By Anna Rose Welch, Director, Cell & Gene Collaborative
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One of the biggest trends of 2016 is surely going to be the emergence of the biosimilar market in the U.S. following the launch of the first product (Zarxio) in recent months. Biosimilars have been available in the EU for roughly 10 years, but in the U.S. there are still a number of key decisions that need to be made regarding a biosimilar’s name, label, and interchangeability. As such, the U.S. regulatory pathway is still taking shape. We spoke with some industry experts to get their predictions as to what the most important biopharmaceutical industry trends will be in 2016 and how those trends will affect the biosimilar market.
What biopharmaceutical trends are you most excited about, and why? How do you expect these trends will impact the biosimilar market into 2016?
"Significant clinical advances are now being made in biopharmaceutical therapies which are meeting previously unmet clinical needs. The costs of these therapies, though, are putting unprecedented strain on drug budgets and an increasing demand for patient access. As biologics prices continue to rise in 2016, the industry is going to be paying closer attention to biosimilars and their cost advantages."
"You’re going to start seeing more complex products come into the market with the biologic-manufactured products, and I think that will begin to tailor how the biosimilar market is actually going to evolve in the U.S. It will be very interesting to see some of the first antibodies that get to market. I think those are the more complex molecules. You saw Sandoz’s approval, which was a protein, but not a glycosylate antibody. When you start to get into the more complex molecules, we need to watch if the FDA continues its trend of approving biosimilars with full extrapolation and full brand labels, or if it’s going to start to limit the labels to what trials were done."
"We are living in an exciting time for the biopharmaceutical industry. Innovative therapies that doctors — including myself — could once only dream of are now available to treat patients with chronic diseases. However, the costs of some of these treatments are exorbitant. In response to this, increasing the availability of cost-effective biosimilars will play a huge role, allowing more patients to reap the benefits of the life-changing drugs made possible through medical advancements, without crippling healthcare systems."
"I would highlight the progress on immuno-oncology. This area is an outstanding example of how biopharmaceutical trends appropriately follow the science and create truly breakthrough therapies — in this case by harnessing and stimulating our own immune systems to fight diseases such as cancer. The approval of checkpoint inhibitors marks only the beginning of this new era in medicines. This ongoing innovation continues to create wonderful opportunities for patients but also great opportunities for biosimilars now and in the future. That is, biosimilars currently being developed can help offset costs of older biologics that are off patent, allowing health systems to create headroom in their budgets to fund these newer innovations. As we have seen in Europe and other countries, biosimilars create competition, which leads to savings for healthcare systems and increased access for patients."
"We’re working very aggressively on preparing for the next round of the Biosimilar User Fee Act."
Biosimilar Trends That Could Be Problematic In 2016
It’s no secret that, when it comes to the U.S. biosimilar market, there are still many important decisions that need to be made by the FDA. The agency’s rulings on naming, interchangeability, and labeling will no doubt determine the uptake of biosimilars and the initial success of the market in the U.S. But among biosimilar experts, there are also concerns related to patents and data exclusivity for reference products that could also be problematic for the growth of the global biosimilar market. Pfenex’s Liang says there are still a number of questions pertaining to the resolution of the Trans-Pacific Partnership (TPP) negotiations. “Globally, more clarity is required in the interpretation of the TPP’s exclusivity period for biologics — whether this is a period of market exclusivity or data exclusivity — to understand potential ramifications on biosimilar market growth in the future.”
In addition to concerns about data exclusivity of biologics, those paying attention to the rise of the biosimilar market should look at what is happening in courtrooms with the patent dance and biologics patent challenges. Both Liang and Wheeler address the 351(k) pathway and the impact its formation will have on the rise of the biosimilar market. As Liang states, “Similar to the Hatch-Waxman legislation which created the generics industry, decisions by the courts also will play a large and impactful role in clarifying the 351(k) pathway, with significant ramifications in 2016 — and obviously beyond — for the pathway for biosimilar development in the U.S.”
In fact, Wheeler singles out the 351(k) pathway as being one of the biggest complications for the biosimilar legal clearance process. He homes in on the Federal Circuit’s final decision regarding the Amgen v. Sandoz “patent dance.” “This whole patent exchange, which is already being litigated, makes it much more complicated than the generics side of the world where there’s the Orange Book, and you know what patents you’re dealing with before you even start developing a program,” says Wheeler. There is also the matter of the inter partes review (IPR) process, which promises a more timely and cheaper method of challenging patents. In fact, it is currently being employed by biosimilar makers such as Momenta. However, branded pharmaceutical makers are arguing in favor of patent reform legislation that would bar generics and biosimilar makers from using the process to get their products to market more quickly. As Wheeler says, questions remain, such as, “How long will the IPR process take, and will the IPR process continue to be accessible to biosimilar makers with some of the patent reforms that are actually out there?”
Education: The Biggest Goal Of 2016 Biosimilar Industry
Drug companies, regulators, doctors, patients, and payers all hold the keys to the success of the 2016 biosimilar market. In order to build a sustainable biosimilar market, more education will be needed to address doctor and patient hesitation to ensure these medicines are prescribed. Companies will need to remain stalwart in navigating the evolving U.S. regulatory pathway amidst ongoing lobbying efforts and emerging global regulations. Here, Life Science Leader’s panel of biosimilar experts share how the industry and their companies plan to address the challenges currently facing biosimilars moving into 2016.
How are you/your organization preparing to face these trends in 2016?
"We must continue educating policymakers about the potentially far-reaching implications of biosimilar regulations in the U.S., as well as the globally impactful Trans-Pacific Partnership (TPP) deal. We are confident that leaders in both the U.S. and globally will enact policies to support the development of biosimilars. As board chair of the Biosimilars Council, I spend a considerable amount of time within these educational efforts. In particular, within the Biosimilars Council and at Pfenex, we are focused on explaining to legislators the science behind biosimilars, including the safety and efficacy of these therapeutics, particularly given the decade of experience in other geographies such as the EU and Australia. Through ongoing meetings with policy and decision makers, we continue to inform on the important role of biosimilars in the future of the U.S. healthcare system and the value that increased patient access and competition can bring. We are committed to advancing this dialogue and offering research and insights to all stakeholders, from patients to physicians to lawmakers and regulators."
"We continue to advance our pipeline of biosimilars and expect to make several new biosimilar regulatory submissions in 2016. We will focus on increasing uptake of our first biosimilar in the U.S. and preparing for launches of our next generation biosimilars, both in the U.S. and EU. Globally, we will also continue our outreach and advocacy efforts to improve stakeholder understanding and acceptance of the biosimilar concept, as this is key for the continued growth of this industry."
"We’re working very aggressively on preparing for the next round of the Biosimilar User Fee Act (BsUFA) negotiations. We’re doing so to make sure the pathway allows us to actually use the technology and science we have and to try to abbreviate the trials necessary to get extrapolation and interchangeability more quickly. Our company’s approach to biosimilars is built on designing products that have fingerprint-like similarity. We are trying to engineer biosimilars that are very, very close to the brand and remove any residual uncertainties through our characterization and understanding of the products and our engineering them. It’s very important to us that the FDA pathway allows us to take advantage of the technology investments we’re making and to be able to gain efficiencies in the approval process."
"Lobbying by originator companies is being used as an effective tool to create doubt within the biosimilar market. Biosimilar companies will need to address policymakers to reinforce the positioning of biosimilar medicines within a clinician's armamentarium as a tool to increase patient access and provide the ability to treat more patients for less cost."
The Countries/ Companies That Will Make The Biggest Impact On The Global Biosimilar Market In 2016
To date, a majority of companies exploring biosimilar development has chosen to direct their energies toward the more established EU market. However, despite the current strength of the EU market, it was surprising to discover that most of the experts we interviewed did not choose the EU market as the one to watch for 2016. So where are they directing their attention?
"We expect payers to increase their efforts to support the uptake of biosimilars.
According to Tim deGavre, the chair of the biosimilar sector group of the British Generic Manufacturers Association, the U.S. is poised to make the biggest difference in the space because of its scale and because it is tackling important decisions related to interchangeability and naming. He calls attention to the recent approval and release of Sandoz’s Zarxio, along with the FDA’s ongoing review of several other biosimilar applications, including etanercept and infliximab, as being important steps for the growth of the global biosimilar market.
Liang also singles out the U.S. because of the FDA’s recent efforts to clarify the biosimilar regulatory pathway. According to him, “A recent report found the FDA has spent more hours reviewing biosimilar applications in 2015 than in the three previous years combined. This momentum is anticipated to continue, and 2016 is when we expect to really see the industry blossom.” In addition to the FDA’s efforts, McCamish draws attention to payers, stating “We expect payers to increase their efforts to support the uptake of biosimilars, both in the U.S. as well as in the EU.”
But beyond the efforts of the FDA and the size of the country, Wheeler is focusing on some of the players within the U.S. In particular, he identifies the recent Pfizer and Hospira merger which led to the creation of a large and highly reputed biosimilar portfolio. According to Wheeler, the Pfizer and Hospira deal “is quite a potent combination in the marketplace. The resulting company could actually make some real waves with the combination of portfolios it’s going to have with that merger.”
The 2016 Biosimilar Market: A View From The U.K.
While the U.S. market introduced its first biosimilar medicine only several months ago, biosimilars have been available in the U.K. since 2006. Recently, England’s National Health Service (NHS) took proactive steps toward promoting biosimilar education in order to bolster market growth and consumer/doctor faith in these cost-saving biologics. When it comes to looking ahead into 2016, Tim deGavre, chair of the biosimilar sector group of the British Generic Manufacturers Association (BGMA), says the industry, and especially the U.K., should expect to see continued growth in the biosimilar market.
As patents expire for reference molecules, biosimilar makers will be ramping up their development to bolster the biosimilar pipeline, ushering in a large number of cost-effective drugs for patients suffering from rheumatoid arthritis, cancer, and diabetes. In the face of a growing number of highly priced biologic drugs targeting the aforementioned indications, deGavre says the U.K. should expect to see the biosimilar market lead to hundreds of millions of pounds of potential savings for the NHS. In particular, deGavre references a study that examined the cost burden of using human growth hormone (hGH) and the impact the uptake of hGH biosimilars could have on annual healthcare. “Data based on 2010 usage of hGH at The North Central London Formulary and Medicines Management Group at University College London Hospitals NHS Trust suggests annual cost savings in excess of £200,000 [$300,000] per annum are possible from a single center if all patients were switched from originator hGH to biosimilar hGH,” says deGavre.
However, there are a number of roadblocks that could prevent the U.K. biosimilar market from achieving growth in 2016. For one, deGavre says there are issues with the decision-making process within the U.K. which stand to impact biosimilar prescribing habits. For instance, deGavre says there are an increasing number of decision points on the path to prescribing a medication, as the NHS has left the decisionmaking process to locally accountable organizations. “We are seeing a lack of clarity and high levels of variation as to who is responsible for making the decisions in each locality, resulting in some inertia in decision making in new and complex areas of medicine,” deGavre states. “This is creating significant variability in decision making in the take-up of all medicines but especially in new medicines such as biosimilars.” deGavre calls attention to Norway and Denmark as examples of how a national approach can lead to significant uptake of biosimilars. Norway in particular has turned heads with its 69 percent discount — a discount so steep, it has made it difficult for prescribers to resist the biosimilar. According to an article published by Bloomberg in April 2015, this discount on Orion Oyj’s biosimilar of Remicade led doctors to increasingly prescribe the biosimilar, which quickly captured 50 percent of the Remicade market.
Much like in the U.S., deGavre also points to the number of concerns that persist about the quality, safety, and efficacy of biosimilars in the U.K. There is still a general need for acceptance of the science of biosimilars, the Medicines and Healthcare products Regulatory Agency (MHRA) pathway, and extrapolation. “In extrapolation, a biosimilar only needs to prove it is safe and effective in the most 'sensitive indication,'" explains deGavre. “Where the mode of action is the same, clinical studies for each of the additional indications are not required. Communicating this important principle of biosimilarity will be critical to the acceptance and use of biosimilars in the U.K.”
The NHS has taken a key step toward improving biosimilars communication and education to decision makers in the U.K. In recent months, the NHS collaborated with several organizations, including the Association of the British Pharmaceutical Industry (ABPI), The National Institute For Health and Care Excellence (NICE), and the BGMA, to release a document entitled What Is A Biosimilar Medicine? The purpose of this document, as described in its introduction, is to “provide an update for key clinical and nonclinical stakeholders about the developing role of biosimilar medicines in the NHS in England and to support the safe, effective, and consistent use of all biological medicines, including biosimilar medicines, to the benefit of patients.”
"We are seeing a lack of clarity and high levels of variation as to who is responsible for making the decisions in each locality."
Tim DeGavre, chair of the British Biosimilars Association
Following this document’s release, there was a national and regional stakeholders program launched to encourage the local uptake of biosimilars. In fact, this partnership between the NHS and the BGMA is going to continue into 2016 to actively promote the biosimilar opportunity. The association biosimilar expert sector group which deGavre chairs is entering 2016 with a goal of continuing to partner with patient groups, healthcare professionals, regulators, and NHS commissioners “to increase the understanding and drive a sustainable environment for the development, production, and optimized use of biosimilar medicines in the U.K.,” deGavre says. He also stresses the importance of conferences for furthering industry education as the biosimilar market advances. In particular, he cites The European Biosimilars Conference, which will be taking place in London on April 28-29, 2016. “The BGMA will ensure the U.K.’s participation in the upcoming conference, which, in turn, will enhance the nation’s focus on building the biosimilar market,” deGavre says.