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Covid-19 vaccine from Pfizer and BioNTech shows positive results - STAT
It’s not yet clear whether the antibody levels produced will lead to immunity to the virus. To prove that, the companies will need to conduct large studies.
An experimental Covid-19 vaccine being developed by the drug giant Pfizer and the biotech firm BioNTech spurred immune responses in healthy patients, but also caused fever and other side effects, especially at higher doses. The first clinical data on the vaccine were disclosed Wednesday in a paper released on medRXiv, a preprint server, meaning it has not yet been peer-reviewed or published in a journal. We still have a ways to go and were testing other candidates as well, said Philip Dormitzer, the chief scientific officer for viral vaccines at Pfizers research laboratories. However, what we can say at this point is there is a viable candidate based on immunogenicity and early tolerability safety data. advertisement The study randomly assigned 45 patients to get one of three doses of the vaccine or placebo. Twelve received a 10-microgram dose, 12 a 30-microgram dose, 12 a 100-microgram dose, and nine a placebo. The 100-microgram dose caused fevers in half of patients; a second dose was not given at that level. Following a second injection three weeks later of the other doses, 8.3% of the participants in the 10-microgram group and 75% of those in the 30-microgram group developed fevers. More than 50% of the patients who received one of those doses reported some kind of adverse event, including fever and sleep disturbances. None of these side effects was deemed serious, meaning they did not result in hospitalization or disability and were not life-threatening. advertisement The vaccine generated antibodies against SARS-CoV-2, the virus that causes Covid-19, and some of these antibodies were neutralizing, meaning that they appear to prevent the virus from functioning. Levels of neutralizing antibodies were 1.8 to 2.8 times the level of that in the recovered patients. Its not certain that higher antibody levels will lead to immunity to the virus. To prove that, Pfizer will need to conduct large studies that aim to prove that people who have received the vaccine are at least 50% less likely to become infected. Those studies are expected to begin this summer, mostly in the United States. Pfizer is testing four different versions of the vaccine, but only one will advance to larger studies. The current study did not include pregnant women, and no other information on the ethnic diversity of participants was noted, although the paper does say that future studies will need to include a more diverse group. The second dose, a booster shot, was required for immunity. The patients who received the single 100-microgram dose had lower antibody levels than those who received two shots of the lower doses. Fourteen Covid-19 vaccines are currently in human trials, according to the Milken Institute, including entrants from Inovio, CanSino, AstraZeneca, and Moderna. More are expected to start soon, including entrants from Merck, Johnson & Johnson, and Sanofi. In total, 178 vaccines are in various stages of development. The Pfizer/BioNTech vaccine, like the Moderna vaccine, is based on a technology called messenger RNA, which uses a key genetic messenger found in cells to create protein that the immune system then learns to attack. Moderna has not yet published data on its vaccine but is expected to do so soon.
New study likely closes door on use of hydroxychloroquine for Covid-19 - STAT
A major clinical trial showed the malaria drug hydroxychloroquine had no benefit for patients hospitalized with Covid-19.
A major clinical trial showed the malaria drug hydroxychloroquine had no benefit for patients hospitalized with Covid-19, likely closing the door to the use of the highly publicized medicine in the sickest patients a use for which it was widely prescribed as the pandemic hit the U.S. The results come from a study called RECOVERY, funded by the U.K. government, that sought to randomly assign large numbers of patients to multiple potential treatments in the countrys National Health Service. The goal was to rapidly get answers as to what worked and what didnt. Todays preliminary results from the RECOVERY trial are quite clear hydroxychloroquine does not reduce the risk of death among hospitalized patients with this new disease, University of Oxford epidemiologist Martin Landray, one of the studys leaders, said in a statement. This result should change medical practice worldwide and demonstrates the importance of large, randomized trials to inform decisions about both the efficacy and the safety of treatments. advertisement A total of 1,542 received hydroxychloroquine, and 3,132 received usual care. After 28 days of treatment, 25.7% of those on hydroxychloroquine and 23.5% of those received usual care had died, meaning those on hydroxychloroquine were 11% more likely to die. That difference was not statistically significant. There was no beneficial effect on how long patients stayed in the hospital, or on other outcomes. advertisement The results were shared via a press release, which the studys lead authors shared on Twitter. They have not been peer-reviewed or published in a medical journal. The researchers said that full results would be shared as soon as possible. Still, experts said even the top-line results showed they were meaningful. This is a hugely important finding that will likely end use of the drug in hospitalized Covid patients, given the other existing data as well, said Walid Gellad, director of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh. Gellad said that he is curious to see the results of other ongoing studies, and that it is still an open question whether the medicine might work earlier in the disease. We need real answers there as well, he said. Robert Califf, the former Food and Drug Administration commissioner and Alphabet employee, tweetedthat the study essentially rules out benefit of [hydroxychloroquine] in critically ill hospitalized patients. He wrote that the results showed no benefit; no major risk. In addition to being used for malaria, hydroxychloroquine is prescribed to treat conditions including rheumatoid arthritis and lupus. But it was known to increase the risk of arrhythmias. The FDA still authorized emergency use of the drug in hospitalized patients in March, citing the possible safety issues. Concerns were heightened by a May 22 study in British medical journal the Lancet. That study, which claimed to use a database from hundreds of hospitals around the world, seemed to indicate that treatment with hydroxychloroquine increased the death rate and the rate of arrhythmias. But on Thursday, the Lancet retracted that study at the request of the authors after widespread questions about the database the study used and the company, Surgisphere, that had provided it. The authors not associated with Surgisphere had asked for the data to be audited, and Surgisphere refused. As such, they wrote, we can no longer vouch for the veracity of the primary data sources. On Wednesday, another group of researchers released results from another randomized study, testing whether giving people hydroxychloroquine shortly after they have been exposed to someone with Covid-19 could prevent disease transmission. That study also showed no benefit, thought some researchers, including Gellad and Califf, say some effect is still possible. It could still have an effect given very early in disease, although less and less likely every day that passes, Gellad said. There are dozens of studies ongoing with hydroxychloroquine, more than for any other potential Covid-19 treatment, including studies that combine it with antibiotics such as azithromycin or doxycycline. But the results appear to show the benefit of putting resources into testing medicines in large randomized trials, the medical gold standard, during a pandemic. The RECOVERY trial represented an early and large effort at such studies, testing not only hydroxychloroquine but also a pair of HIV drugs, lopinavir and ritonavir, and the steroid dexamethasone. The study was later expanded to also test using plasma from recovered patients to treat those who are still ill.
Lancet, NEJM retract Covid-19 studies that sparked backlash - STAT
The journals said the authors of the paper were unable to complete an independent audit of the data underpinning their analyses.
The Lancet, one of the worlds top medical journals, on Thursday retracted an influential study that raised alarms about the safety of the experimental Covid-19 treatments chloroquine and hydroxychloroquine amid scrutiny of the data underlying the paper. Just over an hour later, the New England Journal of Medicine retracted a separate study, focused on blood pressure medications in Covid-19, that relied on data from the same company. The retractions came at the request of the authors of the studies, published last month, who were not directly involved with the data collection and sources, the journals said. advertisement We can no longer vouch for the veracity of the primary data sources, Mandeep Mehra of Brigham and Womens Hospital, Frank Ruschitzka of University Hospital Zurich, and Amit Patel of University of Utah said in a statement issued by the Lancet. Due to this unfortunate development, the authors request that the paper be retracted. The retraction of the Lancet paper is sure to add fuel to contentious arguments about the potential of chloroquine and hydroxychloroquine, two old malaria drugs, in Covid-19, the disease caused by the novel coronavirus. President Trump has touted them as valuable treatments, despite a lack of rigorous data showing they have a benefit. advertisement Meanwhile, on Wednesday, researchers reported the results of the first gold-standard clinical trial of hydroxycholoroquine in Covid-19, concluding that it did not prevent infections any better than placebo. Other clinical trials, including some looking at the drugs as treatments, are ongoing. The Lancet study gained so much attention because it went further than other observational studies that had similarly found the drugs were not associated with improved outcomes for patients. The study, which was purportedly based on patient data from 671 hospitals on six continents, reported the drugs also corresponded to higher mortality. The findings led to the pause of some global clinical trials studying hydroxychloroquine so researchers could check for any safety concerns. Outside experts, however, quickly raised concerns after noticing inconsistencies in the data. They asked the company that compiled and analyzed the data, Surgisphere, to explain how it sourced its data. As scrutiny grew, the authors on the paper not affiliated with Surgisphere called for an independent audit. In their Lancet statement Thursday, they said that Surgisphere was not cooperating with the independent reviewers and would not provide the data. As such, our reviewers were not able to conduct an independent and private peer review and therefore notified us of their withdrawal from the peer-review process, the researchers wrote. Outside experts raised similar concerns about the New England Journal study, which found that the blood pressure medications were safe to take for people with Covid-19. It was also based on data from Surgisphere. In the New England Journal retraction statement, the study authors wrote, Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article. They apologized for the difficulties that this has caused. Concerns about the health risks of chloroquine and hydroxychloroquine were based on evidence beyond the Lancet paper. Earlier, the Food and Drug Administration warned the drugs should not be used in Covid-19 outside a clinical trial or beyond hospitalized patients because of the risks to heart health. The drugs are safe for people to take for malaria, rheumatoid arthritis, and lupus, for whom they are shown to have benefits, experts stress.