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Juan Lama
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Background The first COVID-19 vaccine outside a clinical trial setting was administered on Dec 8, 2020. To ensure global vaccine equity, vaccine targets were set by the COVID-19 Vaccines Global Access (COVAX) Facility and WHO. However, due to vaccine shortfalls, these targets were not achieved by the end of 2021. We aimed to quantify the global impact of the first year of COVID-19 vaccination programmes. Methods A mathematical model of COVID-19 transmission and vaccination was separately fit to reported COVID-19 mortality and all-cause excess mortality in 185 countries and territories. The impact of COVID-19 vaccination programmes was determined by estimating the additional lives lost if no vaccines had been distributed. We also estimated the additional deaths that would have been averted had the vaccination coverage targets of 20% set by COVAX and 40% set by WHO been achieved by the end of 2021. Findings Based on official reported COVID-19 deaths, we estimated that vaccinations prevented 14·4 million (95% credible interval [Crl] 13·7–15·9) deaths from COVID-19 in 185 countries and territories between Dec 8, 2020, and Dec 8, 2021. This estimate rose to 19·8 million (95% Crl 19·1–20·4) deaths from COVID-19 averted when we used excess deaths as an estimate of the true extent of the pandemic, representing a global reduction of 63% in total deaths (19·8 million of 31·4 million) during the first year of COVID-19 vaccination. In COVAX Advance Market Commitment countries, we estimated that 41% of excess mortality (7·4 million [95% Crl 6·8–7·7] of 17·9 million deaths) was averted. In low-income countries, we estimated that an additional 45% (95% CrI 42–49) of deaths could have been averted had the 20% vaccination coverage target set by COVAX been met by each country, and that an additional 111% (105–118) of deaths could have been averted had the 40% target set by WHO been met by each country by the end of 2021. Interpretation COVID-19 vaccination has substantially altered the course of the pandemic, saving tens of millions of lives globally. However, inadequate access to vaccines in low-income countries has limited the impact in these settings, reinforcing the need for global vaccine equity and coverage. Funding Schmidt Science Fellowship in partnership with the Rhodes Trust; WHO; UK Medical Research Council; Gavi, the Vaccine Alliance; Bill & Melinda Gates Foundation; National Institute for Health Research; and Community Jameel. Published in The Lancet Infectious Diseases (June 23, 2022):
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Juan Lama
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Regeneron Pharmaceuticals is planning to ask the Food and Drug Administration (FDA) to allow its antibody cocktail to be used as a preventive treatment for COVID-19, the company said Monday. New results from a clinical trial conducted with the National Institute of Allergy and Infectious Diseases found the drug reduced the risk of symptomatic infection by 81 percent in people who were not infected at the start of the trial, Regeneron said. The company has already received emergency use authorization from the FDA to use its antibody drugs to treat adults with mild to moderate COVID-19 and pediatric patients at least 12 years old who have tested positive for the virus and are at high risk of severe disease but are not yet hospitalized. The trial enrolled 1,505 people who were not infected with the virus but lived in the same household as someone who recently tested positive. The patients were randomized to receive either one dose of the antibody therapy or a placebo administered as injections. After 29 days, 11 people out of the 753 who received a single 1,200 mg dose of the treatment developed symptomatic COVID-19; 59 people who received a placebo out of 752 participants developed symptomatic COVID-19. The drug provided 72 percent protection against symptomatic infections in the first week and 93 percent protection in subsequent weeks, Regeneron said. The data has not yet been peer reviewed or published. Regeneron also said the trial found individuals treated with the therapy who experienced a symptomatic infection resolved their symptoms in one week, compared to three weeks with placebo. Infected individuals also cleared the virus faster with the therapy, the company said. Adverse events occurred in 20 percent of patients who received the antibody drug and 29 percent of those who received a placebo, Regeneron said, but nobody withdrew from the trial because of them. None of the participants who received the therapy were hospitalized or went to the ER because of COVID-19 over the course of 29 days; four in the placebo group did so. There were four deaths in the trial — two in the therapy group and two in the placebo group — but none were reported due to COVID-19 or the drug. "With more than 60,000 Americans continuing to be diagnosed with COVID-19 every day, the REGEN-COV antibody cocktail may help provide immediate protection to unvaccinated people who are exposed to the virus, and we are also working to understand its potential to provide ongoing protection for immunocompromised patients who may not respond well to vaccines," George Yancopoulos, president and chief scientific officer at Regeneron, said in a statement. Regeneron's Press Release (April 12, 2021): https://investor.regeneron.com/news-releases/news-release-details/phase-3-prevention-trial-showed-81-reduced-risk-symptomatic-sars
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Juan Lama
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The spread of the COVID-19 virus is highly variable among U.S. counties. Seventeen factors known or thought to be related to spread of the COVID-19 virus were studied by Poisson regression analysis of confirmed cases and deaths in 883 U.S. counties with a population of 50,000 or more as of May 31, 2020. With little exception, each factor was predictive of incidence and mortality. Most of the correlations are as expected but the lower numbers of cases in counties with a larger percentage of Hispanics in the population is contrary to claims that Hispanics work disproportionately in industries where the virus spread rapidly. Similarly, the finding that the cases and deaths are more frequent in counties with higher median incomes may seem counter to the evidence that people with lower incomes are more likely to be exposed to the virus. Again the correlation prevails after controlling for other factors such as unemployment. Recall that one of the early hotspots was Westchester County New York, one of the wealthiest counties in the U.S. It is likely that air travel and business meetings increased risk among more affluent people. The regression equation can be used to identify priority locations for preventive efforts and preparation for medical care caseloads when prevention is unsuccessful. Based on the correlation of cases and deaths to days since stay-at-home orders were issued, the orders reduced the cases about 48 percent and deaths about 50 percent. The shutdowns probably prevented about 1.4 million cases and 92,000 deaths. The study that claimed the warnings and shutdowns prevented 60 million COVID-19 cases in the U.S. appears to be grossly inflated by a factor of 40. Focusing preventive efforts on the more vulnerable counties may be more effective and less economically damaging than statewide shutdowns. Preprint available at medRxiv (June 26, 2020): https://doi.org/10.1101/2020.06.25.20139956
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Juan Lama
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The U.S. Food and Drug Administration (FDA) approved Gilead Science's Descovy for HIV pre-exposure prophylaxis (PrEP). Descovy is a doublet combination of 200 mg of emtricitabine and 25 mg of tenofovir alafenamide. It was not approved, however, for at-risk individuals from receptive vaginal sex because it hasn’t been tested for that indication. Descovy was approved for this indication under the FDA’s priority review designation. The drug also carries a Boxed Warning in the U.S. because of the risk of post treatment acute exacerbation of hepatitis B. It also includes a Boxed Warning over the risk of drug resistance with PrEP use in undiagnosed early HIV-1 infection. The supplemental New Drug Application (sNDA) was built on the DISCOVER Phase III clinical trial results. This trial evaluated more than 5,300 adult cisgender men who have sex with men or transgender women who have sex with men. The primary efficacy endpoint was the incidence of documented HIV infection per 100 person-years after follow-up for at least 48 weeks and at least half of the group had a follow-up at 96 weeks. “Descovy for PrEP provides a new HIV prevention option that matches Truvada’s high efficacy with statistically significant improvements in renal and bone safety, which can be an important consideration as people at risk increasingly use PrEP for longer periods of time,” said Daniel O’Day, chairman and chief executive officer of Gilead. “This is a reflection of Gilead’s continued commitment to addressing the evolving needs of people living with or at risk for HIV and to driving innovation across the HIV care continuum.” The only other drug currently approved in the U.S. for HIV PrEP is Gilead’s Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg). In the DISCOVER trial, Descovy was found to be noninferior to Truvada in terms of efficacy for this patient population, and there were significant advantages over Truvada for six pre-specified secondary endpoints related to renal and bone laboratory parameters. “PrEP drugs are highly effective when taken as indicated in the drug labeling and can prevent HIV infection,” stated Jeffrey Murray, deputy director of the Division of Antiviral Products in the FDA’s Center for Drug Evaluation and Research. “This approval provides more prevention options for certain patients at-risk for acquiring HIV and helps further efforts by the FDA and the U.S. Department of Health and Human Services to facilitate the development of HIV treatment and prevention options to reduce new HIV infections.” HIV PrEP has come with some controversy. Truvada runs about $20,000 a year. A generic version is expected to hit the market in 2020. The Trump Administration has indicated it wants to increase access to PrEP as part of its efforts to end HIV transmission by 2030. However, in a U.S. House of Representatives hearing in May, O’Day took some heat for the price of the drug that had some government research funding. Summary of Results of DISCOVER Trial: https://www.gilead.com/news-and-press/press-room/press-releases/2019/3/gilead-announces-data-demonstrating-noninferiority-of-oncedaily-descovy-vs-oncedaily-truvada-for-prevention-of-hiv-infection
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Juan Lama
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Pfizer on Friday said a large trial found that its COVID-19 oral antiviral treatment Paxlovid was not effective at preventing coronavirus infection in people living with someone who had been exposed to the virus. The trial enrolled 3,000 adults who were household contacts exposed to an individual who was experiencing symptoms and had recently tested positive for COVID-19. They were either given Paxlovid for five or 10 days or a placebo. Those who took the five-day course were found to be 32 per cent less likely to become infected than the placebo group. That rose to 37 per cent with 10 days of Paxlovid. However, the results were not statistically significant and thus possibly due to chance. Pfizer said safety data in the trial was consistent with previous studies, which had shown the pills to be nearly 90 per cent effective at preventing hospitalization or death in COVID patients at high risk of severe illness when taken for five days shortly after symptom onset. “While we are disappointed in the outcome of this particular study, these results do not impact the strong efficacy and safety data we’ve observed in our earlier trial for the treatment of COVID-19 patients," Pfizer Chief Executive Albert Bourla said in a statement. Pfizer said Paxlovid, which consists of two different antiviral drugs, is currently approved or authorized for conditional or emergency use in more than 60 countries across the globe to treat high-risk COVID-19 patients. Sales of Paxlovid, part of a class of drugs known as protease inhibitors, are projected to reach $24 billion this year, according to Wall Street forecasts compiled by Refinitiv. Shares of Pfizer, which fell 3 per cent in regular trading, were down another 1 per cent at $48.53 after hours. (Reporting By Deena Beasley. Editing by Bill Berkrot) Pfizer Press Release (April 29, 2022): https://www.pfizer.com/news/press-release/press-release-detail/pfizer-shares-top-line-results-phase-23-epic-pep-study
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Juan Lama
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The studies were run on a total of 36 rhesus macaques and 50 hamsters. The company is careful to caution that positive animal studies do not guarantee success in humans. In early July, Regeneron Pharmaceuticals, with the U.S. National Institute of Allergy and Infectious Diseases (NIAID), announced they were launching Phase III trials of REGN-COV-2, the company’s two-antibody cocktail to treat and prevent COVID-19. Although those results of those trials are still pending, the company issued a scientific article, not yet peer-reviewed, that shows the cocktail was able to “almost completely block establishment of virus infection,” in rhesus macaques and hamsters. Using its proprietary VelocImmune mice, Regeneron screened thousands of fully-human antibodies. The mice have been genetically modified to have a human immune system. They also evaluated antibodies isolated from people who have recovered from COVID-19. They then chose the two most potent, non-competing antibodies that were most effective at neutralizing SARS-CoV-2, the virus that causes COVID-19. They then scaled up the dual-antibody cocktail for clinical use with the company’s own VelociMab and manufacturing capabilities. The two antibodies bind non-competitively to the receptor binding domain of the virus’s spike (S) protein. This decreases the ability of mutant viruses to avoid treatment and protects against spike variants that have evolved in the human population. On June 11, the company announced the publication of two scientific articles describing the effectiveness of REGN-COV-2 in the journal Science. The first paper was, “Studies in humanized mice and convalescent humans yield a SARS-COV-2 antibody cocktail.” In the latest animal study paper, the authors said the cocktail in monkeys and hamsters demonstrated “that REGEN-COV-2 can greatly reduce virus load in lower and upper airway and decrease virus-induced pathological sequelae when administered prophylactically or therapeutically. Our results provide evidence of the therapeutic potential of this antibody cocktail.” Essentially, the study took two approaches. One was to infect animals with the virus, then dose them with the antibody cocktail to see if it could halt the infection. It appeared to do this successfully. The second approach was to dose the animals with the antibody cocktail, then infect them with the virus. This also appeared to prevent infection. It’s important to note that the antibody cocktail is not a vaccine. Therapeutic antibodies such as these do not have long-range effects, although they may last several months. The studies were run on a total of 36 rhesus macaques and 50 hamsters. The company is careful to caution that positive animal studies do not guarantee success in humans. The human trials have already started. There are specifically two trials. A Phase III trial will study if REGN-COV-2 can prevent infection in uninfected people who have had close exposure to a COVID-19 patient. The drug has also been advanced into the Phase II/III portion of two adaptive Phase I/II/III trials evaluating the cocktail in treating hospitalized and non-hospitalized patients with COVID-19.... Preprint available at bioRxiv (August 3, 2020): https://doi.org/10.1101/2020.08.02.233320
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Juan Lama
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HPTN 083 is the first study to compare the efficacy of CAB LA to daily oral TDF/FTC for HIV PrEP. HPTN 083 enrolled 4,570 cisgender men who have sex with men (MSM) and transgender women (TGW) who have sex with men at 43 sites in Argentina, Brazil, Peru, United States, South Africa, Thailand and Vietnam. For many people, taking a daily pill can be challenging. The development of safe and effective long acting alternative agents for HIV PrEP would increase HIV prevention choices and help those who find taking a daily pill challenging. Some people also may find periodic injections to be a more discreet form of HIV PrEP than daily pills and may prefer CAB LA for that reason. Participants were assigned randomly (by chance) to either the CAB or oral TDF/FTC group. Neither the participants nor the study team knows who was in which group. Participants in each group received both injections and oral tablets – each participant received one active drug and one placebo (no active drug) in order to maintain the blinded nature of the study. Participants were randomized to one of two study arms and included three steps: Step 1 consisted of 5 weeks of daily oral CAB and a TDF/FTC placebo or 5 weeks of daily oral TDF/FTC and an oral CAB placebo; Step 2 consisted of 148 weeks of intramuscular CAB LA 600 mg every 8 weeks plus daily oral TDF/FTC placebo or 148 weeks of daily oral TDF/FTC plus an intramuscular CAB LA placebo every 8 weeks ; and Step 3 consisted of an open-label daily oral TDF/FTC for 48 weeks after participants completed Step 2. On May 14, 2020 a Data and Safety Monitoring Board (DSMB) reviewed HPTN 083 study data and recommended that the blinded part of the study be stopped early for successfully meeting its specified objectives. The study results showed that CAB LA, administered every eight weeks, provided high efficacy compared to TDF/FTC. A total of 50 incident HIV infections occurred in HPTN 083, with 38 incident HIV infections in the TDF/FTC arm (incidence rate 1.21%) and 12 incident HIV infections in the CAB arm (incidence rate 0.38%): in other words, approximately three times the number of incident HIV infections were in the TDF/FTC arm than in the CAB arm. The study sponsor, the U.S. National Institute of Allergy and Infectious Diseases (NIAID), approved the decision to stop the blinded part of the study.
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