From The Editor | March 19, 2019

How Can Manufacturers, Oncologists Prepare For The Oncology Biosimilar Boom?

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By Anna Rose Welch, Editorial & Community Director, Advancing RNA


<p>A few months ago, I read <a href="">a fabulous Q&amp;A in <em>Managed Care Magazine</em></a> featuring oncologist Gary Lyman and co-director of the Hutchinson Institute for Cancer Outcomes Research at the Fred Hutchinson Cancer Research Center. In this day and age, we regularly come across surveys or discussions emphasizing how much more work we have to do in the education realm to ensure physicians&rsquo; comfort with biosimilars. But after reading Lyman&rsquo;s interview on one cold, dreary January day, I felt buoyed. That&rsquo;s not to say there isn&rsquo;t more work to be done, of course. But it was reassuring to see a prominent member of the oncology community express such comfort and confidence in biosimilars.</p> <p>Throughout the interview with <em>Managed Care Magazine</em>, Lyman discussed his work with the American Society of Clinical Oncology&rsquo;s (ASCO&rsquo;s) Biosimilars Work Group, which released a white paper in support of biosimilars in the oncology treatment paradigm last year (a huge deal). As a hematologist specializing in breast cancer therapies, a researcher in supportive care, and an expert in healthcare economics, he not only demonstrated understanding of biologic molecules and their inherent batch-to-batch differences, but he also presented a realistic and optimistic view of current and future pricing schemes for biosimilars. (I urge you to read his original interview if you haven&rsquo;t already. And, for a similarly well-thought-out European perspective, check out <a href="">this Q&amp;A article with oncologist Rosa Giuliani</a> from the European Society for Medical Oncology.)</p> <p>After reading the article, I knew I had to speak with Lyman myself. I had many questions, most of which centered around the experiences and education that increased his faith in biosimilars. I also wanted to pick his brain on how the industry can ensure the necessary information about biosimilars reaches oncology physicians. What followed was a conversation highlighting some of the dynamics playing out in the hospital setting for biosimilars, as well as how physicians and drugmakers can foster a greater understanding of biosimilar medicines.</p> <p><strong>Building The Appropriate Foundation Of Knowledge </strong></p> <p>As more complex oncology treatments approach the market, we&rsquo;ve heard that, in general, oncologists are excited for the arrival of biosimilars because of their savings potential. After all, as new, innovative (and expensive) cancer treatments are introduced on the market, biosimilars will lower costs and free up overall healthcare spend to cover these novel treatments. But, of course, these products also have to be developed in a cost-effective manner to provide a long-term solution. &nbsp;</p> <p>I found Lyman&rsquo;s respect for and understanding of the efficient biosimilar development pathway to be particularly refreshing. Having sat on the FDA&rsquo;s Oncologic Drug Advisory Committee for eight years, he&rsquo;s intimately aware of the work that goes into developing novel biologic treatments.</p> <p>&ldquo;With biosimilars, we understood from the very beginning that, if we required the same amount of clinical trial evidence, then we would defeat at least one of our primary goals, which is to bring competition and introduce lower prices,&rdquo; Lyman shared. &ldquo;We understood from the regulatory standpoint that the FDA had to find a more efficient way to assure themselves and clinicians that biosimilars were as close as a molecule can get to its originator. They put all their focus on preclinical work and the molecular characterization. In fact, the molecular characterization of these biosimilar agents is far more detailed and multifaceted than in the past.&rdquo;</p> <p>Throughout his <em>Managed Care Magazine</em> interview and during ours, as well, Lyman emphasized a commonly misunderstood or unknown fact &mdash; that even originators differ from batch to batch.</p> <p>However, I&rsquo;d argue Lyman remains an exception among clinicians in terms of biosimilar education. Knowledge levels are certainly improving, Lyman added; he&rsquo;s seen the needle move from very little awareness to a more comprehensive understanding of the development and regulatory pathway for these drugs. &ldquo;A portion of oncologists better understand some of the regulatory concepts,&rdquo; he shared. &ldquo;But they&rsquo;re hungry for more. They realize this is a train that has left the station and biosimilars are entering their practices.&rdquo;</p> <p>As he pointed out, for example, there still is hesitance to use biosimilars as a curative treatment &mdash; even amongst physicians who understand biosimilars. For instance, he called attention to the uptake of rituximab biosimilars in Europe, particularly in Germany. According to a recent survey, oncologists and clinicians are more likely to use biosimilars as supportive therapy. &ldquo;They&rsquo;re still using the originator to treat the types of lymphoma that have a high probability of a cure,&rdquo; said Lyman. &ldquo;There&rsquo;s still some concern about being the first one to use one of these biosimilar cancer treatments outside of the supportive care arena. But I think this will change&mdash;in fact, perhaps it&rsquo;s already starting to.&rdquo;</p> <p>He acknowledged the positive experience thus far in Europe, of course, as well as the fact that biosimilars have been integrated into the ASCO and National Comprehensive Cancer Network guidelines. Indeed, ASCO&rsquo;s acceptance of biosimilars (along with several other large physician and patient groups) was one of the biggest triumphs I noted in my <a href="">Top 5 Biosimilar Developments of 2018 article</a> a few months ago. Not only do clinicians rely on these organizations for their own education and treatment advances, but payers do as well. In many cases, payers take into account professional societies&rsquo; recommendations when building their formularies to ensure they&rsquo;re doing right by the patient community.</p> <p>A truth commonly relayed from conference podiums in this industry is the importance of the payer in the biosimilar acceptance and uptake equation. In fact, we consider these stakeholders to be a major force in driving the transition to biosimilars. However, we&rsquo;re also aware of the tensions this influence introduces in the physician community. U.S. clinicians (and certain patient groups as well) have spoken out about having other parties interfere in the treatment decision-making process. Lyman acknowledged this tension but remained optimistic these concerns will decrease over time, especially given oncologists&rsquo; keen understand of rising healthcare costs and their impact on the treatment landscape.</p> <p>&ldquo;If we get data in the coming years that prices are coming down and patients are benefiting from both the economic and the medical standpoint, many of physicians&rsquo; concerns and fears will fall away,&rdquo; he ventured &mdash; as long as the FDA remains dedicated to pharmacovigilance of these products over time.</p> <p><strong>How Can Biosimilar Trust Become More Mainstream?</strong></p> <p>During the last few years under Commissioner Scott Gottlieb&rsquo;s command, the FDA has strived to make the biosimilar development approval process more efficient. One change the agency made to the process is to only hold large committee reviews for the first biosimilar of each reference product. When I asked Lyman his thoughts or concerns about steps being taken to evolve biosimilar development, he pointed specifically to the FDA&rsquo;s decision to eliminate these large committee reviews. Though he acknowledged they are not always necessary, he argued the lack of transparency surrounding the scientific data is a big concern among the clinician community &mdash; including himself. &ldquo;The importance of the professional community&rsquo;s access to the evidence supporting the approval of biosimilars &mdash; ideally published in the peer-reviewed literature &mdash; cannot be overstated,&rdquo; he said.</p> <p>&ldquo;I think the message to the FDA and to manufacturers is, if you believe in the drug, get the results out there,&rdquo; he suggested. &ldquo;If the FDA decides not to have an expert advisory panel review the data, then it should put the data that was submitted out into the public domain, so professionals and guideline developers can review that evidence and likely come to the same conclusion as the FDA did internally.&rdquo; In fact, given the abbreviated development pathway for biosimilars, he emphasized it&rsquo;s even more critical for the FDA and manufacturers to highlight the evidence submitted for approval.</p> <p>A question I&rsquo;ve been asking different stakeholders is how they have been using the scores of published real-world evidence (RWE). I was particularly interested to learn what impact (if any) this evidence is already having in the clinician community. After all, the development of biosimilars centers around analytical characterization, and not clinical trials, which is a large paradigm shift. Since we saw two pegfilgrastim biosimilars approved without efficacy clinical data last year, it begged the question of whether the data we&rsquo;re already publishing about positive real-world performance is efficiently reaching the right eyes or falling by the wayside.&nbsp;</p> <p>One of the most common places Lyman sees this data being published today is in managed care journals typically geared more toward administrators or payers than to clinicians. Some of this has to do with the notion that much of the RWE and information about manufacturing changes and &ldquo;drift&rdquo;&mdash; all of which are critical for physicians to understand &mdash; may be considered too technical for the broad clinical audience reading journals like the <em>Journal of Clinical Oncology</em>, <em>JAMA Oncology</em>, and <em>The New England Journal of Medicine</em>. Lyman did reference one biosimilar-related publication in the <em>Journal of Oncology Practice, </em>but, as he noted, it was in a supplement as opposed to the primary journal. &ldquo;We really need to continue to have biosimilars more prominently discussed in the public domain,&rdquo; he said.</p> <p>For manufacturers, this means publication in peer-reviewed literature &mdash; which some companies have actively been exploring &mdash; as well as dedicated websites. He emphasized there&rsquo;s still much work payers, providers, pharma, and regulatory agencies need to do to enhance education on biosimilars because, for busy clinicians, even keeping up with the launching of originator drugs in oncology is daunting.</p> <p>But on the clinicians&rsquo; end, he continues to urge there be educational sessions dedicated to biosimilars at major meetings &mdash; and not just as satellite sessions, where they&rsquo;re so often relegated today. &ldquo;We&rsquo;re pushing more and more that biosimilar education programs become part of the meetings, as opposed to relying solely on industry requests to provide education sessions,&rdquo; Lyman offered. &ldquo;Ideally, ASCO, The American Society of Hematology, American College of Radiology, and European Society for Medical Oncology will hold symposiums on biosimilars during the main meeting as this will raise the credibility of the material that&rsquo;s presented, and it will draw in the attendees at the meeting.&rdquo;</p> <p><strong>Biosimilar Pricing: Only One Piece Of The Puzzle</strong></p> <p>A topic that&rsquo;s growing increasingly important in the U.S. (and especially in Europe) is responsible pricing practices. In his original interview with <em>Managed Care Magazine</em>, a question was posed to Lyman about the current 15 to 30 percent discounts for biosimilars in the U.S. &mdash; and whether these were in any way disappointing. I respected Lyman&rsquo;s grounded response that we will not be seeing 70 to 80 percent reductions in price as we&rsquo;ve seen with generics. But this does require realignment of expectations. &ldquo;A 10, 20, and hopefully even 30 percent reduction in the price of a multi-billion-dollar industry is still big money,&rdquo; he argued. &ldquo;Spread across diseases and entities, and with multiple agents in a therapeutic class, biosimilars have the potential to save millions, if not billions, of dollars for the healthcare system.&rdquo;</p> <p>When I asked if and how he incorporates that long-term view-point into his own educational efforts, he admitted it&rsquo;s complicated, especially since we currently have only sparse short-term savings data from Zarxio in the U.S. But he also mentioned the importance of broadening the overall biosimilar discussion to include the challenges posed by rising costs and the consolidation of health systems. Today, there are innovative new technologies, therapies, and advanced imaging techniques increasing the burden on the overall healthcare system. As these costs increase, so do patients&rsquo; overall cost-sharing responsibilities.</p> <p>Though he hopes biosimilars will be one positive solution to rising costs, he also cautions there are bigger issues that need to be addressed. &ldquo;If we don&rsquo;t address the bigger issues of healthcare delivery and the cost of optimal cancer care treatment and management, we still will not see the necessary reductions in healthcare costs in the U.S.,&rdquo; he warned. &ldquo;Biosimilars are a good first step, but there are structural changes that need to be made,&rdquo; whether this means enforcing stricter hospital pricing practices or cracking down on extraneous medical procedures.</p> <p>&ldquo;There&rsquo;s a lot of work across the whole spectrum of healthcare delivery that we need to focus on,&rdquo; he concluded. &ldquo;But as a clinician and an oncologist, I can begin to make inroads through biosimilars and have an important impact. I want to convince my colleagues to become more knowledgeable about these treatments, as well as play a key role in their introduction to the U.S. healthcare system.&rdquo; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;</p>