The ‘Duck Test’ for Huey, Dewey and Louie: the legal case on CDK4/6 inhibitors

Me-too drugs (drugs with the same mode of action for the same indication) are generally beneficial to society as they provide variation, choice and price competition. However, companies market their drugs as unique and superior, rather than me-too products, even when the mechanism of action and chemical structure are very similar. This leads to discussions on similarity and uniqueness, as we will illustrate by the case of a triplet of breast cancer drugs.

The figure below shows the structures of two CDK4/6 inhibitors: the upper structure is palbociclib, a drug developed by Pfizer, the first company to create this category of drugs, while the lower structure is ribociclib, a drug from Novartis with a similar structure.

Three “me-too”, costly drugs

A new class of drugs, used for the treatment of hormone-sensitive breast cancer, is CDK4/6 inhibitors. There are three of them on the market: palbociclib (Pfizer), ribociclib (Novartis) and abemaciclib (Eli Lilly). The similarity of the chemical structure of two of them are shown in the figure. All three have shown similar outcomes on the primary endpoint of progression-free survival; and although palbociclib did not meet the secondary endpoint of overall survival, there is no statistically significant difference in overall survival between these therapies. In addition, the side effects appear to be somewhat similar, though the frequency of each side-effect may vary between drugs. None of these therapies are cost-effective. In fact, claims data from the United States shows that adding CDK4/6 inhibitors to treatment costs approximately $70,000 for each extra month the disease is delayed.

An effort to create market dynamics in the Netherlands

Up until January 2025, the Dutch government had negotiated price arrangements for all three drugs. This meant that the health system received a discount but paid the same price for each drug, as the government was not allowed to pay one company less than another for similar drugs.

To create a market dynamic, the government recently delegated the negotiations to the payers.

But things went wrong…

In the Dutch system, as long as a drug is under government control (especially therapies with a high budget impact), companies are obliged to offer discounts to ensure their drug is cost-effective; otherwise, the drug is not reimbursed. However, now that the responsibility has been handed over to the payers, companies no longer feel obligated to make financial arrangements. As a result, only one company, Pfizer—the one with the largest market share—stepped forward to the payers to make financial arrangements.

Novartis went to court

Novartis decided not to compete by making a price arrangement with the payers or directly with the hospitals, but instead took the matter to court to stop payers from creating competition. They claimed that their drug was superior because it had overall survival data and a different side effect profile.

Last week, the court ruled in Novartis' favour.

The judge decided that based on the most recent scientific research (i.e., palbociclib's secondary endpoint for overall survival was not significant), it could not be maintained that the three CDK4/6 inhibitors were equal. As a result, payers had to immediately stop their financial arrangements. This was a major victory for Novartis, as the company could now set its own price with no interference from payers or governmental obligation to offer any discounts.

In a culture with a collective ethos and a healthcare system based on solidarity, as the Netherlands has, irrespective of the final decision, the judge could have said, "Your drug should still be cost-effective; otherwise, it will displace other care and disadvantage other patients." But the judge didn’t.

Superiority cannot be claimed

Reading the court ruling brings to mind a proceeding by the National Advertising Division (NAD), a self-regulation program of the industry in the United States. In 2022, when the overall survival data for Novartis' drug was published, the company launched a campaign referring to their CDK4/6 inhibitor as the only drug in class with a consistently proven overall survival benefit in breast cancer. Eli Lilly, the third competitor, filed a challenge, claiming that Novartis' message was unsupported due to the absence of a head-to-head study. NAD found that although Novartis' drug, ribociclib, had the longest median overall survival, they couldn't demonstrate that the methodologies in the studies, patient characteristics, or other elements were similar enough to allow a valid comparison between drugs. Superiority could therefore not be claimed.

Shortly after, the FDA also fired back regarding the promotional communication of Novartis on ribociclib, as it created a misleading and false impression about the drug’s efficacy and impact on quality of life.

The Duck Test

The development of a me-too product is less risky and therefore more profitable for companies. The needed comparative data between drugs are often never delivered to discourage any comparison. In this case, the largest real-world study, involving nearly 10,000 patients in the United States, shows no significant overall survival differences between the three CDK4/6 inhibitors.

For us these questions remain: how can the healthcare system ensure competition rather than turning me-too drugs into separate monopolies? Does stopping competition and causing higher prices violate antitrust law? And finally, how can the legal system support and stimulate competition when faced with a complex legal case like this?

Do you remember Huey, Dewey and Louie, Donald Duck's identical triplet nephews? Perhaps the court could use the 'duck test': if it walks like a duck, swims like a duck and quacks like a duck, it is… a duck! If a me-too drug has a comparable structure, if the mechanism of action is similar, and if the indication granted by EMA or FDA is similar, then it’s reasonable to conclude that the drugs are close enough to be treated as the same.