BREAKING NEWS! Eli Lily’s Antibody Clinical Trial Suddenly Halted Without Reasons. Sources Say Severe Adverse Reactions In Trial Participants
The Antibody Clinical Trial
called ACTIV-3 clinical trial involving a combination of antibodies against COVID-19 has been suddenly halted over safety concerns yesterday. No details were furnished to the media or medical community.
A stoppage in trial would typically be because a patient or volunteer showed a serious side effect or became sick, but the company did not clarify what the reason for the pause is. The pause appears to refer to the
“Safety is of the utmost importance to Lilly,” the company told certain media by email.
It was reported that an independent Data Safety Monitoring Board (DSMB) has recommended the pause.
Anonymous sources involved with the clinical trial said that there were a number of participants in the trial who had developed adverse reactions and the treatment did not seem to benefit certain infected COVID-19 patients.(Thailand Medical News cannot confirm the validity of these statements but will provide details once verified facts emerge as to the actual reasons for the stoppage of the clinical trial)
The pharmaceutical company added, “The trial, evaluating Lilly’s investigational neutralizing antibody as a treatment for COVID-19 in hospitalized patients, is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). Lilly is supportive of the decision by the independent DSMB to cautiously ensure the safety of the patients participating in this study.”
Interestingly on September 16, Eli Lilly announced interim proof-of-concept data from its BLAZE-1 Phase II trial of LY-COV555, its neutralizing antibodies, singly or in combination against COVID-19. That study enrolled mild-to-moderate COVID-19 patients who had recently been diagnosed in the outpatient setting and received either placebo, 700 mg, 2800 mg and 7000 mg of the antibody.
However many researchers are questioning the use of single antibodies due to the quick rise of single antibody resistance typical in most coronaviruses.
In that clinical trial, the cocktail protocol however reduced
viral load, symptoms and COVID-related hospitalization and ER visits. The trial was of LY-CoV555 and LY-CoV016, which bind different but complementary regions of the SARS-CoV-2 spike protein. The combination cohort enrolled recently diagnosed patients with mild-to-moderate COVID-19. These patients received either 2800 mg of each antibody or placebo.
On the 7th
of October 7, Lilly updated news on the antibody programs, with the company stating, “Combination therapy has been generally well tolerated with no drug-related serious adverse events.”
Interestingly in LY-COV555 monotherapy studies there have been isolated drug-related infusion reactions or hypersensitivity that were generally mild (two reported as serious infusion reactions, all patients recovered). Treatment emergent adverse events were comparable to placebo for both LY-CoV555 monotherapy and combination therapy.
Lily’s announcement yesterday would suggest that
the DSMB saw something in the data to require a pause. It’s important to note that a trial pause is different than a clinical hold, with a clinical hold being a formal regulatory order that typically lasts longer. Pauses are very common in clinical trials, normally, but because of the heightened attention being paid to therapeutics and vaccines against COVID-19, are being made public.
The day before yesterday, Johnson & Johnson paused its clinical trial of its COVID-19 vaccine due to “an unexplained illness in a study participant” as well. J&J began
its Phase III trial of JNJ-78436735 on September 23. The vaccine was developed by J&J’s Janssen Pharmaceutical Companies using its AdVac technology platform, which was also used to develop Janssen’s Ebola vaccine that was approved in Europe and to develop its Zika, RSV, and HIV vaccine candidates. The Phase III ENSEMBLE trial will evaluate the vaccine’s safety and efficacy compared to placebo in up to 60,000 adults ages 18 and older. It is enrolling volunteers in the U.S., Argentina, Brazil, Chile, Colombia, Mexico, Peru and South Africa.
Johnson and Johnson did not disclose much information about the unexplained illness, stating, “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.”
The pharma giant company also emphasized that adverse events are part of most clinical trials and that this is a “study pause” instead of a “clinical hold,” which is a formal regulatory action. A “clinical hold” can last much longer than a “study pause.” Normally, J&J indicated they would not announce study pauses to the public, but due to the overwhelming interest in the study and the urgency involved because of the COVID-19 pandemic, felt the need to release the information.
The Eli Lilly and NIAID’s ACTIV-3 study was to b
egin evaluating LY-CoV555. The antibody was discovered by Abcellera Biologics in collaboration with NIAID’s Vaccine Research Center. It was then developed and manufactured by Lilly Research Laboratories in partnership with AbCellera.
The ACTIV-3 trial also testing
the monoclonal antibody in combination with Gilead Sciences’ remdesivir.
The protocol is also being evaluated in another ongoing NIAID trial, ACTIV-2, which is studying its safety and efficacy in people with mild to moderate symptoms of COVID-19 who have not been hospitalized. The DSMB has access to shared data across both studies.
COVID-19 antibody therapies have been front-and-center since President Trump was treated with Regeneron Pharmaceuticals’ antibody cocktail, which Trump touted as a “cure.” Trump has previously promoted Eli Lilly’s treatments as well as others.
Interestingly on October 8, Regeneron applied
to the U.S. Food and Drug Administration (FDA) for Emergency Use Authorization (EUA) for its antibody cocktail. Around the same day, Eli Lilly reported it had submitted its EUA request for a EUA for LY-COV555 as a monotherapy to the FDA. At that time, it said it believed it could supply up to 100,000 doses by the end of October and up to 1 million by next year.
Industry speculators said that Eli was trying to get fast regulatory approval in order to dump its stockpile of monotherapy antibodies it had manufactured as it knew that they might not be effective in the long term due to antibody strains emerging and becoming prevalent.
Lilly stated, at that time, “We expect to submit a subsequent request for EUA for combination therapy in November, pending the clinical trial enrollment, once additional safety data accumulate, and sufficient supply is manufactured.”
It is not yet clear if yesterday’s ACTIV-3 pause will affect either the initial EUA application or the timeline for the subsequent combination EUA request.
Thailand Medical News will be providing more updates as we expect more vaccine and antibody trials to be stopped in the next few weeks.
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