In several recent articles, I discussed a meeting I attended in Brazil hosted by the Ministry of Health and the pharmaceutical trade organization Grupo FarmaBrasil. After a day of presentations highlighting Europe’s experiences, possible educational strategies, and a rheumatologist’s perspective on biosimilars, the speakers — including myself — attended a private meeting between the Ministry of Health, Grupo FarmaBrasil, and the regulatory body, Agência Nacional de Vigilância Sanitária (ANVISA). During the meeting, the Ministry officials shared the goals of the Productive Development Partnership (PDP) program for biosimilars and the approval/pricing process for new medicines. But there are a number of market challenges, including innovator pricing schemes, which could stand in the way of the government purchasing biosimilars in large volumes.
In order to increase the nation’s use of biosimilars, the Ministry of Health is planning to implement a national biologics and biosimilars policy. During the private meeting, there was a particularly interesting discussion between Ministry officials and fellow speaker Nikolai Brun of the Danish Medicines Agency about Denmark’s experience transitioning patients to biosimilars and establishing a pharmacovigilance program for all biologics. The safety and efficacy profiles of biosimilars are not well known throughout Brazil. As such, there is interest in implementing an interchangeability policy and new technologies to track nation-wide biologics use and real-world evidence. Overall, in this article I hope to continue capturing some of the Ministry’s biggest questions, as these are particularly telling of how the nation’s biosimilar policy could take shape in the future.
Post-Marketing Surveillance And Big Data Peak Interest
As I wrote in a previous article, the government is facing great pressure from physicians in particular to implement an interchangeability policy. Many physicians would like to see additional clinical data from biosimilars following a switch. When the Ministry guided discussion toward interchangeability, there were naturally quite a few questions addressed to Brun about the Danish Medicines Agency’s decision to require switching.
If we think about the nations that have had great biosimilar uptake, Norway often takes the Scandinavian spotlight. But Denmark has had just as successful an experience with biosimilar uptake and post-marketing surveillance. As Brun described, all patients in Denmark (barring the non-stable ones) were required to transition to the biosimilar. This is why the country boasts a 98 percent rate of uptake of Remsima (infliximab) and upwards of 80 percent on Benepali (etanercept) in a mere two years.
Now, it’s important to note that Denmark has the benefit of being a wealthy and small country with a homogenous population of 6 million. Because of this, the country’s biosimilar implementation methods will not be wholly feasible in Brazil, which has upwards of 160 million people relying on its public healthcare system. Much of the country is also afflicted with great poverty.
But the Ministry of Health was particularly interested to hear Brun’s thoughts on interchangeability in Denmark and post-marketing surveillance. Denmark, like many other EU countries, does not have an interchangeability policy in place. The decision to transition is typically at the discretion of the physician, and automatic substitution at the pharmacy is not an option. As I noted earlier, Danish patients were required to transition to the biosimilar. Therefore, it should come as no surprise to anyone that this decision was originally met with a lot of skepticism.
However, to ensure this decision remained sound, the country required a two-year period of increased pharmacovigilance for both the biologic and the biosimilar. To this day, once a biosimilar hits the market, physicians are required to report all adverse events (regardless of causality) that may occur in patients while taking the medications. (As you can already guess, these efforts have not turned up any significant differences in treatment with a biosimilar or the reference product.)
As Brazil aims to reassure about safety and efficacy and weighs its options for pharmacovigilance and potential interchangeability policies, Denmark’s experience provides an interesting alternative to a strict interchangeability policy. Indeed, one of the questions posed at the meeting was if the country could simply establish a similar pharmacovigilance program, as opposed to an interchangeability policy. As Brun reassured, putting an adverse event reporting protocol in place was a great help in building trust amongst physicians and patients in Denmark.
Now, in a country the size of Brazil, implementing a working pharmacovigilance system will be a different animal than in Denmark. But it was interesting to hear a member of the Ministry of Health engage Brun in a discussion on the potential use of Big Data to determine switching patterns. One of the most interesting aspects of this discussion was the claim that the introduction of biosimilars could lead to the incorporation of technologies that may have been originally overlooked or refused in the past. One of the potential strategies outlined was that to find a way to capture the data and use modeling to extrapolate to Brazil’s population. This technique could determine access and usage patterns of a drug throughout the country. (In many cases, we’re seeing nations begin to explore similar modes of inquiry, a good example of this being the U.K.’s BioValue program. Similarly, in the U.S., the BBCIC has goals to analyze switching patterns between the innovator anti-TNF agents, which will ultimately create the basis for a future descriptive analysis study of biosimilar switching in the U.S.)
Medicines Access & Procurement: Needs Renewed Focus, Ongoing Analysis
Another aspect that will require some finessing within the country is the procurement process —especially when it comes to informing the necessary stakeholders about treatment changes. Though Silveira spoke up in support of biosimilars, one challenge she faces is particularly dangerous for patients. The decision was made at a high level to switch to a biosimilar from the innovator Remicade. However, there was no notice or discussion at the physician level about this change. This posed a particular challenge for Silveira who required higher doses of Remicade which, as she found out, were no longer covered under the SUS. Similarly, following the change, there was a four-month supply disruption, leaving patients without access to the treatment.
Obviously, this is a deeply problematic situation, but it brings up two critical needs. For one, there must be education and a method of communication across the supply chain to ensure all parties are on the same page about a new medicine transition. Secondly, as Brun noted, supply security is a critical aspect the regulators look at when selecting a biosimilar in Denmark. Price and quality are important, but, at the end of the day, supply security must also be considered — especially when multiple manufacturers begin to enter the market.
As the biosimilar market in Brazil continues to grow over the course of the next few years, the industry will also need to keep tabs on the numbers of patients who are using these treatments. And, naturally, pricing will be a key influence in access and use of these products. For instance, if the biosimilar becomes 70 percent cheaper, uptake will surely increase. So, what was originally 10,000 patients relying on the biosimilar will become 30,000 patients. It will be critical for the Ministry of Health and other government parties to be able to consistently track and forecast usage in the future so they can have early conversations with biosimilar manufacturers about supply. Manufacturers will need this information well in advance to ensure they can supply the appropriate amount of the drug.
In what could be a good start to this process, the Ministry of Health told us it is implementing a national poll to get a sense of patients’ access to biologics. In doing so, the agency will get a better sense of access levels and needs to address in the forthcoming national biologics and biosimilars policy. I dare say the biosimilar manufacturers in the country, as well as myself, are waiting anxiously to see what shape this policy will take and just how far the government plans to jump into the biosimilars realm.