Vaccines are still on the frontline for Covid-19 prevention, but an experimental AstraZeneca drug is posting clinical data showing that it could offer an additional measure. The pharmaceutical giant now has results from a pivotal Phase 3 study showing that its antibody drug succeeded in reducing Covid infections by 77%.
With those results in hand, AstraZeneca said Friday that it will prepare regulatory submissions for emergency authorization or conditional approval of the drug, AZD7442, in Covid-19 prevention.
Vaccines prompt the immune system to produce antibodies that protect against infection. A prophylactic antibody drug is intended to give patients the antibodies that their body doesn’t produce from vaccination. Antibody drugs have been developed for treatment of Covid-19 infection, including FDA authorized drugs from Regeneron Pharmaceuticals, Eli Lilly, and Vir Biotechnology. AstraZeneca is also developing AZD7442 as a Covid-19 treatment. But the clinical trial results reported Friday support using the drug to help patients that need something in addition to vaccines to help prevent infection in the first place.
The Phase 3, placebo-controlled study, called PROVENT, enrolled 5,197 adults spanning 97 sites in the U.S., United Kingdom, Spain, France, and Belgium. These participants were adults who were predicted to be poor responders to vaccines or were otherwise intolerant of them. The study also included those whose circumstances put them at a higher risk of exposure to the virus. According to the company, more than 75% of study participants had underlying conditions associated with a reduced immune response to vaccination. The main goal of the clinical trial was to measure cases of Covid-19 infection, confirmed by PCR testing, occurring after dosing until day 183 of the study.
AstraZeneca said the trial yielded 25 cases of symptomatic Covid-19 at the primary analysis point. No cases of severe disease or Covid-related deaths were reported in those who received AZD7442. In the group given the placebo, three cases of severe Covid-19 were reported, including two deaths. The AstraZeneca antibody combo was well tolerated by patients and the company said that preliminary analyses show adverse events were balanced between the placebo and treatment groups. Participants in the study will continue to be followed for 15 months.
AZD7442 is a combination of two long-acting antibodies, tixagevimab and cilgavimab. Both antibodies were derived from B-cells donated by convalescent patients who were infected by SARS-CoV-2. AstraZeneca licensed the antibodies last year from Vanderbilt University Medical Center, where they were discovered. These antibodies bind to different sites of the novel coronavirus, an approach intended to increase efficacy and reduce the chances that a viral mutation will render the drug ineffective.
Though antibody drugs currently available for Covid-19 treatment are also in development for preventing SARS-COV-2 infection, AstraZeneca’s drug could offer two advantages. Unlike currently authorized antibody drugs administered as intravenous infusions, AZD7442 is a more patient-friendly intramuscular injection (though Vir and Regeneron are also developing injectable versions of their antibody drugs). AstraZeneca also designed AZD7442 to provide its protective benefit for longer. AstraZeneca applied a proprietary technology to the Vanderbilt antibodies that extends their half-lives, making them last for as long as 12 months. Furthermore, the drug is optimized to reduce binding to Fc receptors, which AstraZeneca said minimizes the risk that virus-specific antibodies promote rather than inhibit infection and disease.
“The PROVENT data show that one dose of AZD7442, delivered in a convenient intramuscular form, can quickly and effectively prevent symptomatic COVID-19,” Myron Levin, professor of pediatrics and medicine at the University of Colorado School of Medicine and the principal investigator of the clinical trial, said in a prepared statement. “With these exciting results, AZD7442 could be an important tool in our arsenal to help people who may need more than a vaccine to return to their normal lives.”
In addition to the clinical trial data in Covid-19 prevention, AstraZeneca said preliminary lab test results from Oxford University and Columbia University show that the drug neutralizes variants of SARS-CoV-2, including the delta strain. AstraZeneca said it will submit full results from the PROVENT clinical trial for publication in a peer-reviewed medical journal; they will also be presented at an upcoming medical meeting.
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