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Data Exclusivity and Bio-Similars: Both More and Less Than It Seems

FDA Matters has been very upbeat about the prospects for the bio-similar marketplace. “Smart money” (i.e. companies currently making billions from their ability to discover or license new bio-pharmaceuticals and market them) decided to play before they knew the ground rules on exclusivity and patents. We can only conclude that there must be substantial amounts of money to be made, regardless of the specifics.

With this in mind, FDA Matters explores why there is a persistent belief that the bio-pharmaceutical industry got something better than data exclusivity. I also explore whether data exclusivity will really provide valuable protection for original reference biologic products.

Those who keep referring to market exclusivity under the new law point to the fact that FDA can’t approve a bio-similar under the abbreviated bio-similar pathway until 12 years after the original, reference drug was first approved. That sounds like market exclusivity.

My understanding of the BIO interpretation: it doesn’t prevent another company from going and generating its own data and getting its own approval through the existing BLA approval pathway. Hence, all that is protected is the company’s data.

The new law “protects” the reference product from competitors….by denying competitors the benefits of the new approval pathway for 12 years. It is not market exclusivity because there are other ways to get a bio-similar approved. It is more than just data exclusivity because the competitive product can have its own data and still not be able to use the new abbreviated pathway for approval.

What has been granted to the reference product is “pathway exclusivity” for 12 years.

This suggests that the market is going to divide. Those who wish to market bio-similars of drugs that were approved more than 12 years ago will have a choice between the abbreviated pathway and filing a full BLA application for approval. For those who wish to market bio-similars of drugs that were first approved less than 12 years ago, the choices are: wait or go the full BLA route.

Many companies—even those with the opportunity to take the abbreviated pathway– are going to decide that the advantages of a full BLA exceed the cost of collecting additional data. Some will take the data from their European bio-similar approvals and talk with FDA about which pathway will work best. Others will work toward approval of BLAs for so-called “bio-betters.” These are new products that are bio-similar to an existing product, but are safer, more effective or easier to use.

What comes next depends in part on FDA. The new law clearly empowers FDA to find ways to get more bio-similar products on the market. Since this can only be partially achieved through the abbreviated pathway, I believe the agency will be looking for ways to make the BLA process friendlier for bio-similar and bio-better products.

FDA approval of a bio-similar will not assure a marketplace unless other changes occur. I envision health plans, insurers and government programs shifting toward “therapeutic substitution,” where lower-priced bio-similar products will be put on formularies in place of the original reference product.

This has already occurred in the statin market, where an increasing percentage of prescriptions are filled with a generic statin, regardless of whether the doctor wants the patient to have a brand product. Right now, it seems like a stretch for bio-similars to be subject to therapeutic substitution, but FDA approvals of bio-similars and bio-betters will open up this possibility. Insurers needing to save money (and companies willing to lower prices to gain market share) will do the rest.

This brings me back to my other point: that the bio-pharmaceutical industry will find that the benefits of data exclusivity (and pathway exclusivity) will prove to be much less valuable than they seem now. BLAs are going to get easier, the marketplace will start substituting therapeutically, and all that “smart money” will prove to have been well-invested.

What do you think? Post a comment.


For those readers who want to familiarize themselves with what the new law says, it is pages 686 to 703 at: http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=111_cong_bills&docid=f:h3590enr.txt.pdf

More on bio-betters: “Pfizer Pushes on New Biotech Drugs”


2 Responses to “Data Exclusivity and Bio-Similars: Both More and Less Than It Seems”

  1. biotech says:

    Recent legislation left many things totally unclear regarding data exclusivity that were not mentioned in today’s column/blog. For further information on the topics I bring up below, see my recent commentary on these topics at http://www.biosimilars.com (look for the red text label in the right-hand column).

    Among its failings, the recent law neglects to ever define “reference product,” leaving opportunities for infinite “evergreening” through serial BLAs. You, like many, as indicated in your commentary, appear to simply presume that the granting of a full BLA confers data exclusivity. But BLA approvals do not define products, and BLAs were never meant to do this. For example, Extavia (recombinant interferon beta-1b) from Novartis received its own full BLA, but is simply rebranded (relabeled) Betaseron from Bayer Schering; and Xyntha from Wyeth received a full BLA, with the only changes from its prior version being removal of animal-dervived products from its manufacture/formulation. Do these and other products that happen to receive a BLA (rather than a sBLA usually granted for such changes) deserve 12 years of data exclusivity? Any sponsor can get a full BLA simply by making a change, any change (like putting a new name on the label or making a process improvement that changes little or nothing of substance) and receive a full BLA. So BLAs are useless in terms of being a basis to judge whether a product/approval should receive data exclusivity or not, i.e., whether it is new, innovative, its development was costly, or whatever criteria are to be used to define a reference product. [What criteria should be used?] If FDA does not grant exclusivity to all BLAs (which is the easiest thing to do, but allows infinite evergreening), then the agency will have to make official rulings about what is really a new product or not (whether a BLA represents a new product or not for purposes of data exclusivity), much as it does for orphan products.

    Another important area that Congress totally ignored (probably where last minute compromises, like with “evergreening,” involved simply removing all relevant language), was the issue of names to be used for biosimilars. Everyone assumes unique names will be used, and language regarding this was in earlier iterations of the legislation. But the final legislation makes no mention of names, not even using the word “name” once. Thus, although FDA will surely require unique names for biosimilars (nothing new), it is totally unclear what type of name this will be (e.g., trade name/trademark; total arbitrary/meaningless; a name indicative of product class; a name indicative of relationship to reference product; a USAN (INN; which are rather dysfunctional for many reasons and uses); active agent name with company appended; etc. And who will propose and select unique names – the sponsor, FDA, a third party, etc?

    Otherwise, another Congressional blunder (or shrewd move by innovators) I did not mention was the seeming requirement for biosimilars to only be approvable for currently-marketed, not historical, reference products. Can simply removing a product from marketing prevent all future biosimilar versions (a very attractive route for those with products facing biosimilar competition, with most every biosimilar candidate product likely already having a 2nd-generation or other replacement product(s) on the market by the time patents run out)? That seems to be the case. For example, if I were Amgen, I would seriously consider removing Epogen/Procrit from the U.S. market a few years before patent expiration (biosimilar competition), tell everyone to use the newer, better, safer, etc., 2nd-generation Aranesp (also from Amgen), and with no in-date U.S. Epogen/Procrit available for comparisons for biosimilar approval, including for clinical trials, there will simply never be an Epogen/Procrit biosimilar approved by FDA (through a biosimilar mechanism). Couple these problems with the failure to define “reference product” and the requirement (seemingly) that biosimilars be very similar to their reference product such that similar expression systems must be used (e.g., can’t compare a plant- vs. mammalian cell-expressed product), and widely-held expectations for biosimilar competition and cost-savings may simply never develop.

    In general, biosimilar and consumer advocates, activists, etc. failed abysmally with this legislation. They got suckered in, diverted and concentrated on no-win, largely extraneous issues, such as number of years data exclusivity, while largely ignoring or ever publicly calling for definitive answers to more basic and all-important technical issues (whether due to incompetence and/or ignorance). Much as the slogan “process=product” worked to stall biosimilar legislation for years, biosimilar proponents (e.g., GPhA) and consumer advocates repeatedly failed to grasp that they need to get technical in their arguments and questions, and that they will lose, and lose big, if they solely concentrate on politics, posturing, appealing only to the public and politicians, etc., and ignore the underlying basics, the technical/technological aspects (the hard parts), when it comes to pharmaceutical regulation.

  2. Biotech—I feel your pain about the flaws in the new bio-similar legislation. I don’t think the Senate version was ever intended to be the last word, but it is. At a meeting last week, three people spoke abut the problems with the law. Their lists don’t even overlap with yours! And I am told the patent part of the Act is even more dysfunctional.

    I am still betting that “the smart money” will find a way to profit in the bio-similar/bio-better world. And in an earlier column, I predicted the bio-similar market would be dynamic and unpredictable. Static or even linear modeling might not tell us what comes next.

    Perhaps the key is the following point from my article:
    What comes next depends in part on FDA. The new law clearly empowers FDA to find ways to get more bio-similar products on the market. Since this can only be partially achieved through the abbreviated pathway, I believe the agency will be looking for ways to make the BLA process friendlier for bio-similar and bio-better products.

    I think the abbreviated pathway will be used, but new BLA’s are likely to dominate the world of bio-similars. Costs to enter this market are going to come down dramatically over the next 5 to 8 years, meaning products with less than $1 billion will also start to get some action. With all the money to be made and medium-sized players mixing with some of the larger companies, things will happen….maybe despite the law rather than because of it.

    If we can anticipate the ground rules, they might be: get your own data for a BLA, don’t violate anyone’s patent(s), and prepare to discount in order to get market share. It will never be like the small-molecule generic world, but with biologics costing upwards of $300,000 or more per year….a 20% discount is serious money. One of my upcoming posts will be on the new law’s different treatment of orphan drugs.

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