(Reuters) — Newly unsealed court documents and other records show that Merck & Co and U.S. regulators knew about reports of suicidal behavior in men taking the company’s anti-baldness treatment Propecia when they decided not to warn consumers of those potential risks in a 2011 update of the popular drug’s label.

Internal records from Merck were made public in late January, when a federal magistrate in Brooklyn, New York, granted a 2019 Reuters motion to unseal 11 documents filed in years of litigation alleging Propecia caused persistent sexual dysfunction and other harmful side effects.

Since the 2011 decision on the warning, the FDA has received more than 700 reports of suicide and suicidal thoughts among people taking Propecia or generic versions of the drug. Those included at least 100 deaths. Before that, in the first 14 years the drug was on the market, the agency received 34 such reports, including 10 deaths.

Annual U.S. prescriptions of finasteride, as the drug is known, for hair loss increased to over 2.4 million in 2020, more than double the number in 2015, according to health data company IQVIA.

European and Canadian regulators, citing similar reports among men taking finasteride, require a warning of suicidal thoughts on the label, though they note that research has not proved that the drug causes such thoughts. To this day, the U.S. label contains no mention of suicide or suicidal thoughts.

As early as 2009, Merck knew of more than 200 reports of depression, including suicidal thoughts, in men taking Propecia, according to an internal “risk management” assessment from that year. The company decided there were too few reports of serious depression and suicidal behavior and not enough specifics about those cases to warrant more than “routine” monitoring of safety data.

In 2011, two years after the Merck risk analysis, the FDA was weighing a company request to add “depression” to the drug’s label as a potential risk, with no warnings related to suicide. FDA analysts disagreed about adding a warning related to suicide, according to previously unreported government documents. But the regulator ultimately agreed with Merck’s request on the grounds that the number of suicides was lower than one would expect in this group of patients.

CALLS FOR TRANSPARENCY

Some medical researchers and patient advocates said Merck and the FDA have left American consumers in the dark about potentially life-threatening dangers associated with finasteride.

“No family should ever have to learn about this after the fact,” said Kim Witczak, a consumer advocate who serves on an FDA advisory panel for psychiatric drugs. She has called for drug companies and regulators to issue stronger warnings after her husband died from suicide in 2003 five weeks after being prescribed an antidepressant for insomnia. Merck “had an opportunity to put suicide on the label, but they didn’t want to do that because it’s all about sales.”

Michael Irwig, an endocrinologist and Harvard Medical School faculty member whose own research has found possible links between finasteride and suicidal behaviors, said Merck’s handling of the risk analysis and the FDA’s inaction keep critical information from the public. Merck “definitely should have provided a more complete picture,” Irwig said.

In a statement to Reuters, Merck said that “the scientific evidence does not support a causal link between Propecia and suicide or suicidal ideation and these terms should not be included in the labeling” for the drug. “Merck works continuously with regulators to ensure that potential safety signals are carefully analyzed and, if appropriate, included in the label for Propecia.”

Merck has said in past statements that Propecia has been prescribed safely to millions of men since the late 1990s. It also has argued in court that “premature hair loss itself, the very condition for which Propecia is prescribed, is associated with low self-esteem, poor body image, and depression.”

In a statement, FDA said it “continues to monitor postmarketing safety data for Propecia.” Overall, the agency noted that the presence of a report in the FDA database “does not mean the drug caused the adverse event” and medical problems may stem from the “underlying disease being treated, caused by some other drug being taken concurrently, or occurred for other reasons.”

FDA declined to comment further about its handling of Propecia and reports related to suicide.

Merck’s analysis of a potential suicide risk stayed secret in court for over three years — and only became public after Reuters intervened in the proceeding. The insights in the recently unsealed documents echo findings from Reuters’ 2019 investigation, “Hidden Injustice,” which revealed how U.S. judges routinely allow makers of consumer products to file under seal in lawsuits information that is pertinent to public health and safety. They often do so without explanation, though in most jurisdictions, they are required to provide one.

The Reuters investigation found that hundreds of thousands of Americans have been killed or seriously injured in recent decades by allegedly defective products — including drugs, cars and medical devices — while evidence that could have alerted consumers and regulators to potential danger remained hidden.

In granting Reuters’ motion to unseal Merck documents, U.S. Magistrate Judge Peggy Kuo last month ruled that the company’s arguments for continued secrecy “are so weak that they would not overcome even a low presumption of access under the common law.”

INTERNAL DIFFERENCES

In addition to the risk management plan, Kuo unsealed other Merck documents including an internal marketing report from prior to the drug’s launch and some communications with regulators regarding sexual dysfunction. Reuters obtained the FDA documents discussing suicide from a separate online repository maintained by the agency.

In 2010, while reviewing Merck’s proposal to add potential depression risk to Propecia’s label, an FDA safety evaluator recommended also adding a warning for suicidal thoughts and behavior, noting nine suicides and reports of other suicidal behaviors among patients who took finasteride, the FDA documents reviewed by Reuters show.

The reports of suicidal behavior analyzed by Merck and government regulators, known as “adverse event” reports, are filed by consumers, doctors and other members of the public. They are compiled in a public database by U.S. regulators, as well as drug-safety agencies in other countries.

In her November 2010 report, FDA safety evaluator Namita Kothary wrote that the nine suicides were difficult to assess due to incomplete information. “However, we cannot exclude that finasteride may have contributed to the events,” she wrote. Kothary did not respond to requests for comment.

Two other FDA reviewers disagreed. The two physicians — Amy Woitach and David Kettl — said the data supported adding depression to the label. Suicidal ideation, however, should be left off because the number of suicidal thoughts, attempts and deaths was “lower than would be expected in this patient population,” according to their December 2010 report. Kettl and Woitach did not respond to requests for comment.

The European Medicines Agency found the relationship between finasteride and depression was hard to assess, but still required a warning about suicidal ideation in 2017, in part because Propecia is not prescribed for a serious condition, according to EMA committee meeting minutes. Doctors and patients generally weigh risks differently for a drug to treat a life-threatening health problem, versus something less severe.

When Health Canada required its warning in 2019, it noted 368 international reports of suicidal events reported in patients treated with finasteride through September 2018. Merck did not respond to questions about these regulatory moves.

The FDA approved Propecia in 1997, and sales climbed steadily through the 2000s, peaking at $447 million in 2010. Soon after, Merck’s patent expired. Overall sales of finasteride have remained strong as cheaper generic versions have hit the market.

PERSISTENT DYSFUNCTION

The new information regarding a potential suicide risk emerged as a result of longstanding controversy about sexual problems associated with the drugs.

From the beginning, Merck’s label said Propecia caused sexual dysfunction in nearly 4% of its clinical study participants. However, the 2009 risk management report also shows that the company was aware of reports that those sexual problems continued for some men after they stopped taking the drug.

The FDA in 2012 approved Merck’s request to add a warning of erectile dysfunction that continued after stopping the drug, as well as “libido disorders, ejaculation disorders, and orgasm disorders.” Even so, Merck at the time said scientific evidence did not establish that Propecia caused persistent sexual dysfunction.

The warning prompted more than 1,100 lawsuits against Merck by men alleging their sexual problems lasted long after they stopped taking Propecia. Merck in 2018 agreed to settle most of the lawsuits consolidated before Judge Brian Cogan in Brooklyn federal court for a combined $4.3 million.

Reuters reported in 2019 that prior to the settlement, plaintiffs’ lawyers had alleged that Merck, when revising the drug’s original label, understated the number of men who experienced sexual symptoms in clinical trials and how long those symptoms lasted. The allegation was part of a sealed court brief a Reuters reporter was able to read because of a redaction error. The brief cited internal Merck communications, filed under seal. Reuters intervened in the case, seeking to unseal those communications.

“IMPORTANT POTENTIAL RISK”

The 2009 risk management report unsealed last month shows that while depression did not emerge as a risk in clinical trials, Merck deemed it an “important potential risk” after the company received 218 global reports of depression from 1998 to 2008. Of those, 10 involved serious depression, and an additional nine involved suicidal behavior.

Merck noted limitations with both the depression reports and the nine involving suicidal behavior. Four provided “insufficient information to allow a full evaluation.” Three of the men had other medical conditions, and for two, the symptoms developed after they stopped taking the drug.

“One fatal report was received from a sheriff’s office and described a male who committed suicide by shooting,” according to the report. “The medical examiner did not think this event was related to Propecia, in addition, the report provided insufficient information to allow for assessment.”

The report contained no additional details about the patient’s identity or the medical examiner’s investigation. Merck did not respond to questions about what steps it took to learn more about the case.

In its statement to Reuters, Merck said adverse event reports reflect only the opinions of the person who files them. “While consumers and healthcare professionals are encouraged to report adverse events, the reaction may have been related to the underlying disease being treated, or caused by some other drug being taken concurrently, or occurred for other reasons,” the company said.

Dr. W. Vaughn McCall, chairman of the Department of Psychiatry and Health Behavior at the Medical College of Georgia, agreed that relying on adverse event reports to monitor drug safety has its limitations. However, he said one of those limitations is that injuries and deaths are often underreported because people aren’t familiar with the process or don’t have time to examine a specific case.

He said there is a plausible biological explanation for a potential link between Propecia and suicidal thoughts. The drug reduces a testosterone-related hormone, which in turn could impact an anti-depressive steroid produced in the body.

“There is a reason to be suspicious,” McCall said.

(Reporting by Dan Levine in San Francisco and Chad Terhune in Los Angeles. Editing by Janet Roberts and John Blanton.)

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