Moderna Inc. dosed the first of what could be as many as 30,000 healthy volunteers Monday morning as it began its phase III COVID-19 vaccine trial. Those volunteers at increased risk of contracting COVID-19, with a large percentage being elderly or people with co-morbidities – those most at risk for life-threatening COVID-19 infections – will receive placebo or Moderna’s vaccine candidate, mRNA-1273.

Tal Zaks, Moderna’s chief medical officer, told investors in a July 15 conference call that Moderna is working closely with its Operation Warp Speed colleagues and the U.S. NIH, including the National Institute of Allergy and Infectious Disease's COVID-19 Prevention Trials Network, to achieve the shared goal that trial participants represent both communities at highest COVID-19 risk and the country’s diverse makeup.

Tal Zaks, chief medical officer, Moderna

The company said Monday the research sites were chosen with “representative demography” that would ensure volunteers at increased risk are enrolled. The sites also are said by Moderna to work with local communities to “reach a diverse” population.

In July 21 testimony before the U.S. House Energy and Commerce Committee’s subcommittee on oversight and investigations, Stephen Hoge, Moderna’s president, noted “that communities of color and the working class have disproportionately borne the burdens of COVID-19.”

“We've approached this challenge really at two levels,” Zaks said during the earlier call. “First, picking vaccination – vaccinating centers and experts in areas of current and anticipated exposure to infection. Think of this as figuring out what the right ZIP code to go after or to go to. And second, working with the local investigators and communities in those ZIP codes so that we can enable those who are at highest risk for both infection and disease to have the opportunity to enroll.”

Zaks said the trial design takes into account the belief that older people are the more vulnerable population. There will be “a significant portion of the trial that is going to be people who are either older or have co-morbid conditions such that we can ensure that we're not just bringing an effective vaccine to those who are more likely to get infected,” he said. “We're also making sure that we understand the safety and efficacy in those who are more likely to get sick should they get infected.”

The phase III trial’s biggest risk, Zaks said, is the attack rate in the peak of the population that will get vaccinated. Moderna should be able to vaccinate people, who, some ultimately by chance and disposition, are going to be at risk and will end up being exposed to the virus, he added.

“To the degree that we are unable to capture those individuals and we end up vaccinating people who do not get exposed, I think it will be very hard to make a determination,” he said. “We'll have a great safety database, but it will make it challenging to demonstrate efficacy. So I see that as the greatest risk right now.”

The clinical trial, whose protocol has been reviewed by the FDA and is tied to its clinical trial design for COVID-19 vaccine studies, is created to evaluate mRNA-1273’s efficacy, safety and immunogenicity in preventing COVID-19 for up to two years after a second dose of mRNA-1273. The nearly 100-site, U.S.-based, randomized study’s primary outcome measures include the number of participants with a first occurrence of COVID-19 starting 14 days after the second dose. The time frame is from the second dose to two years afterward. Another primary outcome measure is the number of participants with adverse events or medically attended adverse events up to two years after the second dose.

Secondary endpoints include the number of participants with a first occurrence of severe COVID-19, defined as hospitalization, starting 14 days after the second dose and the number of participants with a first occurrence of either COVID-19 or SARS-CoV-2 infection regardless of symptomatology or severity starting 14 days after the second dose.

Participants, ages 18 and older, will receive either placebo or one intramuscular injection of 100 mcg of mRNA on day one and then again 28 days later.

“The data will be reviewed on an ongoing basis by an independent safety monitoring committee led by NIH, and this trial is expected to have two interim analyses at approximately 53 and 106 events prior to the final event-driven analysis at approximately 151 events,” Zaks said.

Top-line data may be available by late 2020.

Piper Sandler analysts wrote Monday that recently published interim phase I data for healthy subjects receiving mRNA-1273 in The New England Journal of Medicine demonstrated generation of neutralizing antibody titers of two- to fourfold above convalescent serum from COVID-19 survivors and showed T-cell response.

“We believe these data showed clean safety and robust immunogenicity to support the selected phase III 100-μg mRNA-1273 dose,” the analysts added.

Moderna said it remains on track to be able to deliver about 500 million doses annually and possibly up to 1 billion doses per year beginning in 2021.

Deciding who gets the vaccine first is yet to be determined. That’s a decision to be made by the federal government and local governments, according to Stéphane Bancel, Moderna’s CEO. He said people who need the vaccine most should get it first, saying elderly people with co-morbidity factors should receive it before young people with no co-morbidities. Who gets it, however, is not a decision for a private company to make, he said.

“So we could see, in the case of the U.S., potentially working hand in hand with the CDC, where we will ship from our filling facilities finished product to different depot centers across the country for the U.S., where then they will do allocations to hospitals or pharmacies and/or schools over locations that they will decide to do the deployment,” Bancel said.

More BARDA funding comes Moderna’s way

As a boost, the U.S. Biomedical Advanced Research and Development Authority (BARDA) gave 10-year-old Moderna up to $472 million to support the study and mRNA-1273’s late-stage development. That’s in addition to the $483 million it received from BARDA in April to scale up the vaccine and its clinical development. The increase comes in the wake of decisions made in the past few months to enlarge the phase III design, which had originally envisioned a smaller number of participants. The funding now totals about $955 million.

Moderna’s dispute with Arbutus

A July 23 decision by the U.S. Patent Trial and Appeal Board rejected Moderna’s request to invalidate U.S. Patent 8,058,069 held by Arbutus Biopharma Inc., of Vancouver, British Columbia, which relate to lipid formulations for nucleic acid delivery. In their decision, the judges determined Moderna has not “shown by a preponderance of the evidence” that claims relating to the patent are unpatentable. On Monday, Moderna responded by saying the continued development of technology and manufacturing have advanced beyond what is described in the legacy Arbutus patents. The technology, which is used to manufacture mRNA-1273, is not covered by the Arbutus patents, Moderna added, and added that it is not aware of any significant intellectual property impediments for products it intends to commercialize, including mRNA-1273.

H.C. Wainwright and Co. analysts wrote Monday that they “cannot be certain at this juncture of the ultimate outcome of this dispute, or whether it is likely to result in any settlement between Moderna and Arbutus. However, developments in this case may have implications not only for Moderna's COVID-19 vaccine but also for its platform as a whole.”

Cambridge, Mass.-Moderna’s stock (NASDAQ:MRNA) closed 9.15% upward on Monday, with shares selling at $79.91.

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