Tag Archives: FDA

Biogen Alzheimer’s drug closer to approval with U.S. FDA staff backing, shares jump 40%

By Deena Beasley and Manojna Maddipatla

(Reuters) – Biogen Inc has shown “exceptionally persuasive” evidence that its experimental Alzheimer’s disease drug is effective, U.S. Food and Drug Administration staff said on Wednesday, elevating its chances of a swift approval and sending company shares soaring.

An FDA approval could come by March, which would make the drug, aducanumab, the first new treatment for the disease in decades and the first that appears to be able to slow progression of the fatal, mind-wasting condition that affects millions of people.

Shares of Biogen and its partner Eisai Co Ltd both jumped 40%. The FDA staff comments also buoyed shares of other Alzheimer’s drug developers, including a 15% rise in shares of Eli Lily and Co.

The agency’s documents were released ahead of a meeting on Friday of outside experts who will review, and decide whether to recommend approval of, aducanumab, an antibody designed to remove amyloid plaques from the brain.

“Briefing documents suggests a positive Advisory Committee vote, which bodes well for approval,” Guggenheim analyst Yatin Suneja said in a research note. Mizuho Securities analyst Salim Syed called it “almost a best-case scenario” for Biogen.

FDA drug reviewers said results from one pivotal trial of aducanumab were persuasive and strongly positive. They acknowledged that a second large trial did not succeed, but maintained it did not detract from the findings of the positive study. The FDA is not obligated to abide by its expert panel recommendations, but typically does.

One statistical reviewer at the FDA said another study is needed to confirm whether aducanumab is effective. “There is no compelling substantial evidence of treatment effect or disease slowing,” FDA staffer Tristan Massie wrote in the review.

Alzheimer’s disease afflicts nearly 6 million Americans and millions more worldwide. Biogen estimates about 1.5 million people with early Alzheimer’s in the United States could be candidates for its drug.

Patient advocacy groups have argued that aducanumab needs to be approved due to that large unmet medical need.

“If a third trial is recommended then years could go by … while people aren’t granted access to the drug,” said Dr. Howard Fillit, chief science officer at the Alzheimer’s Drug Discovery Foundation.

Biogen and its investors also need an aducanumab approval after the company recently lost a patent fight over its big-selling multiple sclerosis drug Tecfidera. If approved, annual sales are forecast to reach $5.3 billion by 2025, according to Refinitiv.

Cambridge, Massachusetts-based Biogen in October last year revived its plans to seek approval for aducanumab, months after it had said that an independent futility analysis of its two pivotal studies showed they were unlikely to succeed.

Biogen said it changed course after a new analysis showed a high dose of the drug could slow disease progression.

The FDA staff said data from one of the trials “provides the primary evidence of effectiveness as a robust and exceptionally persuasive study demonstrating” a clinically meaningful treatment effect.

Shares of Biogen were up $99.57 at $346.58, and shares of Eisai were up $30.82 at $110.12.

(Additional reporting by Manas Mishra in Bengaluru; Editing by Shinjini Ganguli and Bill Berkrot)

Q&A: Where are we in the COVID-19 vaccine race?

By Carl O’Donnell

NEW YORK (Reuters) – Drugmakers and research centers around the world are working on COVID-19 vaccines, with large global trials of several of the candidates involving tens of thousands of participants well underway.

As some companies close in on unveiling their initial findings – with Canadian and European regulators already reviewing early data on some vaccines – the following is what we know about the race to deliver vaccines to help end the coronavirus pandemic that has claimed over a million lives:

Who is furthest along?

U.S. drugmaker Pfizer Inc with German partner BioNTech SE, U.S. biotech Moderna Inc and Britain-based AstraZeneca Plc in conjunction with University of Oxford researchers could provide early analyses of data from their various large trials as early as October or November. Johnson & Johnson is a bit further behind.

What happens in these trials?

The companies are testing their vaccines against a placebo – typically saline solution – in healthy volunteers to see if the rate of COVID-19 infection among those who got the vaccine is significantly lower than in those who received the dummy shot. Neither trial participants nor researchers know who has received the vaccine or placebo until the data is ready for review, or unblinded. The studies rely on subjects becoming naturally infected with COVID-19, so how long it takes to generate results largely depends on how pervasive the virus is where the trials are being conducted. In areas with large outbreaks and community spread, infections will pile up faster.

How will we know if the vaccine works?

The United States, the European Union, the United Kingdom and the World Health Organization have all set similar minimum standards for effectiveness. Vaccines must demonstrate at least 50% efficacy – meaning at least twice as many infections among volunteers who got a placebo as among those in the vaccine group. Independent panels oversee the trials to monitor for safety and effectiveness since the data is hidden from companies and researchers. These data safety monitoring boards take a peek at the interim results at pre-determined milestones, such as after a certain number of people have become infected. If the vaccine is looking significantly better than the placebo, the companies can apply for emergency use, and the study may be halted or continue to its intended conclusion. A trial can also be halted if the panel determines the vaccine to be unsafe.

Will regulators ensure a vaccine is safe before making it available to the public?

The U.S. Food and Drug Administration has said it will not approve a vaccine unless it is both effective and safe. Earlier this month, it added more stringent safety guidelines for U.S. vaccines. The FDA wants developers to follow trial subjects for at least two months after they receive their final vaccine dose to check for any side effects that may crop up. The agency will consider an emergency use authorization (EUA) once that data is collected from at least half of the trial’s participants. The UK Medicines and Healthcare products Regulatory Agency will review the vaccines for the UK and the European Medicines Agency will review vaccines for European Union use.

When will regulators decide?

Regulators will review the vaccines after the companies have enough data to submit applications seeking an EUA or formal approval. Moderna’s first look at data is more likely to come next month. AstraZeneca could provide a look at late-stage data in November. Pfizer/BioNtech said it may have data as early as October, but that it would wait for safety data it expects in the third week of November to file with U.S. regulators.

Regulators for Europe and Canada are considering data on a rolling basis, as it becomes available. The UK and the United States both expect speedy reviews of initial data for possible emergency use before more traditional lengthy reviews for formal commercial approvals.

Could these be the first approved coronavirus vaccines?

Yes, although China and Russia are on a similar timeline. China launched an emergency use program in July aimed at essential workers and others at high risk of infection that has vaccinated hundreds of thousands of people. At least four vaccines are far along including from China National Biotec Group [CHNAPF.UL] (CNBG), CanSino Biologics <6185.HK> and Sinovac. Sinovac and CNBG have said to expect early trial data as soon as November. Russia’s Gamaleya Institute has begun a 40,000-person late-stage trial and is expected to have early data at the end of October or early November. Russia has also given the vaccine to at least hundreds of “high-risk” members of the general population.

Is U.S. authorization up to President Trump?

The FDA must make sure that the benefits of a vaccine outweigh the risks before authorization since they are intended to be given to hundreds of millions of healthy people. However, the U.S. Department of Health and Human Services (HHS) has the authority to override the FDA’s recommendation. President Donald Trump has complained about the new safety guidelines, which delay any vaccine availability until after the Nov. 3 presidential election at the earliest. The Trump administration can hire and fire HHS officials, opening the possibility of political pressure to approve a vaccine.

(Reporting by Carl O’Donnell in New York; Additional reporting by Julie Steenhuysen in Chicago, Michael Erman in New York, Ludwig Burger in Frankfurt, Alistair Smout in London and Polina Ivanovo in Moscow; Editing by Caroline Humer, Bill Berkrot and Frances Kerry)

Pfizer says earliest COVID-19 vaccine application to U.S. regulators would be after election

By Manas Mishra and Michael Erman

(Reuters) – Pfizer Inc said on Friday it may file for U.S. authorization of the COVID-19 vaccine it is developing with German partner BioNTech in late November, making it unlikely a vaccine will be available before the U.S. election as President Donald Trump has promised.

Pfizer said that it may say if the vaccine is effective as soon as this month based on its 40,000 person clinical trial but that it also needs safety data that will not be available until November at the earliest.

The Pfizer news, published in a letter from its chief executive on its website, lifted the U.S. stock market and the company’s shares. Shares were up slightly in rival vaccine maker Moderna Inc, which is close to Pfizer in its vaccine development.

“So let me be clear, assuming positive data, Pfizer will apply for Emergency Authorization Use in the U.S. soon after the safety milestone is achieved in the third week of November,” Pfizer Chief Executive Albert Bourla said.

Trump has said repeatedly that there would be a vaccine available before the election, but health officials and companies had only said that data might be available this month. The possibility of further delays was raised after trials for two rival vaccines were put on hold in the United States this fall.

The president’s rush to a vaccine has also raised concerns that the U.S. Food and Drug Administration, acting in haste, might not conduct an adequate review of the vaccine.

U.S. health officials have sought to assuage those concerns out of fear that not enough Americans would take a vaccine early on. Earlier this month, the FDA formalized a requirement that the vaccine makers collect two months of safety data on one-half of trial participants.

Pfizer’s comments on its time line raise the possibility of U.S. authorization of a coronavirus vaccine this year, a key step in controlling the COVID-19 pandemic, which has killed more than a million people and ravaged the global economy.

Moderna could also apply for an emergency use authorization (EUA) this year. It has said that it may have interim data on its 30,000 person trial as soon as November.

Both companies are also applying for approval in Europe, where they are racing against AstraZeneca PLC. AstraZeneca’s U.S. trial has been on hold since September.

After the FDA announced the two-month requirement on Oct. 6, which was approved by the White House but undercut the likelihood of a vaccine before voters go to polls on Nov. 3., Trump called the move a ‘political hit job.’

In addition to safety and efficacy, the FDA will also examine Pfizer’s manufacturing operations for the vaccine.

Bourla said the filing depended on several other factors, including initial data on effectiveness that may or may not be available by late October.

He said the company plans to share efficacy data with the public as soon as practical. (https://bit.ly/31bWdpP)

A BioNTech spokeswoman confirmed the time frame for the possible EUA application to the FDA.

Pfizer’s shares rose 2.1% in premarket trading, while BioNTech’s U.S-listed shares were up 4% before the opening bell. Moderna was unchanged and U.S. futures were higher.

(Reporting by Manas Mishra, Manojna Maddipatla in Bengaluru and Michael Erman in New Jersey, Patricia Weiss in Frankfurt; writing by Caroline Humer in New York; Editing by Patrick Graham, Saumyadeb Chakrabarty and Steve Orlofsky)

NIH starts clinical trial testing antibody treatments in COVID-19 patients

(Reuters) – The U.S. National Institutes of Health (NIH) said on Tuesday it has started a study to evaluate two antibody treatments in COVID-19 patients as part of the agency’s program to identify promising drugs to help tackle the new coronavirus.

The trial will test AbbVie Inc’s psoriasis drug risankizumab along with Gilead Sciences’ antiviral remdesivir, compared to a placebo and remdesivir.

The study will also test Humanigen’s experimental drug lenzilumab with remdesivir, compared to placebo and remdesivir.

“The goal here is to identify as quickly as possible the experimental therapeutics that demonstrate the most clinical promise as COVID-19 treatments and move them into larger-scale testing,” said NIAID Director and U.S. infectious diseases expert Anthony Fauci.

Gilead’s remdesivir, which was among the first to be used to treat COVID-19 and received emergency use authorization from the U.S. Food and Drug Administration in May, has since been authorized for use in several other countries.

Risankizumab and lenzilumab belong to a class of drugs known as monoclonal antibodies that are laboratory-made versions of proteins naturally produced by the immune system in response to invading viruses or other pathogens.

The treatment has come under the spotlight after U.S. President Donald Trump was treated with Regeneron Pharmaceuticals’ antibody drug earlier this month.

Regeneron and Eli Lilly have both applied to the U.S. FDA for emergency use of their antibody treatments.

(Reporting by Amruta Khandekar; editing by Ankur Banerjee and Ramakrishnan M.)

Abbott wins U.S. emergency use authorization for new COVID-19 antibody test

(Reuters) – Abbott Laboratories said on Monday the U.S. Food and Drug Administration has issued an emergency use authorization for its lab-based COVID-19 antibody blood test.

The test, AdviseDx, can be used to identify a type of antibody called Immunoglobulin M (IgM) in blood samples to determine if someone has been exposure to the novel coronavirus, potentially indicating a recent or prior infection.

Abbott has already received emergency use authorization for seven tests, including molecular tests, a rapid antigen test and another test which can detect a type of antibody called IgG.

The FDA’s emergency use authorization allows the use of unapproved medical products in an emergency to diagnose, treat, or prevent serious or life-threatening diseases with no adequate or approved alternatives.

IgG is longer lasting in the body after an infection, but IgM is more useful for determining a recent exposure to the coronavirus as these antibodies become undetectable weeks to months following an infection, Abbott said.

Unlike molecular tests, which can detect whether someone has the coronavirus, antibody tests determine if someone has had a previous infection by detecting disease-fighting proteins called antibodies.

However, antibody tests are not recommended as the sole basis of diagnosis of COVID-19 as these antibodies may not be detected in the early days of the infection.

Shares of Abbott were up 0.5% at $110.21 in early trading.

(Reporting by Manojna Maddipatla in Bengaluru; Editing by Amy Caren Daniel)

Most Americans to be vaccinated for COVID-19 by July, CDC chief expects

(Reuters) – A top U.S. health official told a U.S. Senate committee on Wednesday that he expects COVID-19 vaccinations to take place over many months and that most Americans could be vaccinated by July of 2021 at the latest.

U.S. Centers for Disease Control and Prevention head Robert Redfield said he expects there to be about 700 million doses of vaccines available by late March or April, enough for 350 million people.

“I think that’s going to take us April, May, June, you know, possibly July, to get the entire American public completely vaccinated,” Redfield told the U.S. Senate Health, Education, Labor and Pensions Committee.

Redfield, U.S. Food and Drug Administration head Stephen Hahn, U.S. National Institute of Allergy and Infectious Diseases head Anthony Fauci and Health and Human Services official Brett Giroir were testifying on the COVID-19 pandemic, which has caused more than 200,000 deaths in the United States.

There is no vaccine for COVID-19 yet, but there are several in late stage trials here, including from Pfizer Inc., Moderna Inc. and Johnson & Johnson. Companies have begun manufacturing the vaccine in anticipation of a fast regulatory authorization once they are shown to work.

Fauci said he expects 50 million doses to be available in November and 100 million by the end of December. He expects a total of 700 million doses by April.

Health officials and President Donald Trump have presented different views about when the vaccines will be ready for most Americans. The process for deciding how to distribute vaccines falls largely to the CDC.

Redfield said Operation Warp Speed, the government group with officials from the departments of Health and Human Services and Defense, will ultimately decide how to allocate the vaccines.

PLAYING DEFENSE

Senator Patty Murray, the highest ranking Democrat on the committee, pointed to some reported examples of Trump administration pressure on the health agencies, including FDA authorizations of hydroxychloroquine and convalescent plasma as treatments for COVID-19 and changes in the CDC’s guidance on testing for asymptomatic individuals.

“Any of these examples of political pressure would be alarming on their own. But together they paint a clear pattern of interference that is downright terrifying,” she said.

Redfield and Hahn defended their agencies against criticism of their handling of the pandemic, telling the committee they were using science as their guide, not politics.

“FDA will not authorize, or approve, a vaccine that we would not feel comfortable giving to our families,” Hahn said.

Redfield said the agency’s change to guidance for testing for asymptomatic individuals with close contact to a COVID-19 positive person was poorly written. It has since been updated to make it clear that such individuals should get a test, he said.

The CDC will release new guidance on the role of aerosolized coronavirus in its spread, Redfield said. The agency took down a Sept. 18 update to its transmission guidance that mentioned airborne virus for the first time, as it lacked the needed technical review.

Redfield also said that based on an antibody testing study, about 90 percent of Americans are still vulnerable to the virus.

(Reporting by Michael Erman and Manas Mishra in Bengalaru; Writing by Caroline Humer; Editing by Chizu Nomiyama, Bernadette Baum and Howard Goller)

Moderna would seek limited emergency use of COVID-19 vaccine based on early data

By Julie Steenhuysen

CHICAGO (Reuters) – If Moderna Inc’s COVID-19 vaccine proves to be at least 70 percent effective, the company plans to seek emergency authorization for its use in high-risk groups, the company’s chief executive told Reuters.

Moderna’s vaccine candidate – mRNA-1273 – is nearing the finish line in its push to enroll 30,000 individuals in a late-stage trial of a novel coronavirus vaccine. But the company may be able to declare victory early if it is able to show that people who got the vaccine fared much better in its trial that people who didn’t.

Vaccines must demonstrate they are at least 50% more effective than a placebo to be considered for approval. To prove that, government officials have said, at least 150 COVID-19 infections must be recorded among trial participants with at least twice as many occurring among the placebo group.

If a vaccine is especially effective, companies could have their answer sooner.

An independent safety board will take a first look at Moderna’s data as soon as a total of 53 people in the trial become infected with COVID-19. Moderna is projecting the interim analysis will occur in November, but it could come as early as October.

If most of the people who got sick got the placebo shot, that would indicate the vaccine was protecting those inoculated and could be enough evidence to seek U.S. regulatory approval for Emergency Use Authorization (EUA).

“If the interim readout is deemed by the independent safety committee as positive with 70 or 80 or 90% efficacy, we will indeed consider approval,” Stephane Bancel, Moderna’s chief executive officer, said in a telephone interview.

“At such a level of efficacy, if we get there, we can protect a lot of lives in the people at the highest risk, and so, we will consider filing for an EUA for a very limited population,” Bancel said.

He said the FDA will determine whether the benefit of the vaccine to a small group of high-risk individuals outweighs the risk of not having a full readout of safety data from all 30,000 study participants.

The two groups of high-risk individuals who might be covered in such an EUA would be healthcare workers and the elderly, Bancel said.

Bancel said the company wants to gather more data on the safety of the vaccine in the study population over a period of several months before seeking full FDA approval.

Moderna released its study protocol on Thursday, making public details on how its vaccine will be evaluated. If the vaccine does not reach the efficacy mark after 53 cases, the data safety and monitoring board will take another interim look at the data after 106 cases, and a final look after 151 people in the trial become infected with the virus.

Public health officials have said that approving a vaccine for widespread use based on a small number of cases would not offer enough safety information to show how the vaccine would perform.

Moderna, which has never brought a vaccine to market, has received nearly $1 billion from the U.S. government under its Operation Warp Speed program. It has also struck a $1.5 billion supply agreement with the United States.

In a presentation to investors on Tuesday, Pfizer Inc said the company has enrolled more than 29,000 people in its 44,000-volunteer trial to test an experimental COVID-19 vaccine the company is developing with German partner BioNTech.

Pfizer expects to have enough data to show whether the vaccine works by the end of October.

(Reporting by Julie Steenhuysen; editing by Peter Henderson and Cynthia Osterman)

Exclusive: AstraZeneca COVID-19 vaccine trial in U.S. on hold until at least midweek – sources

By Julie Steenhuysen and Marisa Taylor

CHICAGO (Reuters) – AstraZeneca’s COVID-19 vaccine trial remains on hold in the United States pending a U.S. investigation into a serious side effect in Britain even as other trials of the vaccine resume, sources familiar with the details told Reuters.

AstraZeneca on Saturday said it had restarted its trial in Britain after regulators completed their review of a serious side effect in one trial participant there.

This was the first indication that the U.S. trial will remain on hold until the U.S. Food and Drug Administration and a safety panel investigate the case.

Enrollment in the company’s global trials of the vaccine, which it is developing with researchers at Oxford University, was put on pause on Sept. 6.

Sources told Reuters that enrollment of new patients and other trial procedures for the pivotal U.S. trial were being rescheduled until at least midweek and that it was not clear how long it would take for the FDA to complete its probe.

Governments around the world are desperate for a vaccine to help end the pandemic, which has caused more than 900,000 deaths and global economic turmoil. The World Health Organization (WHO) had flagged AstraZeneca’s as the most promising. A prolonged delay in the U.S. trial could slow access to the vaccine in the United States.

The British adverse event involved a study patient thought to be suffering a rare spinal inflammatory disorder called transverse myelitis.

An AstraZeneca spokeswoman declined to comment on when the U.S. trial would resume. She said in an email the company “will continue to work with health authorities across the world, including the FDA, and be guided as to when other clinical trials can resume.”

The status of the South African and Indian trials remains unknown, but the trial in Brazil has also restarted. The company has not commented on timing of resumption in other parts of the world besides Britain.

FDA did not immediately respond to a request for comment.

(Reporting by Julie Steenhuysen and Marisa Taylor; Editing by Peter Henderson and Cynthia Osterman)

Exclusive: U.S. hospitals turn down remdesivir supplies, limit use to sickest COVID-19 patients

By Deena Beasley

(Reuters) – U.S. hospitals have turned down about a third of their allocated supplies of the COVID-19 drug remdesivir since July as need for the costly antiviral wanes, according to unpublished government statistics provided to Reuters by a U.S. pharmacists’ group.

Some hospitals said they are still buying the Gilead Sciences medicine to build inventory in case the pandemic accelerates over the winter. But they said current supplies are adequate, in part because they are limiting use to severely ill patients.

The Food and Drug Administration has allowed more liberal remdesivir use, but 6 out of 8 major hospital systems contacted by Reuters said they were not using it for moderate cases.

The slowdown suggests that a shortage of the drug is over and threatens Gilead’s efforts to expand use of remdesivir, which it sells under the brand name Veklury in some countries.

The U.S. Department of Health and Human Services (HHS) told hospitals and other healthcare organizations on Friday that between July 6 and September 8, state and territory public health systems accepted about 72% of the remdesivir they were offered, Michael Ganio, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists, told Reuters.

Hospitals in turn took only about two-thirds of what states and territories accepted, he added. It was not immediately clear what happened to the surplus supplies.

Neither Gilead nor HHS immediately responded to requests for comment.

A surplus of remdesivir – which costs $3,120 for a 6-vial intravenous course – marks a turnaround from earlier in the pandemic, when supplies of the drug had fallen short of demand in some regions.

Government-led distribution of remdesivir will expire at the end of September. Hospitals said they have little information on availability after that.

Remdesivir was first authorized by the FDA in May for emergency use in COVID-19 patients hospitalized and on oxygen support after data showed that it helped shorten hospital recovery time.

The agency last month expanded use to hospitalized patients who do not require oxygen support, based on data published in the JAMA medical journal showing that the drug provided a modest benefit for those patients.

The newer data has left many experts unconvinced.

Dr. Aneesh Mehta, chief of infectious diseases services at Atlanta’s Emory University Hospital, said Emory is focusing supplies on patients likely to benefit the most.

“I am not terribly impressed with the study,” said Dr. Adarsh Bhimraj, an infectious disease specialist at the Cleveland Clinic. He said he remains “skeptical” about using remdesivir in patients with moderate COVID, especially given the price.

(Reporting By Deena Beasley; editing by Peter Henderson and Bill Berkrot)

U.S., European COVID vaccine developers pledge to uphold testing rigor

By Ludwig Burger, Patricia Weiss and Caroline Copley

FRANKFURT (Reuters) – Nine leading U.S. and European vaccine developers pledged on Tuesday to uphold the scientific standards their experimental immunizations will be held against in the global race to contain the coronavirus pandemic.

The companies, including Pfizer, GlaxoSmithKline and AstraZeneca, issued what they called a “historic pledge” after a rise in concern that safety and efficacy standards might slip in the rush to find a vaccine.

The companies said in a statement they would “uphold the integrity of the scientific process as they work towards potential global regulatory filings and approvals of the first COVID-19 vaccines”.

The other signatories were Johnson & Johnson, Merck & Co., Moderna, Novavax, Sanofi and BioNTech.

The promise to play by established rules underlines a highly politicized debate over what action is needed to rein in COVID-19 quickly and to jump start global business and trade.

The head of the U.S. Food and Drug Administration (FDA) said last month COVID-19 vaccines may not necessarily need to complete Phase Three clinical trials – large-scale testing intended to demonstrate safety and efficacy – as long as officials are convinced the benefits outweigh the risks.

This prompted a call for caution from the World Health Organization (WHO).

Developers globally have yet to produce large-scale trial data showing actual infections in participants, yet Russia granted approval to a COVID-19 vaccine last month, prompting some Western experts to criticize a lack of testing.

The head of China’s Sinovac Biotech has said most of its employees and their families have already taken an experimental vaccine developed by the Chinese firm under the country’s emergency-use program.

Chinese companies or institutions, which are involved in several leading vaccine projects, did not sign the statement.

PROMISE ON SAFETY AND EFFICACY

“We want it to be known that also in the current situation we are not willing to compromise safety and efficacy,” said co-signatory Ugur Sahin, chief executive of Pfizer’s German partner BioNTech.

“Apart from the pressure and the hope for a vaccine to be available as fast as possible, there is also a lot of uncertainty among people that some development steps may be omitted here.”

BioNTech and Pfizer could unveil pivotal trial data as early as October, potentially placing them at the center of bitter U.S. politics before the Nov. 3 presidential election.

President Donald Trump has said it is possible the United States will have a vaccine before the election. His Democratic rival, Kamala Harris, has said she would not take his word alone on any potential coronavirus vaccine.

The nine companies said they would follow established guidance from expert regulatory authorities such as the FDA.

Among other hurdles, approval must be based on large, diverse clinical trials with comparative groups that do not receive the vaccine in question. Participants and those working on the trial must not know which group they belong to, according to the pledge.

BioNTech’s Sahin said there must be statistical certainty of 95%, in some cases higher, and that a positive reading on efficacy does not come just from random variations but reflects the underlying workings of the compound.

The development race has intensified safety concerns about an inoculation, polls have shown.

Western regulators have said they would not cut corners but rather prioritize the review workload and allow for development steps in parallel that would normally be handled consecutively.

Sahin declined to comment on regulators specifically or on what events prompted the joint statement.

The chief executive of German vaccine developer Leukocare, which did not sign the pledge, was more forthright.

“What Russia did – and maybe also there are tendencies in the U.S. to push the approval of a vaccine which has not been sufficiently developed in clinic – bears a huge risk,” said CEO Michael Scholl.

“My biggest fear is that we will approve vaccines that are not safe and that will have a negative impact on the concept of vaccinations in general.”

Leukocare is working with Italy’s ReiThera and Belgium’s Univercells to produce a COVID-19 vaccine currently in phase I testing.

(Reporting by Ludwig Burger, Patricia Weiss in Frankfurt and Caroline Copley in Berlin; Editing by Susan Fenton and Timothy Heritage)