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October 14, 2020

Safety concerns pause clinical trials for J&J, Eli Lilly coronavirus drugs

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    Johnson & Johnson (J&J) on Monday announced that it has paused dosing in all of its clinical trials on its experimental coronavirus vaccine to investigate an "unexplained illness in a study participant." Separately, NIH on Tuesday announced that it has paused a clinical trial on Eli Lilly's experimental coronavirus treatment due to potential safety issues.

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    US new coronavirus cases near 7.9M, deaths approach 216K

    The announcements came as U.S. officials as of Wednesday morning reported a total of 7,894,900 cases of the novel coronavirus since the country's epidemic began—up from 7,840,388 cases reported as of Tuesday.

    According to the New York Times, the United States' average daily number of newly reported coronavirus cases over the past week was 52,156—which is up by 21% when compared with the average from two weeks ago.

    Data from the Times shows that the rates of newly reported coronavirus cases are "staying high" in Guam and 27 states that have had a daily average of at least 15 newly reported cases per 100,000 people over the past week. Those states are Alabama, Alaska, Arkansas, Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada, New Mexico, North Carolina, North Dakota, Oklahoma, Rhode Island, South Carolina, South Dakota, Tennessee, Texas, Utah, Wisconsin, and Wyoming.

    Washington, D.C., and 18 states that have had comparatively low case rates are now seeing those rates "going up," according to the Times. Those states are Arizona, Colorado, Connecticut, Delaware, Louisiana, Maryland, Massachusetts, Michigan, New Hampshire, New Jersey, New York, Ohio, Oregon, Pennsylvania, Vermont, Virginia, Washington, and West Virginia.

    In the seven remaining U.S. states and territories, rates of newly reported coronavirus cases are "staying low," according to the Times' analysis.

    U.S. officials as of Wednesday morning also reported a total of 215,781 deaths linked to the coronavirus since the country's epidemic began—up from 214,955 deaths reported as of Tuesday.

    J&J pauses recruitment, dosing for its vaccine trials

    J&J on Sept. 23 began enrolling participants in its placebo-controlled, Phase 3 clinical trial—called ENSEMBLE—on its experimental coronavirus vaccine candidate. The company aimed to enroll up to 60,000 participants in the trial in the United States and other countries, the Wall Street Journal reports.

    However, J&J on Monday announced that it has temporarily stopped recruiting new volunteers for the clinical trial and has paused dosing in the trial, because a participant has developed an unexplained illness. J&J did not provide additional information about the illness or the affected participant. The company in a statement said, "We must respect this participant's privacy. We're also learning more about this participant's illness, and it's important to have all the facts before we share additional information."

    J&J also said that "[a]dverse events … are an expected part of any clinical study, especially large studies," and the company noted that, in placebo-controlled trials, "it is not always immediately apparent whether a participant received a study treatment or a placebo."

    J&J explained that it has "prespecified guidelines" to ensure its clinical trials "may be paused if an unexpected serious adverse event … that might be related to a vaccine or study drug is reported." Under J&J's guidelines, the company may pause a trial for many reasons, including because of instances in which a trial participant has a serious adverse event found to be related to the vaccine or drug being studied and instances in which a participant has a severe allergic reaction or hives that cannot be linked to anything other than the vaccine or drug being studied, the Journal reports.

    J&J said pausing ones of its clinical trials allows the company to conduct "a careful review of all of the medical information before deciding whether to restart [a] study."

    According to a document obtained by STAT News, J&J notified researchers administering the clinical trial that criteria for pausing the trial had been met, and that the company's online system for enrolling patients in the trial had been closed. The document also stated that the trial's data and safety monitoring board—which is an independent committee responsible for monitoring the safety of trial participants—would convene.

    J&J in its announcement said the board and the company's "internal clinical and safety physicians" are reviewing and evaluating the participant's illness.

    J&J's announcement comes after AstraZeneca last month paused its Phase 3 clinical trials for its coronavirus vaccine candidate, after an AstraZeneca trial participant in the United Kingdom developed an unexplained illness. AstraZeneca since has resumed its Phase 3 clinical trial on the coronavirus vaccine candidate in the United Kingdom, after regulators determined it was safe to do so. However, the company's coronavirus vaccine trials in the United States remain on hold, the Journal reports.

    AstraZeneca and J&J are among just a handful of pharmaceutical companies, including Moderna and Pfizer, that are testing coronavirus vaccine candidates in late-stage clinical trials in the United States. J&J's experimental inoculation, which the company co-developed with Beth Israel Deaconess Medical Center, is among the most advanced vaccine candidates to date, the Journal reports.

    J&J has noted that a pause is different than a clinical hold, which is a formal regulatory action that can last longer than a pause. On Tuesday, J&J CFO Joseph Wolk said the company's clinical trial currently is "in the hands of the independent drug-safety monitoring board." He added that the incident is "still under investigation, and [J&J is] going to let that process play out."

    NIH pauses clinical trial testing Eli Lilly's antibody treatment

    Separately, NIH on Tuesday announced that it has paused a clinical trial testing Eli Lilly's antibody treatment for Covid-19 because of a "potential safety concern," according to emails sent by government officials to researchers at the trial's testing sites, the Times reports.

    The placebo-controlled trial—which is sponsored by NIH, Veterans Affairs, and other organizations—is designed to evaluate the effects of Eli Lilly's monoclonal antibody, called LY-CoV555, on hundreds of hospitalized Covid-19 patients. The trial's investigators, who are responsible for registering and treating the study's participants, had enrolled 326 participants in the study to date. Participants in the trial's treatment and placebo arms all received Gilead Sciences' antiviral drug remdesivir, which is considered a standard of care for Covid-19.

    NIH said that, on Tuesday morning, the trial's independent data safety monitoring board recommended the trial be paused because the group of participants who had received Eli Lilly's antibody drug for five days showed a different "clinical status" than the group of participants who had received a saline placebo. NIH said that difference crossed a "predefined boundary for safety," but the agency did not provide details on the clinical status of the trial's participants.

    In addition, government officials in directed the trial's investigators to stop enrolling volunteers in the study out of "an abundance of caution."

    NIH said the trial's investigators will continue to monitor the trial's participants, and the trial's data safety monitoring board will meet again on Oct. 26 to decide whether to resume the study.

    According to the STAT News, a data safety monitoring board may recommend stopping a trial for several reasons. For example, the board may decide to stop a trial if patients are at risk or a treatment clearly works, or if an answer on a treatment's effects is unlikely to emerge, STAT News reports. The board also may choose to stop a trial if a treatment's chances of working are low based on the available data or if there's evidence showing one group of participants enrolled in a trial is faring better than the other.

    In a statement emailed to the Times, Molly McCully, Eli Lilly's spokesperson, confirmed the pause.

    "Safety is of the utmost importance to Lilly," McCully wrote. "Lilly is supportive of the decision by the independent [data safety monitoring board] to cautiously ensure the safety of the patients participating in this study" (Lim, Politico, 10/12; Herper, STAT News, 10/12; Loftus, Wall Street Journal, 10/12; J&J release, 10/12; Garde/Herper, STAT News, 10/13; Wu/Thomas, New York Times, 10/13; Griffin, Bloomberg, 10/13; New York Times, 10/14).

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