The far-reaching changes in the political environment today in the US and in Europe may affect the approval and regulation of pharmaceuticals, including biosimilars. The incoming Trump Administration has expressed its repeated desire to repeal the Affordable Care Act (ACA) (of which the Biologics Price Competition and Innovation Act [BPCIA] is a part), finally giving the Republican Congress firm support in their repetitive attempts to repeal.
On the other side of the pond, the United Kingdom populace’s vote on a referendum to leave the European Union has caused consternation for many. From the pharmaceutical perspective, the UK is a dominant force in the region’s drug regulator, the European Medicines Agency. This could lead to tricky times ahead. Dr. Gillian Woollett keeps a close eye on the global biosimilar industry for Avalere, a Washington, DC–based consulting organization. We caught up to Dr. Woollett for a few minutes to ask her what it all means.
Biosimilars Reviews & Reports: Donald Trump is our new President-Elect. He has stated that one of his top priorities is to address the ACA. What can he or can’t he do that will affect, intentionally or unintentionally, biosimilar regulation and acceptance?
GILLIAN WOOLLETT, MA, DPhil: It’s worth remembering that the biosimilars pathway is Title VII of the ACA. If he attempts a broad repeal, we may not have a biosimilar pathway.
However, the expectation is that broadly speaking little will change; they will spare the biosimilar legislation.
BR&R: What about other aspects of the BPCIA?
WOOLLETT: Clearly, the intellectual property challenges are a fairly significant part. Approval by the FDA is only one step in the process. On the other hand, we also have the FDA user-fee negotiations coming up next year (for conventional drug regulation as well as biosimilars) Those user fees are “must-pass” legislation needed to fund the FDA.
There is some opportunity for other aspects of FDA oversight, timeliness, [and] prioritization. We’ve seen the 21st Century Cures Act be enacted by Congress, but there are still additional aspirations that could be added to the user fee acts. Some of the most pressing challenges for the biosimilar regulatory environment are the overall regulatory predictability—namely, timeliness of meetings and approval decisions, plus the backlog in reviews which have apparently missed their action dates at FDA.
Congress has a tremendous opportunity to influence these challenges. It is not clear exactly how it will be handled, because it is more than just biosimilars: Part of the reason that the biosimilar approval process is slow relates to the fact that the conventional drug approval process is cumbersome.
BR&R: This doesn’t bode well for the pipeline, does it?
WOOLLETT: The pipeline in the biotech space more broadly is very full, but the speed of development and approval is still slow. The FDA’s rate of approvals has gone up recently, but it is not high compared with the number of products that are in development. At the current rate of approval, it could take decades for the products in the pipeline today to reach the market and patients.
If that could change, there may be greater opportunities for all products, including biosimilars. After all the pipeline for biosimilars is that of the originator biologics. This does not mean the standards need to be relaxed, but a greater focus on what defines a products can enable the extent of the clinical trial dossiers to be lessened. This would also help lower the cost of and time for bringing new drugs to the market, and maybe prices on the market.
INTELLECTUAL PROPERTY, PATENTS, AND TORT REFORM
BR&R: Perhaps the greatest problem hindering the availability of biosimilars today relates to IP—the maze of patents and the patent dance—and the need for tort reform. But that’s not historically a priority of a Republican administration, especially as it affects business.
WOOLLETT: Certainly, for the first cohort of biosimilars, the 12-year exclusivity has been utterly irrelevant to the launching of a new product. In one case, the reference product [filgrastim] was 24 years old at the time its biosimilar was approved.
Clearly, the exclusivity has received a lot of attention but it is not actually the rate-limiting step right now. The complexity of the “patent dance” is fairly extreme. As currently determined by the federal courts, the patent dance is elective, and sponsors don’t have to choose to pursue it. This may well now be affirmed by the Supreme Court who have agreed to take a case that may consider this in addition to whether the 180 days’ notice of intention to market can only be made post-FDA approval. Also, the courts said you have to have the biosimilar application submitted before you can contest a patent, which was the case with Enbrel and the “submarine patent” [Editor’s Note: A patent that was filed pre-1995 but issued more recently and still gets the pre-GATT exclusivity (17 years from date of issuance)], which goes out to 2028. It could be argued that all of the patent dance provisions are completely unnecessary as the biotech industry has historically defended it patents in the courts just like every other industry absent any complex additional provisions.
Really, about 80% of all of the BPCIA statutory language comprises this so-called patent dance and could be removed. That is not to say any of the intellectual property and patent questions would ever be simply resolved, and I am not suggesting that you can take away anyone’s patent rights. It is just how and when you reconcile them, and whether you need an entirely new and complex process specific to biosimilars to do so. I would suggest that you don’t.
THE BREXIT AND BIOSIMILARS
BR&R: Europe has its own problems, some of which are self-inflicted, like the Brexit. What are the implications of the Brexit for the EMA?
WOOLLETT: I have hoped that Brexit would never happen, but recently the UK Prime Minister has reaffirmed her opinion that Britain will exit. The referendum was only ever advisory, and clearly with the Parliamentary involvement things may still change. But to the extent, at some point, Article 50 is filed, Britain would have 2 years to exit the EU. The EMA is based in London, and if it were to move, then there’s an issue that they lose a lot of their expertise in all likelihood. The Brits provide a considerable amount of the expertise available to the EMA, and likely wouldn’t have visas to work in Europe even were they to want to move. There are 860 employees at EMA, and the supposition is that we’re talking about loss of roughly half its workforce.
Certainly, Britain and Germany have been major contributors to the expertise in the evaluation of biotech products, and it would be a significant loss. Would it really slow things down? If the Brexit takes another couple years, and if the EMA moved to a popular city, they would probably be able to hire. And there would be some continuity, one would hope. Maybe some of that EMA expertise could be available to the FDA, given its own shortages and inabilities to hire.
BR&R: Actually, how does the approval time at the EMA stack up against that for the FDA? Is it shorter? Is it the same?
WOOLLETT: I don’t know. I would have to check exactly what it is. We do know that the EMA has 100% performance against its action dates because of how it is set up. The FDA does not.
Yes, and there’s two decisions: One is the regulatory recommendation of the approval by EMA and then a fixed-date later—I believe it’s 69 days—the European Commission grants the full marketing authorization. So, there’s a little bit more predictability in Europe around a lot of these decisions. Plus EMA now has considerably more experience with biosimilars.
INTERDEPENDENCE FOR BIOSIMILAR INDUSTRY SURVIVAL
BR&R: It is becoming increasingly apparent that we’ll need to be exceedingly careful to nurture the biosimilar industry. There is a level of interdependence that the stakeholders, including industry, have, with regard to ensuring that biosimilars will achieve significant cost reductions in the specialty pharmaceutical area, as well as improving patient access to these biologics.
WOOLLETT: Yes. There is no question that biosimilars alone cannot rescue the US health care system from itself. There are aligned incentives that will be necessary to make biosimilars able to both reduce prices, make specialty drugs more competitive, get marketshare as a consequence, and create a sustainable competitive marketplace for biologics going forward. It is very clear that biosimilar sponsors cannot do that alone. It is not a pure pricing play, but to the extent that payers use the availability of biosimilars to gain lower prices from the reference brands, we will not see many biosimilars available in the US. The biosimilar sponsors who offer lower prices have to be able to get marketshare as a result. That’s still a question in Europe. The 28 countries are seeing very different outcomes in terms of pricing, access, and affordability, depending on the nature of their health care system decisions, and the incentives they create–and that’s with single payers. The US has multiple payers both public and commercial, and is way more complicated.
BR&R: This hasn’t been the case yet in the US: The first 2 biosimilars (Zarxio® and Inflectra®) were introduced at a modest discount, not counting proprietary rebates. But the introduction of multiple biosimilars could drive prices down to levels that may deter manufacturers from developing new agents.
Thank you, Dr. Woollett, for a very interesting discussion.