Chloroquine Researcher Oversaw Trial for Drug That Sparked Rare Prosecution

(CN) — Five days after President Donald Trump touted hydroxychloroquine as a game-changer in the fight against Covid-19, the Department of Health and Human Services awarded PPD Development a $750,000 contract to develop a treatment protocol for expanded access to the antimalaria drug.

A North Carolina-based researcher, PPD for most does not have the same name recognition associated with Sanofi, the French pharmaceutical giant that manufactures a branded form of hydroxychloroquine. Some two decades ago though, its oversight of a Sanofi-Aventis drug clinical trial tied it forever to one of the industry’s rare prosecutions.

An arrangement of hydroxychloroquine pills, photographed Monday in Las Vegas. (AP Photo/John Locher)

Sparking criminal prosecution, nationwide litigation and a congressional hearing, study 3014 of an antibiotic called Ketek put doctor Marie Anne Kirkman Campbell in prison for fraud. Campbell served 57 months after pleading guilty to having fabricated documentation supporting the existence of a fictitious subject. 

The FDA ultimately approved Ketek in April 2004, despite Campbell’s plea one month earlier, but the drug was largely pulled from the shelves three years later after it was linked to dozens of cases of liver failure.

“Our investigation found that Dr. Kirkman Campbell’s site did not adequately address these issues and that Aventis and PPD did not adequately follow up to explain the data discrepancies,” the FDA wrote in its 2007 warning letter to Sanofi-Aventis.

Earlier that year, PPD’s research associate Ann Marie Cisneros told the congressional committee investigating it: “What brings me here today is my disbelief at Aventis’s statements that it did not know that fraud was being committed.”

“Mr. chairman, I knew it,” Cisneros emphasized. “PPD knew it, and Aventis knew it.”

The Courthouse News database shows at least seven lawsuits against Sanofi and PPD in connection with the Ketek study. PPD did not respond to a request for comment.

President Donald Trump speaks about the coronavirus at the White House on Monday. (AP Photo/Alex Brandon)

Some 17 years after Campbell’s conviction, PPD now stands tasked with expanding access to the drug hoped to treat, and possibly even prevent, Covid-19, the deadly respiratory disease caused by a new coronavirus.

Trump, who has an indirect and fairly small financial stake in Sanofi, has been touting the promise of hydroxychloroquine since the first briefing of his White House coronavirus task force.

“I have to say, if chloroquine or hydroxychloroquine works — or any of the other things that they’re looking at that are not quite as far out — but if they work, your numbers are going to come down very rapidly,” the president speculated on March 19, as infections and deaths continued to surge across the country.

PPD’s contract began five days after that briefing. It has an anticipated end date of April 21.

Sanofi only sells its branded version of hydroxychloroquine outside of the United States, following a 2013 divestment deal.

“We were not made aware of President Trump’s announcement on Plaquenil (hydroxychloroquine) as a potential treatment for COVID-19,” Sanofi spokesman Nicolas Kressman said. “We heard about it in real time along with the American public.”

In the U.S., the marketing and sale of Plaquenil is done by Advanz, formerly known as Concordia, a Swiss company that owned Covis Pharma. Sanofi on Friday offered 100 million doses of Plaquenil to governments worldwide if studies show it can be safely used to treat Covid-19 patients.

Following his enthusiastic endorsement of hydroxychloroquine on March 19, Trump has falsely claimed in multiple briefings and on Twitter that the FDA approved its use against the novel coronavirus and that the drug cannot hurt patients.

“There is no U.S. Food and Drug Administration approved product available to treat Covid-19,” the agency emphasized on a fact sheet for patients receiving that treatment under its emergency authorization. 

Research has ramped up worldwide to fortify the hopes for the drug with sound science. At press time, the U.S. clinical trials database shows 61 studies into various uses of hydroxychloroquine for use against Covid-19. Of these 21 have been taking place in the United States.

One study underway at Rutgers University’s Robert Wood Johnson University Hospital has an estimated enrollment of 160 participants and is scheduled to last a year.

Dr. Steven Libutti, a surgical oncologist and director of Rutgers Cancer Institute of New Jersey, disclosed that patients so far have tolerated the drug, which is already approved for lupus and arthritis.

“With respect to our trial we have not seen any worrisome adverse reactions at this point,” Libutti said in an email. “We won’t have any information about efficacy until we complete the study.”

The Rutgers study is nearly six times the size of the French one that Trump amplified in a tweet, which had a sample of 26 patients who took hydroxychloroquine and azithromycin, a common antibiotic.

“HYDROXYCHLOROQUINE & AZITHROMYCIN, taken together, have a real chance to be one of the biggest game changers in the history of medicine,” Trump wrote on March 21, attributing the claim to the International Journal of Antimicrobial Agents. “The FDA has moved mountains.” 

Residents of the Malawi village of Tomali wait to have their young children become test subjects for the world’s first vaccine against malaria on Dec. 11, 2019. (AP Photo/Jerome Delay)

But the board that publishes that journal backtracked from its claims on April 3, saying the study did not meet its expected standards. Six subjects dropped out of that study, but it gained traction after Tesla’s CEO Elon Musk tweeted the paper, which became a talk of conservative media before catching the attention of the White House. 

The randomized study at Rutgers investigates the same drug combination in more detail, with one experimental arm taking the two medications in combination, one taking hydroxychloroquine alone, and a third with no intervention.

“I believe our study is better powered to detect a difference if there is one,” Libutti said, comparing the university’s study with the French one. 

In a regular refrain during his press briefings, Trump has taken to asking those interested in taking chloroquines for the prevention or treatment of Covid-19: “What do you have to lose?”

Dr. Dena Grayson, a physician who helped research an antiviral drug to combat the deadly Ebola disease, gave a stark answer.

“This drug that can cause fatal heart arrhythmias, meaning an abnormal heartbeat where people can literally drop dead,” Grayson said in a phone interview of hydroxychloroquine.

On Wednesday, the American Heart Association issued guidance in its flagship medical journal Circulation, where it warned about the combination of hydroxychloroquine and azithromycin for patients with cardiovascular disease.

“The urgency of Covid-19 must not diminish the scientific rigor with which we approach Covid-19 treatment,” the association’s president Robert Harrington wrote in a statement.

Grayson noted that the drug combination Trump endorsed can exacerbate this issue.

“So, it is extremely reckless, and I want to just emphasize that you have somebody who has no medical training whatsoever out there touting a very unproven potential treatment,” Grayson said.

New York Governor Andrew Cuomo noted that some of the anecdotal reports on the drug’s potential against the virus have been promising, but he emphasized that an official study would take weeks if not months longer to complete.

Grayson, who has developed drugs for more than 15 years, stressed that doctors who run clinical studies take their obligations to protect the safety and privacy of their patients seriously, and she had never heard of a case of a criminal prosecution for defrauding such research. 

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Editor’s note:

After this article was published, a spokeswoman for the Department of Health and Human Services emphasized that PPD’s contract is not for a clinical trial. 

“As a clinical research organization, PPD is under contract to collect and analyze data related to the outcomes of patients who received doses of these drugs donated to the Strategic National Stockpile and sent to states for use in treating hospitalized Covid-19 patients under EUA,” the spokeswoman said, referring to the FDA’s emergency use authorization for the drug. “This data collection is a condition of the FDA’s Emergency Use Authorization (EUA) for these donated drugs and will inform continued availability under the EUA. All information collected through this outcomes data collection will be reviewed by BARDA and, as appropriate, by FDA.”

Short for Biomedical Advanced Research and Development Authority, BARDA is the subsection of the agency responsible for protecting the United States from chemical, biological, radiological and nuclear threats. “PPD is one of five CROs in BARDA’s Clinical Studies Network, created in 2014,” the spokeswoman continued. “PPD has been successful in the past working directly with BARDA or as part of a team supporting BARDA’s industry partners on BARDA-supported development programs.”

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