Sanofi: Lemtrada Drug (2013)

Controversy

Sanofi Company logo

In December of 2013, the FDA denied the MS (Multiple Sclerosis) drug, C, from being marketed. The denial was due to the impractical Phase III clinical trial setup and how the benefits failed to outweigh the side effects. It was stated that “Lemtrada would have to demonstrate substantial clinical benefits, the FDA noted, or the drugs ‘serious and potentially fatal safety issues’ would scuttle the marketing application” (Carroll 1 - UPDATED). The clinical trials were at fault in this case; the experiments were the reason why the drug was denied the first time. The article, Sanofi’s Lemtrada Wins U.S. Approval to Treat MS states that “Genzyme shareholders who won publicly traded contingent value rights stood to receive payments of as much as $14 a share by the end of 2020 if Sanofi met certain goals, most of them tied to the approval and sale of Lemtrada” (Bloomberg 2). This $14 a share dropped to approximately $0.25 due to the setback of Lemtrada being introduced into the market. Sanofi released their decision to try and regain the FDA’s approval a second time in late 2013.

Lemtrada, the drug denied for MS by the FDA

The FDA is a challenging organization to appeal towards. However, Sanofi engaged in efforts to try and change the panel’s minds. The FDA wanted Sanofi to conduct “one or more additional active comparator clinical trials of different design and execution” in order for Lemtrada to be approved (Carroll 2 – UPDATED). Viehbacher did not plan on fully fulfilling the FDA’s request. Sanofi rolls the dice again on Lemtrada after an FDA rejection states that Sanofi did not lose hope on Lemtrada, and instead of performing one or more clinical trials as suggested by the FDA, the company used “a new analysis of the same data” in hopes that it would “sway regulators in a second review” (Garde 1). Another one of Carroll’s articles, Sanofi’s MS team rebuilds its case for the FDA rejected MS drug Lemtrada, Sanofi reported that “during the third year of follow-up in their extension study, more than 70% of patients were free of MRI activity indicative of acute inflammation, defined as gd-enhancing or new or enlarging T2 hyperintense lesions” (Carroll 2). Yes, this is a positive outcome reported from the extension study, but two deaths also resulted from the study: “one from sepsis and another that was deemed accidental and unrelated” (Carroll 2 – Sanofi’s). Tracy Staton, author of the article Sanofi misled investors with rosy Lemtrada predictions, lawsuit alleges, wrote that after the denial, some investment funds sued Sanofi. On March 28th, 2014, a lawsuit was filed in the New York federal court by investment funds, claiming that Genzyme and Sanofi were releasing information about their confidence in Lemtrada receiving approval ‘“without disclosing that their communications from the FDA were telling them the contrary”’ (Staton 1). As of April 7th, 2014, Sanofi failed to respond to the complaint. The lawsuit also stated that “Genzyme said in a Securities & Exchange Commission filing that management were 90% certain that Lemtrada would win FDA approval by March 31st” of 2014 (Staton 2). The defendants in the lawsuit were the company and three top executives. On May 30th, 2014, it was revealed that Sanofi’s supplemental application was accepted “thus kicking off a 6-month review period with a final decision expected in the fourth quarter” of 2014 (Garde 1). In November of 2014, the FDA approved the drug, but limited who could use it.

Stakeholders

Chris Viehbacher, former CEO of Sanofi

The stakeholders in this case are Sanofi, Genzyme, the FDA, competitors, investors, leukemia victims, MS patients, and the healthcare community. The investment that Sanofi made in the drug Lemtrada was originally estimated to have peak sales of approximately $700 million. The FDA denial caused the $700 million estimation to “drop considerably as analysts assess the damage” (Carroll 1 - UPDATED). This drop in profit, at first, must have affected investors because they most likely did not receive their share of income, and expectations of success were not met. Even though the drug was accepted by the FDA, there still was a financial loss and an emotional toll of those who spent copious amounts of time on the development of the drug. Competitors, such as Bigoen Idec and Novartis were able to make a larger contribution to the market. Investors could have lost trust in the pharmaceutical company. Leukemia patients were left with one less drug as an option, which negatively can impact their health if the drug was economically efficient and an appropriate use for treatment. MS patients were forced to wait a longer period of time before being able to consume the drug.

Multiple Sclerosis effects on the nerves/myelin sheath

Individualism

Individualists would deem this case unethical. Individualism signifies the company’s responsibility to provide profits solely for their owner. Laws must be abided by when businesses turn their decisions into actions. According to Heather Salazar’s The Case Manuel, Individualism follows values pertaining to “the business, the owner’s choices, and business profits” (Salazar 17). The overall goal of a pharmaceutical business is to find success through the drug development and approval processes in order to sell the drug in the marketplace. The Phase III clinical trials were not performed within the quality and safety standards of the FDA. When a pharmaceutical company is involved in a clinical trial, not only do they need to follow Constitutional law, but they must follow the rules and regulations of the Food and Drug Administration. Failure to do this will result in the denial of a drug and a profit loss: the result of the FDA’s first response to Lemtrada. Business profits plummeted, which caused anger from investors who had high hopes for the approval of the MS drug. Individualists also produce as much money for the stockholders as possible. A lawsuit filed against Sanofi “says the ‘defendant’s fraud’ amounted to tens of millions of dollars of investor losses” (Staton 1). At first, Sanofi failed to maximize profits for the business, which in turn did not maximize profits for investors. Instead, they were accused of committing an illegal business action, fraud.

Utilitarianism
According to utilitarianism, happiness must be achieved in the long run for all stakeholders involved in the business action. A long-term outcome of this could have been that the appeal did not work. In December of 2013, Carroll revealed in his first article that “appeals related to the FDA are generally futile, leaving Sanofi staring at a major new investment for a drug that is unlikely to carve out a very large place for itself in the MS market” (Carroll 1 - UPDATED). The FDA acts as a high authoritative figure in the pharmaceutical business, so it seems odd that the drug would be denied and the accepted in a span of about one year. The initial denial “left a mark on the company’s R&D rep that wasn’t helped by the flurry of lawsuits that followed from angry investors who claimed to have been duped by the pharma giant” (Carroll 1 – Sanofi’s). People outside of the company who supported them were not happy. During the time period of this case, “rival drug maker Biogen Idec has launched its new MS treatment Tecfidera” (Staton 2). Sanofi’s delay from the primary denial of Lemtrada must have caused frustration and impatience due to wasted time and profit loss. Another long-term effect of Lemtrada on patients who participated in the three year extension study consisted of “T2 lesion volumes—the combined burden of permanent brain injury and new lesion formation” which “did increase from year two to three but remained below pretreatment baseline” (Carroll 2 – Sanofi’s). The study resulted in two deaths, one from sepsis and the other was reported to not be related to the study. Lives were lost and there were prevalent negative side effects from taking Lemtrada. This case would be deemed unethical.

Kantianism

U.S. FDA logo

Kantian theorists would view this case as unethical. Lying, cheating, manipulating, or harming others in order to please the business are all unethical according to Kantianism. Kantianism seeks to “always act in ways that respect and honor individuals and their choices” (Salazar 20). Morality and appropriate motivation of business actions are two substantial factors of this theory. Sanofi’s motivation in this ethical case was driven by profit. The company failed to treat their patients as an end, but rather as a means to test the effectiveness of Lemtrada. Sanofi rolls the dice again on Lemtrada after an FDA rejection says that Sanofi gambled “that a new analysis of the same data will sway regulators in a second review” (Garde 1). The formulation of humanity “states that it is wrong to use people as a mere means to get what you want” (Salazar 22). Sanofi possibly could have thought that they were exempt from some of FDA’s rules or had the ability to work around them while conducting their clinical trials. Failure to act rationally led to primary failure in the drug approval process.

Virtue Theory

Virtue theory highlights the ability to “act so as to embody a variety of virtuous or good character traits and so as to avoid vicious or bad character traits” (Salazar 22). Sanofi failed to show honesty, one of the four principles of Virtue Theory. Sanofi and Genzyme told their investors the opposite of what the FDA thought about the drug. The primary denial also was unfair to those MS patients who could have used the drug sooner than later. There was no justice involved in the clinical trials of the drug due to unfair practices and a poor quality drug being the result. Virtue theorists would agree that this case is unethical.

Justified Ethics Evaluation

In my opinion, the denial of Lemtrada the first time resulted from poor management. Failure always reaches management because they are the leaders of any company, and they also decide the disciplinary rules, codes, and morals of the company. Genzyme’s failure to carry out the Phase III clinical trials correctly the first time portrayed Sanofi’s failure to lead their subsidiary to successful results. It is obvious that the wrong people worked for the company because the clinical trials were not carried out under FDA guidelines, which resulted in a waste of time and profit; in the end the CEO of Sanofi was fired. Even though the drug was accepted by the FDA, the warnings on the box still seem severe, and who knows if MS patients will consume the product due to the past controversy. Pharmaceutical companies need to focus more on the patient rather than the profit. Yes, I know that pharmaceutical companies are businesses, and need to make profit in order to run the business, pay for wages, and produce more successful drugs. However, it seems that profit-oriented companies face more of a loss than a gain due to lack of leadership and preparation. I believe that Sanofi’s dishonesty with the media about their confidence in the drug was wrong. They should have been honest, because then they would uphold at least a better reputation than they might now hold. I also think that it was wrong of Sanofi to not perform one or more additional clinical trials to prove the efficacy of the drug because it shows that the company is not dedicated to the successful results in the patients.

References

Bennett, Simeon, and Anna Edney. "Sanofi's Lemtrada Wins U.S. Approval to Treat MS."
Bloomberg.com. Bloomberg, 15 Nov. 2014. Web. 21 Oct. 2015.

Carroll, John. "FDA Reverses an Embarrassing Rejection of Sanofi's Lemtrada, OKs MS Drug." FierceBiotech. FierceBiotech, 15 Nov. 2014. Web. 21 Oct. 2015.

Carroll, John. "Sanofi's MS Team Rebuilds Its Case for the FDA-rejected MS Drug
Lemtrada." FierceBiotech. FierceBiotech, 30 Apr. 2014. Web. 21 Oct. 2015.

Carroll, John. "UPDATED: FDA Spurns Sanofi's MS Drug Lemtrada on Fatally Flawed PhIII
Design." FierceBiotech. FierceBiotech, 30 Dec. 2013. Web. 21 Oct. 2015.

Garde, Damian. "Sanofi Rolls the Dice Again on Lemtrada after an FDA
Rejection." FierceBiotech. FierceBiotech, 30 May 2014. Web. 21 Oct. 2015.
Genzyme. "About Genzyme." Genzyme.com: About Genzyme. Genzyme, 30 June 2015. Web. 21 Oct. 2015.
Google. "Google Images." Google Images. Google, 2015. Web. 22 Nov. 2015.

PMLiVE. "Sanofi Persuades FDA to Back Its MS Drug Lemtrada." PMLiVE Site. PMLiVE, 17
Nov. 2014. Web. 21 Oct. 2015.

Salazar, Heather. The Case ManuelSanofi. "Our History." Sanofi. Sanofi, 17 Oct. 2014. Web. 21 Oct. 2015.

Sanofi. "Our Strategy." Sanofi. Sanofi, 20 Aug. 2015. Web. 22 Nov. 2015.

Staton, Tracy. "Sanofi Misled Investors with Rosy Lemtrada Predictions, Lawsuit
Alleges." FiercePharma. FiercePharma, 07 Apr. 2014. Web. 21 Oct. 2015.