By Marisa Taylor and Robin Respaut
(Reuters) - As the United States accelerates the search for a coronavirus vaccine, tensions have erupted between government scientists and Moderna Inc, one of the leading developers, Reuters has learned.
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.
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.
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.
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)