set, and we’ve got to get it signed now,” Mr. Trump said. A spokeswoman for the F.D.A. declined to comment on Wednesday, saying the agency does not confirm or deny product applications. The news of Regeneron’s application on the same day that Mr. Trump effusively praised the unproven drug is likely to intensify fears that the president is pressuring federal health agencies to make decisions aimed at benefiting him politically. In the video, Mr. Trump repeated his desire to get a vaccine approved before the election on Nov. 3, even though the vaccine makers themselves have said that is highly unlikely...
|
|
Scooped by
Juan Lama
|
Experts caution more data from larger trials will be needed to know how potentially beneficial monoclonal antibodies are. New data from the biotechnology firm Regeneron seem likely to add to the excitement about drugs called monoclonal antibodies as treatments for Covid-19, but experts caution more data will be needed to know how potentially beneficial the medicines are. A high dose of the company’s antibody cocktail, REGN-COV2, led levels of the virus to decrease more quickly in infected, non-hospitalized patients, potentially indicating the treatment may help them get better, Regeneron reported Tuesday via press release. Full results will be published at a later date. “There’s nothing bad about these results, you just can’t say much about how transformative this is going to be,” said Eric Topol, director of the Scripps Research Translational Institute. As with data from a similar antibody, developed by Eli Lilly, he warned that the data so far should not be enough for the Food and Drug Administration to grant an emergency use authorization. “This doesn’t cut it, but it’s moving in the right direction, that’s for sure,” Topol said. In a notable finding, the data seem to show that the antibody had a bigger effect in patients who tested positive for SARS-CoV-2 but had not created high levels of their own antibodies against the virus. In this group, even a lower dose of the Regeneron antibodies seemed to result in patients getting better faster. The data add to the early results from Eli Lilly, which showed a reduction in virus levels for patients at some doses and a tantalizing hint that the treatment might help keep patients out of the hospital. Monoclonal antibodies are synthetic versions of one of the immune system’s own weapons against invaders. From the start of the pandemic, some experts have been most hopeful about this technology to create new medicines to fight SARS-CoV-2, the virus that causes Covid-19. But that potential could be limited by the ability to manufacture large quantities of the treatments. Regeneron has reached an agreement with Roche, the Swiss drug giant, to increase its production capacity. Experts said longer studies, which are ongoing, will be needed to really know if the antibody treatments make patients better. “We are highly encouraged by the robust and consistent nature of these initial data, as well as the emerging well-tolerated safety profile, and we have begun discussing our findings with regulatory authorities while continuing our ongoing trials,” said George Yancopoulos, Regeneron’s chief scientific officer. The data are from a 275-patient portion of Regeneron’s study testing REGN-COV2 in patients who have tested positive for Covid-19 but who are not in the hospital. Patients received either placebo, 2.4 grams of REGN-COV2, or 8 grams of REGN-COV2. (The antibody cocktail is delivered intravenously.) Those who received the high dose saw viral levels decrease by 0.60 log10 copies of the virus per milliliter compared to placebo after seven days, a result that was statistically significant. In the lower dose, there was a 0.23 log10 reduction, which was not statistically significant. Regeneron did not give the total amount of virus detected in its press release. At the beginning of the study, Regeneron tested patients not only to see if they had SARS-CoV-2, but also to see if they created their own antibodies against the virus. The company found that 45% of patients had created antibodies, 41% had not, and 14% had unclear results. Those without antibodies had higher levels of virus in swabs from their noses from the start. And those who had created their own antibodies got better much faster. Patients with their own antibodies in the placebo group saw symptoms disappear in seven days, while in those whom antibodies were not detected, it took 13 days for symptoms to go away. Giving the patients Regeneron’s synthetic antibody had a far greater effect on the amount of virus detected in those who did not have an antibody response before treatment. There was a reduction of 0.6 log10 copies/mL in the patients who received the high dose, and 0.51 in those who received the low dose, both of them statistically significant. The reductions were also greater in patients who had higher levels of virus. And in those patients who did not have detectable antibodies at the study’s outset, Regeneron’s antibody cocktail improved symptoms. In this group, symptoms were alleviated in 13 days on placebo, eight days in the high-dose group, and six days in the low-dose group. Among the 275 patients for whom data are being reported, 50% were Hispanic, 14% were African American, and the rest of the racial breakdown was not disclosed. On average, they were 45 years old. Forty-nine percent of participants were male and 51% were female... Regeneron's Press Release: https://investor.regeneron.com/news-releases/news-release-details/regenerons-regn-cov2-antibody-cocktail-reduced-viral-levels-and
|
