We may have crossed a threshold in biopharmaceutical manufacturing some time ago and not even realized it. This paradigm mimics in several ways the decades of introductions and marketing of conventional (nonspecialty) drugs. Unfortunately, it could mean additional barriers to success for biosimilar manufacturers.
Payers (maybe less so the drug makers) recognize that the launch of brands that follow the first-in-its-class may not offer additional value, especially if priced at a premium. Often, these new agents were promoted as having a longer half-life, having fewer side effects, or simply were more effective than the class prototype. And in many cases, this proved correct. In other instances, the new drug was simply a different molecule with similar efficacy and safety. Payers referred to them as “me-too” agents, because they didn’t seem to offer advantages over the prototype. The phrase “me-too” connotes “no additional value.” In these cases, differentiating their value can be quite a challenge for the manufacturer, clinician, and payer alike. It is easy to see the economic and marketing importance of being the first to launch.
In migraine, for example, Imitrex® (sumatriptan) was approved in 1992, the first drug of the triptan class, to abort early-stage migraine attacks. Many other triptan agents followed, including Amerge (naratriptan), Axert (almotriptan), Frova (frovatriptan), Maxalt (rizatriptan), Relpax (eletriptan), and Zomig (zolmitriptan). The manufacturers of these other products did not intend necessarily to launch products that were third or fourth to the market. Imitrex had the advantage of being first approved as well as being available both in injectable and oral forms.
The development of agents like this may well occur concurrently; it is sometimes more a matter of timing and luck as to which one completes the clinical trials first and obtains FDA approval (without any hiccups). One may be just completing phase 1 as the other enters phase 3. On the other hand, some are developed well after the first launch. When these me-too agents hit the market, it is up to their manufacturers to figure out how to obtain preferred positioning. Other well-known examples include the statins for hypercholesterolemia, DPP-4s for diabetes, angiotensin-receptor blockers for hypertension, oral contraceptives, respiratory inhalants for asthma, and well, the list can go on ad nauseam.
With a great number of biologic agents on the market today, are several considered me-too agents? It is much more difficult to stick this label on a group of biologics because of several factors. For instance, their approved indications can be quite broad (e.g., anti-TNFs) and some members of the individual classes can only be received via infusion versus self-injection. The other consideration is that their effectiveness for all approved indications may not quite be the same (e.g., Enbrel® vs. Humira® for rheumatoid arthritis [RA] or for psoriasis). The frequency of administration can vary as well. Their mechanism of action may also be somewhat different (e.g., interleukin-17 vs. interleukin 12/23 inhibitors vs. interleukin 23 inhibitors).
Yet the number of members in the anti-TNF category and the burgeoning interleukin category does raise the question as to whether the clinical value of each biologic is substantially different. For some indications, like RA, the answer is that they are more similar than different. Remicade® was the first anti-TNF inhibitor approved, but the initial approval was for Crohn’s disease and only as an infusion (the RA indication came later). Enbrel, the first member of the class to be approved for RA, was launched as a self-injectable. Humira was approved at the end of 2002 for RA, and its other indications followed later.
Unlike other conventional me-too drug categories, the biologics have produced multiple blockbusters. Perhaps being early to market was more important than being first to launch. The anti-TNFs introduced later, like Cimzia® and Simponi®, have largely battled for remaining marketshare.
In the biologic category, the biosimilars Inflectra®, AmjevitaTM, ErelziTM, and RenflexisTM (when the latter 3 are launched)‑may even be considered me-too brands without substantial discounts and without interchangeable designations. Many payers already consider the approved biosimilars as new brands, because they are not inexpensive or interchangeable. If the me-too label sticks, their struggle up the value mountain could be steep indeed.