Colossal Wrongdoings by Big Pharma – Servier – Asrar Qureshi’s Blog Post #1094

Colossal Wrongdoings by Big Pharma – Servier – Asrar Qureshi’s Blog Post #1094

Dear Colleagues! This is Asrar Qureshi’s Blog Post #1094 for Pharma Veterans. Pharma Veterans Blogs are published by Asrar Qureshi on its dedicated site https://pharmaveterans.com. Please email to pharmaveterans2017@gmail.com  for publishing your contributions here.

Credit: Andres Ayrton

Credit: Annushka Ahuja

Credit: Artem Podrez

Preamble

For decades, benfluorex – sold under the brand name ‘Mediator’, was marketed as a diabetes and weight-loss drug by French pharmaceutical giant Servier Laboratories. Hailed as a useful tool to help overweight patients manage their health, Mediator was widely prescribed in France and a few other countries from the mid-1970s until 2009. But beneath its therapeutic promise lurked a dangerous reality: the drug was linked to serious, and often fatal, heart valve problems and pulmonary hypertension.

By the time it was pulled off the market, Mediator was estimated to have caused between 500 and 2,000 deaths in France alone. The scandal rocked the French healthcare system, raised global concerns about pharmaceutical oversight, and led to one of the most high-profile court cases in French medical history.

The Drug and Its Intended Use

Benfluorex was developed in the 1970s by Servier, one of France’s largest privately owned pharmaceutical firms. The drug was approved for use primarily as an adjunct treatment for overweight patients with Type 2 diabetes, helping control blood sugar and promote weight loss.

However, in practice, Mediator was widely prescribed off-label for weight loss — including to people who were neither diabetic nor clinically obese. With an estimated five million people exposed to the drug in France alone, it became one of the most frequently prescribed appetite suppressants in the country.

A Sister Compound with a Deadly History

Benfluorex belongs to a class of drugs known as fenfluramines, which are chemically similar to another notorious weight-loss drug: fen-phen (fenfluramine/phentermine). Fen-phen was banned in the United States in 1997 due to its association with serious heart valve damage and pulmonary arterial hypertension.

Despite the growing scientific consensus that benfluorex metabolizes into norfenfluramine — the same active metabolite that caused fenfluramine’s toxicity — Servier insisted that Mediator was a different drug, claiming it was safe and effective for its intended use. But internal reports and mounting evidence suggested otherwise.

Early Warnings Ignored

Red flags began appearing as early as the late 1990s and early 2000s, when several cardiologists began reporting cases of unexplained heart valve disease in patients who had taken Mediator. A French drug safety agency, AFSSAPS, began collecting adverse event data but failed to act decisively.

In fact, internal memos and reports, which came to light during later investigations, indicated that Servier was aware of the risks associated with Mediator long before it was withdrawn. Yet the company continued to market the drug aggressively and resisted regulatory scrutiny.

One of the most damning pieces of evidence was that benfluorex had been withdrawn from the markets in Spain and Italy in the early 2000s over safety concerns — yet it continued to be prescribed in France for nearly a decade more.

The Whistleblower

The scandal might have remained buried had it not been for Dr. Irène Frachon, a pulmonologist at the Brest University Hospital in Brittany. In 2007, she noticed an unusual cluster of patients suffering from valvulopathies — diseases affecting the heart valves — who had all taken Mediator.

Dr. Frachon began a personal investigation, collecting data, working with epidemiologists, and eventually publishing a book in 2010 titled "Mediator 150 mg: How Many Deaths?" Her work, though initially met with resistance from the medical establishment and legal threats from Servier, became a national rallying point.

Following her findings, a government-commissioned epidemiological study confirmed that Mediator significantly increased the risk of heart valve disease and pulmonary hypertension, estimating hundreds — possibly thousands — of deaths.

The Withdrawal and Legal Firestorm

In November 2009, under mounting pressure, AFSSAPS finally withdrew Mediator from the French market. But the damage had already been done.

In 2010, French authorities opened a criminal investigation into Servier, charging the company with "aggravated deception," "manslaughter," and "unintentional injuries". The charges included not just marketing a dangerous drug but also deliberately misleading regulators and doctors about its risks.

After more than a decade of legal wrangling, the landmark verdict came in March 2021. The Paris court found Servier guilty of deceit and manslaughter, fining the company €2.7 million (only). Several executives received suspended prison sentences. The court also criticized the French drug regulatory system for “failing in its mission to safeguard public health.”

Systemic Regulatory Failure

One of the most painful lessons from the Mediator case was the systemic failure of drug regulation in France. Despite numerous warnings from doctors, internal agency reports, and evidence from other countries, Mediator remained on the market for decades.

Critics argued that the French regulator, AFSSAPS, had a too-cozy relationship with pharmaceutical companies, and failed to act independently in the public interest. The scandal prompted major reforms in France’s drug safety system, including:

• Replacing AFSSAPS with a new independent body, ANSM (Agence nationale de sécurité du médicament).

• Strengthening conflict-of-interest rules for regulators and doctors.

• Mandating greater transparency in post-marketing drug surveillance.

• Creating a victim compensation fund for those affected by Mediator.

Servier’s Reputation and Damage Control

For Servier, the fallout from the Mediator scandal was enormous. Although the company was fined, critics pointed out that €2.7 million was a small penalty for a firm with billions in revenue. However, the reputational damage was incalculable.

Servier defended itself by claiming that it had acted in good faith and had never intended to harm patients. However, the court documents and investigative reports painted a different picture — one of deliberate obfuscation and negligence.

Key Lessons Learned

Though Mediator was mostly prescribed in France, the scandal had global ramifications. It spurred debate across Europe and other parts of the world about how drugs are regulated, how adverse events are monitored, and how much influence pharmaceutical companies have over healthcare policy.

Key lessons from the Mediator scandal include:

1. Transparency in drug approval and monitoring is essential.

2. Whistleblowers are critical allies in ensuring public safety.

3. Regulators must maintain independence from industry interests.

4. Off-label use of medications must be tightly controlled and evaluated.

5. Public health systems must have robust mechanisms for post-market surveillance.

Sum Up

The Mediator scandal serves as a tragic reminder of what happens when commercial interests supersede patient safety. It is a story of systemic failure, corporate malfeasance, and courageous advocacy by individuals like Dr. Frachon.

Thousands suffered — and many died — because a dangerous drug remained on the market long after evidence of its harm was available. While regulatory reforms in France and the broader EU followed in its wake, the scandal remains a haunting chapter in the history of pharmaceutical ethics.

In an era of complex healthcare systems and global supply chains, the Mediator case underscores a universal truth: public trust in medicine must be earned through transparency, accountability, and an unwavering commitment to patient welfare.

Concluded.

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