Earlier this month, Vanda submitted a Citizen Petition asking FDA to revoke the approval of Teva’s ANDA product for Hetlioz®(tasimelteon) Capsules, the sleep disorder drug. Vanda also asks FDA to remove the Teva product from the market. This Petition comes after Vanda lost its PIV case in December which case is pending appeal. (Citizen Petition: 2023P-1388).

Teva Bioequivalence Study Not Diverse Enough?

The thrust of Vanda’s argument is that Teva took “corner-cutting” measures yielding a “woefully inadequate study design.” The design flaw? Testing its generic product in a population of 58 males from India. Vanda argues that the drug is for a general population and that the bioequivalence study should have reflected a diverse U.S. population and include women and other ethnic groups. Vanda notes that FDA recommends that diverse populations be used for bioequivalence studies. However, in spite of this, FDA did not appear too concerned about the study design when it approved Teva’s application.

Diverse Studies for All Products?

At first blush, this argument seems to make sense. As a matter of statistics, it is always better – and more reliable – to have a representative sample. But the trip-up is that drugs – designed for humans – generally are metabolized in a similar fashion in all humans, regardless of gender, ethnicity, or any other sub-category. While each person may metabolize drugs slightly different, there is usually a predictable and reliable average and deviation of metabolic measures and efficacy.

However, there are a few drugs that do behave differently in different sub-groups of people. If this occurs, these differences are typically discovered when studied and approved for the first time and then reflected in its label. The Petition points to the original study which used a diverse cross-section of the U.S. population. But that is where it appears to end: there is no indication that Hetlioz is one of those exceptional drugs that behave differently in one group of people compared to another. While the Petition points to some possible differences, the product’s label does not.

The Implications

When drug companies file petitions to protect their products, I sometimes wonder if they have considered their logical implications. For example, is Vanda suggesting that 58 males from India do not reflect how an average human being would metabolize Hetlioz? While a dog, cat, or horse might metabolize Hetlioz differently, the men from India are human after all. The Hetlioz label contains no mention that men of Asian descent metabolize the product differently than anyone else.

Moreover, wouldn’t this argument place ANDA filers and FDA in an impossible position? What would “diversity” really look like? How many different categories of ethnic groups should an ANDA filer use? Five, six, twenty? Should they also use other forms of diversity such as geography, height, weight, diet, hair color, etc? Can FDA approve an ANDA even if Group B was underrepresented by 5%? How about 8%?

Is This Really About the Money?

It seems to me that, using the Petition’s logic, anyone could run to FDA — when it suits them – to argue that somebody else’s study did not meet the “diversity” criteria and that some sub-category was underrepresented which nullifies the study and application it supports. Hetlioz is an expensive product. A casual internet search places the retail price at about $25,000 per 30 capsules (that’s about $300,000 per year if taken daily). You can purchase a 30 day supply for a little less like $19,000 or a low of $7,800 with some coupons — perhaps these are the generic form.

It’s hard to start off 2023 with two blogs that are cynical. But it’s sort of hard not to be cynical at times. See Last Blog Post