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 The federal government is supporting Moderna’s vaccine project with
nearly half a billion dollars and has chosen it as one of the first
to enter large-scale human trials.
But the company - which has never produced an approved vaccine or
run a large trial - has squabbled with government scientists over
the process, delayed delivering trial protocols and resisted
experts’ advice on how to run the study, according to three sources
familiar with the vaccine project. The sources said those tensions,
which have not been previously reported, have contributed to a delay
of more than two weeks in launching the trial of the Moderna’s
vaccine candidate, now expected in late July.
Moderna “could be on schedule if they were more cooperative,” one of
the sources told Reuters.
Some of the disagreements have stoked concerns over the young
biotech firm’s relative inexperience and what the sources described
as its lack of staff and expertise to oversee the most critical
phase of human trials. The U.S. government is not facing similar
problems with established drugmakers, such as AstraZeneca Plc and
Johnson & Johnson, working on other leading vaccine candidates, the
sources said.
Moderna and other vaccine developers are working with the U.S.
National Institutes of Health (NIH) and the Food and Drug
Administration (FDA), along with networks of immunologists and other
vaccine experts tasked by the NIH to help oversee trial design.
Moderna denied any missteps on its part but acknowledged
“differences of opinion” with experts involved in the unprecedented
effort to deliver on the Trump administration’s pledge to find a
vaccine within months. It typically takes about a decade to develop
a vaccine - and many efforts fail to produce one at all. Moderna
said it has an experienced team that includes people who have run
multiple large-scale trials.
“It has not been smooth or easy,” said Moderna spokesman Ray Jordan.
“No one has ever done anything like this before - not Moderna, not
the NIH, and not any of the other companies.”
In one disagreement, Moderna executives resisted experts’ insistence
on close monitoring of trial participants who might contract
COVID-19 for changes in oxygen levels that could signal dangerous
complications. While other drugmakers complied, Moderna questioned
the recommendation as a “hassle” that slowed development, one of the
sources told Reuters. Jordan said the company preferred to defer all
decisions about monitoring to patients’ physicians but that the
company ultimately agreed to some monitoring.
Despite a bumpy process, Moderna remains ahead of other firms in the
race for a vaccine, according to statements from the government and
the companies. The firm, founded a decade ago, has outpaced much
larger companies despite the steeper challenges Moderna faces in
scaling up staff and capacity to create a vaccine at breakneck
speed. AstraZeneca and Johnson and Johnson are also steaming toward
their own large-scale trials, but they are behind Moderna in the
United States.
Stephen Thomas, a vaccine developer who is chief of infectious
diseases at SUNY Upstate Medical University, said vaccine
development can spark such disagreements even without the pressures
of an out-of-control pandemic.
“Those tensions, in and of themselves, don't indicate that Moderna
is incapable of doing it,” Thomas said.
In a statement to Reuters, the U.S. Health and Human Services
Department (HHS) said the government’s collaboration with Moderna,
as with all organizations in the project, has been “extremely
cooperative.” The agency said Moderna’s vaccine candidate is the
most advanced and has shown excellent performance in early trials.
HHS declined to respond to further questions. NIH and the FDA
declined to comment.
‘WARP SPEED’
The Trump administration’s “Operation Warp Speed” vaccine program is
run by HHS in partnership with other agencies. It is led by Moncef
Slaoui, a former GlaxoSmithKline executive who more recently served
on Moderna’s board of directors. He stepped down in May to run the
government’s COVID-19 vaccine project.
Moderna’s vaccine technology uses genetic material called messenger
RNA to instruct human cells to produce coronavirus proteins that
prompt an immune response. The firm was picked early by NIH because
of its technology’s potential to accelerate development. Moderna
developed a vaccine candidate in about two months, making it the
first to move to early human testing in a small U.S. trial of
healthy volunteers in March.
The NIH had hoped to launch Moderna’s large-scale trial by July 10
but the disputes with the company caused the delay, the sources
said. Medical news site STAT first reported the trial delay on
Thursday.
The company attributed the delay to the need to accommodate
last-minute compromises with the NIH and to allow the government to
coordinate trials with multiple drugmakers. Moderna’s Jordan called
its interactions with government experts a healthy scientific
debate. “There have, of course, been differences of opinion, but we
believe there has always been good intent,” he said.
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Moderna and other vaccine developers have been given significant control and
responsibility over the large-scale, so-called Phase 3 trials by HHS. But
Moderna has been less forthcoming than other drugmakers about its plans, the
sources said.
Moderna outsourced the handling of data collection to the contract research firm
PPD Inc. At one meeting set up with the leading companies and government
officials, Moderna did not allow PPD to share details of the trial plans, as
other companies had done, the sources said. PPD did not respond to request for
comment.
Moderna disputed that it withheld information, calling the complaint a
misunderstanding about the company’s presentation at the meeting, which was not
as detailed as others.
Moderna delayed submitting its clinical trial protocols by several weeks, the
sources said. The protocols lay out goals and detailed procedures for
researchers to manage the trial safely. While Moderna maintained it made the
call to delay the trial launch, the sources said Moderna lacked enough staff to
complete the protocols on time.
Moderna also initially sought a lower threshold for proving whether its vaccine
worked than what was ultimately set by the FDA, one of the sources said. The
company says it has aligned with the FDA’s guidance after discussions with the
agency.
One of the sources said such disputes and delays speak to a larger problem in
the government’s interactions with Moderna. “They try to test every boundary,”
the person said.
HIGH STAKES
The stakes could not be higher for the Trump administration. More than 130,000
Americans have died in the pandemic, and the urgency for a vaccine is growing as
coronavirus infection rates rise in 39 states.
HHS awarded Moderna $483 million in April to accelerate vaccine development and
manufacturing. The company says it is already gearing up to produce at least 100
million doses this year to ensure supply even before trials prove its vaccine
safe and effective.
For Moderna, managing its first large-scale vaccine trial is a critical test of
its ability to deliver to the public and investors. Moderna has about 20
potential vaccines and therapies in its pipeline, but none are near regulatory
approval. Before its pursuit of a COVID-19 vaccine, the company’s largest
clinical trial involved about 250 participants, according to the federal
government’s database of clinical trials. The large-scale trial for its COVID-19
vaccine will have 30,000 test subjects.
The Cambridge, Mass.-based firm has long been a darling of biotech investors,
and its chief executive, Stéphane Bancel, is a master fundraiser. In 2018 the
company broke records for launching the industry’s largest initial public
offering, valued at $7.5 billion. Moderna’s market capitalization has grown to
about $23 billion in recent months amid hopes for its coronavirus vaccine.
Both Bancel and Chief Medical Officer Tal Zaks have pocketed tens of millions of
dollars since the start of the year by selling shares that have tripled in price
on news of Moderna’s development progress, Reuters reported last week. The sales
have amounted to $21 million for Bancel and over $35 million for Zaks, who has
cashed out the majority of his available stock and options. (For full story
click https://reut.rs/38yKm7z )
In May, the company announced that its candidate had appeared safe and produced
protective antibodies in a small subset of the healthy volunteers in the first
clinical trial. The announcement - which boosted Moderna’s stock by 20% - drew
criticism from some scientists who wanted to see the full data. The study
results are expected to be published in the New England Journal of Medicine.
In response, Moderna has said that the company worked “cooperatively” with NIH
to properly characterize the early data.
Bancel has consistently cast the company’s messenger RNA technology - which he
calls the “software of life” - as a breakthrough in both the speed and
effectiveness of vaccine development. “We are not aware of anybody else who can
do this at this scale, with this focus, at this speed,” he told investors in
June. Bancel has said that the company could have the data to prove its
vaccine’s effectiveness by November.
“The Moderna CEO has been very brash about his company’s technology,” said Peter
Pitts, former FDA associate commissioner from 2002 to 2004 and now president of
the Center for Medicine in the Public Interest, a New York-based research and
educational organization. In vaccine development, he said, “often the higher the
boasting, the lower the chance of actual success.”
Such overconfidence, Pitts said, can damage public health by signaling that
strict precautions, such as social distancing and mask-wearing, may not be as
necessary. “If you give the impression that the problem is solved, it’s
dangerous,” he said. “People think the vaccine is just around the corner.”
Moderna’s Jordan said the company invites the comparison of its public
statements with its results.
“Our statements about the future potential of our platform must be held up
against the clinical data as it emerges,” Jordan said. “We believe that, to
date, they have.”
(Reporting by Marisa Taylor and Robin Respaut; Editing by Michele Gershberg and
Brian Thevenot)
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