Mary Caffrey

The biosimilars and generic drug industry is positioned for explosive growth, with $450 billion in pharmaceuticals coming off patent over the next decade amid an outcry in the United States over the cost of drugs.

And yet, there remains plenty of risk in the US market due to regulatory and legal hurdles—not to mention a combative political environment, according to executives who gathered last week during the “CEOs Unplugged” session at Access! 2022, held by the Association for Accessible Medicines (AAM) in Orlando.

“We've got no shortage of product opportunities and pipeline opportunities as an industry,” said Richard Saynor, CEO of Sandoz, as he offered a glimpse of the challenges ahead.

Dan Leonard, president and CEO of AAM, moderated the session that also featured Sven Dethlefs, PhD, executive vice president, North America Commercial, Teva; Vinita Gupta, CEO for Lupin Limited; and Chirag Patel, president and co-CEO, Amneal Pharmaceuticals.

Panelists first reflected on how their companies were moving forward from the pandemic, which caused havoc in supply chains and created challenges in keeping employees safe while delivering products. As group, the leaders praised their companies for responding to the challenges, which now include inflationary pressures. Leonard said the industry deserved credit for managing a supply chain that did bend, “but did not break.”

Teva’s Dethlefs said supply chain worries aren’t over. “I think we will face another 2 interesting years, even when the pandemic is behind us, it will somewhat continue through the procurement organization,” he said.

Leonard then turned to the generic and biosimilar pipeline. Dethlefs said the next decade could be as fruitful as the last one, for companies with careful strategy. “That requires generics companies to be more selective, to pick the right portfolio—because you cannot put a new granulation suite or manufacturing line behind every product,” he said. “That's not possible with the margins we earn.”

Dethlefs and Sandoz’s Saynor said the FDA approval process continues to lag Europe; while Gupta sees communication with FDA as much improved over the past decade, it’s come at a price in user fee costs. But a bigger challenge for biosimilars, Saynor said, is gaining acceptance in the US market, which means “getting payers and insurance companies to accept biosimilars,” the way generics have become part of the landscape.

“The US particularly presents a unique set of challenges that you just don't see from a European point of view,” said Saynor, who was taking part virtually from Switzerland.

Gupta and Patel agreed that complex generics offer the best opportunities, but as Patel explained, the risks are great, and the margins are small.

“Each biosimilar, each complex generics sometimes takes 5 years, 7 years,” he said. The returns to maintain investment in research and development are more than 10%, and the technology investment comes after that. “These are all risks. And we can do that if we are in the business.”

Leonard asked the group to reflect on the industry’s reputation: why, he asked, does the biosimilars industry face so many regulatory and legal hurdles when it saved US taxpayers $386 billion in 2021?

“Well, I’m going to use the term branding,” Patel said. “We have not done that effectively. We have to find new ways—it hasn’t been effective…. Look, we have the best story to tell. We just need to find the best storyteller to tell the story.”

As members of Congress get more and more calls for constituents upset about drug prices, he continued, “We don’t control it, so we shouldn’t, as an industry, take all those hits.” Generics, he said, have been portrayed by some as “bad guys,” when in fact, “We’re not. We’re actually good guys.”

Gupta agreed. She lamented the fact that President Joe Biden gave an extended speech on the high cost of drugs, yet the generic and biosimilars industry “does not come up once in that conversation.”

“Folks, we are the solution,” she said. “Look at the savings we bring.”

Going forward, Gupta said, the generics and biosimilars industry must be highly focused. Technology, she said, creates new pressures to avoid mistakes—that means picking the right products to develop and working closely with US and European regulators to get them approved.

“The hallmark of a successful generic company is strong planning, execution and efficiency. And in the past, you [could] do with 2 of the 3, and still be able to make reasonable return and continue to invest in a pipeline,” she said. “But not today. Now, you need to really be excellent at all 3 to be able to run the business.”

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There remains risk in the US market due to regulatory and legal hurdles—not to mention a combative political environment, according to executives who gathered last week during the “CEOs Unplugged” session at Access! 2022, held by the Association for Accessible Medicines (AAM) in Orlando.

Biosimilars CEOs: Opportunities Abound, but Regulatory, “Branding” Hurdles Remain

An official with the Center for Medicare and Medicaid Innovation (CMMI) told leaders from the generic and biosimilars industries that CMS is committed to policies that will expand the use of biosimilars, given the need to make drugs more affordable and “the potentially important role biosimilar adoption may have for the success of our value-based payment models.”

Purva Rawal, PhD, senior advisor and chief strategy officer for CMMI, spoke during the Association for Accessible Medicines (AAM) Access! annual meeting, which gathered in Orlando, Florida, February 15-16.

Most of Rawal’s talk focused on the “

,” a process that CMMI has undertaken to revamp how it implements alternative payment models; this is CMMI’s core mission under the Affordable Care Act. In an essay in 

 and in a white paper published last fall, CMS spelled out plans to add health equity to all models, and—of concern to the AAM audience—to renew its focus on limiting spending in Medicare and Medicaid.

“Importantly, we also want to increase the momentum and the movement toward value-based care and reignite that sense of inevitability that many of us felt 10 years ago,” Rawal said.

However, CMMI has been criticized for allowing the 

 (OCM) to run out this summer with no successor in its place, despite the investment made by practices to transition to value-based care. Rawal highlighted the OCM’s success in promoting biosimilar use while noting the model is set to expire.

“We're hearing about success in terms of participants prescribing lower-cost biosimilars, achieving savings in total cost of care, and maintaining quality outcomes, which is critical,” Rawal said. “So, we're hoping that these anecdotal reports of success show through in our future evaluation results.”

She explained how the payment policy that aimed to give specialty practices, including oncologists, incentives to prescribe biosimilars isn’t working as hoped. Under Medicare Part B, a practice would normally be paid less to prescribe a lower-priced alternative under the average sales price + 6% formula, but the law was written to prevent this revenue drop.

“The statutory payment policy theoretically incentivizes biosimilar use by making the drug add-on amount comparable across the reference biological and each biosimilar product. But this payment approach doesn't ensure that the prescribers’ margin on a biosimilar is comparable to the margin they may be able to obtain on the reference biological,” Rawal said. “So, we're starting to see some market competition, overall lowering of drug prices for biologicals, where biosimilars have been introduced. But the uptake of biosimilars has been slower than we anticipated, as many of you are aware, even with the add-on being based on the reference biologic.”

Rawal said the barriers that remain to biosimilar uptake are “concerning,” and CMMI seeks to remove them; some may be related to provider education, she said.

Acceptance among providers is complex, however. A recent 

 found that acceptance of biosimilars is much higher among oncologists than among rheumatologists. And oncologists have said that even when they prefer biosimilars, resistance may come from pharmacy benefit managers who demand that the practice use a higher-priced reference product.

Prioritizing affordability will work in biosimilars’ favor, she said, while crediting the AAM for providing ideas to promote biosimilar and generic use. Value-based care, she said, proved its worth during the pandemic and will do so going forward.

“We've seen early evidence that providers in population-based payments and alternative payment models were more resilient,” Rawal said. “That resilience allowed them to continue to provide access to patients, such as through telehealth.

“So, we have new evidence on the value of value-based payment, and value-based care from the pandemic, and we want to use this experience to accelerate our work to drive accountable care.”

Purva Rawal, PhD, senior advisor and chief strategy officer, Center for Medicare and Medicaid Innovation, spoke during the Association for Accessible Medicines' Access! annual meeting, which gathered in Orlando, Florida, February 15-16.

CMS Seeks Answers for Slower-Than-Expected Biosimilar Adoption, Rawal Says

As the US market awaits competition for Humira 

, a new study from Iceland shows how patient acceptance of adalimumab biosimilars may come down to the injection itself.

Adalimumab, developed by AbbVie as Humira, is a tumor necrosis factor-α inhibitor that treats autoimmune conditions including arthritis, plaque psoriasis, ankylosing spondylitis, and inflammatory bowel disease (IBD). With 

 reaching $19.8 billion in 2020, US health plans have been anxious to join their counterparts in Europe, where the drug has seen biosimilar competition since in 2018.

Iceland’s national health plan required patients to switch from Humira to the Samsung Bioepis biosimilar, 

, which had a different injection device and contained citrate, a chemical buffer used to maintain the medication’s stability. Now, a study published in 

 shows that both factors prompted negative feedback from about half of the patients taking part in a telephone survey following the switch.

The Humira device is lighter and features an activator button on one end, which the user must press with a finger or thumb to administer the medication. The Imraldi device does not have a button and is injected directly.

Led by Kristin Karlsdottir, PhD, MEd, of Landspitali University Hospital, and Anna I. Gunnarsdottir, PharmD, of the School of Health Sciences, University of Iceland, both in Reykjavik, the study involved gathering a list of all patients treated through Landspitali University Hospital who had switched from Humira to Imraldi under the protocol and contacting them for a phone interview about their experience with the change. Of the patients contacted, 84.5% agreed to participate. The average age was 50.8 years, 53.5% were female, and 96% self-administered the drug.

The study uncovered an important difference in the education method for the Imraldi switch compared with how patients learned to use Humira. While 90.5% of the patients stated they had received individualized instruction in how to use the Humira pen when they started taking adalimumab, only 18.2% received similar lessons for the Imraldi pen. Instead, most relied upon a letter from the hospital with printed instructions, which told them to call a doctor or nurse if they needed additional help.

Results from the phone survey were as follows:

Almost half (46.6%) found it more difficult to use the Imraldi pen than the Humira pen, while 12.5% found the Imraldi pen easier to use

Differences in the experiences were due to more painful insertion of the needle (62.2%) and that the insertion process was different (63.0%); however, needles on both pens are the same length and thickness

The authors reported that 62% of the patients did not feel any differences in grip of the 2 pens, but 23.5% of the patients thought the Imraldi grip was more difficult and 12.5% said the Humira grip was more difficult

By disease type, patients with IBD were most likely to report a difference with Imraldi and to report this pen was more painful, followed by patients with arthritis

Patients felt the needle insertion with the Imraldi pen caused a burning sensation “during and after the injection,” and some deliberatively prolonged the time between administration

These observations raise concerns about medication adherence, the authors wrote, and could be explained by the fact that the Imraldi injection contains more volume, including citrate (0.4 mL for Humira vs 0.8 mL for Imraldi). Because citrate had been removed from the Humira solution prior to the change to Imraldi, some patients told the investigators that “they perceived that they had returned to the ‘old’ Humira pen when they experienced this painful injection.”

The authors recommended that a more thorough, individualized education plan be part of any large-scale switch to a biosimilar medication that includes a delivery device. “Our results highlight the importance of thorough information, not only with an information letter but also with the possibilities for individualized introduction in planning switching to biosimilars,” they wrote.

Karlsdottir K, Gunnarsdottir AI, Grondal G, et al. A patients' perspective towards the injection devices for Humira and Imraldi in a nationwide switching program. 

. Published online January 27, 2022.  doi:10.3389/fmed.2022.799494

Iceland’s national health plan required patients to switch from Humira to the Samsung Bioepis biosimilar, Imraldi, which had a different injection device and contained citrate, a chemical buffer used to maintain the medication’s stability. 

In Iceland, Switch to Adalimumab Biosimilar Reveals Issues With Injection Device

Use of biosimilars will reach new therapeutic areas and new sites of care in 2022, as the industry prepares for competition with Humira, the top-selling drug in the world—an event that will mark a seismic shift not only in the pharmaceutical marketplace but across health care, according to a 

The year 2022 “is set to be a turning point,” in the United States, as biosimilars are on their way to delivering $133 billion in aggregate savings by 2025, according to, “2022 Biosimilars Report: The U.S. Journey and Path Ahead.”

“Total savings to patient out-of-pocket costs based on just the current biologics with biosimilars approved are estimated to reach up to $238 million,” predicted Heidi Hunter, president, Cardinal Health Specialty Solutions, in the report’s final section, which offered a forecast for 2022 and beyond.

Cardinal Health’s overview offered a primer on the landscape since the first supportive care biosimilars came on the scene in 2015, noting that specialists in oncology and, to a lesser degree, rheumatology have gained experience using these products; provider survey data contained in the report reflects this increased familiarity.

Biosimilars have already shaped the market, especially where payment models have encouraged their use. This is especially so in cancer care, where the Oncology Care Model in Medicare has rewarded participating practices for taking advantage of savings from biosimilars.

“Significant progress has been made in the adoption of biosimilars in the U.S., particularly in oncology, where all 3 classes of therapeutic oncology biosimilars (i.e., rituximab, bevacizumab, and trastuzumab) have exceeded 60% market share,” the report states. “Savings from biosimilars increased to approximately $8 billion in 2020 alone, more than tripling savings derived from previous years. In addition, for the first time in 7 years, oncology expenditure growth fell below 10% due to the impact of biosimilars and new product launches.”

Now, the report says, the field is poised to fulfill is promise of offering greater choice and holding down health care costs for more groups of patients, as biosimilar insulin and new products in ophthalmology reach the market. Hunter predicted these 5 trends for 2022:

Insulin will offer a test for interchangeable biosimilars. 

The year 2021 was light on approvals but Semglee, the interchangeable biosimilar for Lantus, packed a whallop. 

 (insulin glargine-yfgn), which has an FDA designation that allows pharmacist substitution without prescriber approval, will show how payers, pharmacy benefit managers (PBMs), and retail pharmacists will react to this FDA designation.

 As Humira (adalimumab) faces competition from up to 7 biosimilars next year, other rheumatology and immunology drugs are bracing for the fallout.

Retinal care will get most of the attention, as the number of patients with wet age-related macular degeneration rises and the cost per treatment remains $2000 on average. 

 (ranibizumab-nuna), the first biosimilar ophthalmology, was approved in September 2021 and appears likely to launch in June 2022.

 The Biden administration order for biosimilar approval transparency along with market transparency will help the cause. Rulemaking from FDA and actions by the Federal Trade Commission will support competition, and so will a new approach to payment models that promote biosimilar use in Medicare.

Use of real-world evidence will increase.

 This will provide particular insight into the effects of switching therapies.

While Cardinal’s report states that the best is yet to come for biosimilars, it doesn’t paint a bleak picture for these products. In fact, its provider survey finds that among those who are well-acquainted with biosimilars, comfort has never been higher with using the therapies—even switching patients to biosimilars during curative treatment. Among the findings of the provider survey:

Among the 4 categories of specialists surveyed—oncologists (N = 323), rheumatologists (N = 102), ophthalmologists (N = 102), and diabetes care specialists (N = 54)—only the ophthalmologists reported less than half (40%) being “very familiar” with biosimilars. Except for the ophthalmologists, more than 90% of the specialists were “very familiar” or “somewhat familiar” with the products.

67% of oncologists said they would prescribe biosimilars to a patient having success on a reference product regardless of payer considerations, while rheumatologists (35%) and diabetes care specialists (72%) were more likely to prescribe to existing patients if this was required by a payer or PBM.

More than 7 of 10 oncologists said they were “very” or “moderately” comfortable with automatic substitution of biosimilars, and only 5% said they would not subscribe biosimilars for indications without clinical trial data.

More than 90% of oncologists said they are comfortable with switching between biosimilars at least in some cases.

Cost savings to both patients and a practice are considerations for providers, although its degree of importance may vary. However, two-thirds of rheumatologists say that the economics of prescribing remain a barrier to biosimilar adoption.

The report describes “momentum” around bringing biosimilars to market as strong, and that the trend to move beyond oncology and rheumatology will define the next 5 years. 

“The year ahead is sure to include many significant biosimilar milestones,” the report states.

The year 2022 “is set to be a turning point” in the United States, as biosimilars are on their way to delivering $133 billion in aggregate savings by 2025, according to Cardinal Health's “2022 Biosimilars Report: The U.S. Journey and Path Ahead.”

Cardinal Health Report Sees 2022 as “Turning Point” for Biosimilars

The global pandemic of coronavirus disease 2019 (COVID-19) has wreaked havoc on every part of the pharmaceutical business, from purchasing patterns to drug launches, and the upheaval will continue when Medicaid enrollment booms, according to an industry expert.

Douglas M. Long, MBA, vice president of Industry Relations for IQVIA, surveyed the pandemic’s effects as he kicked off AMCP eLearning Days, a webinar series held in place of the annual meeting of the Academy of Managed Care Pharmacy (AMCP), which was canceled due to COVID-19.

Telemedicine’s explosion and the increased authority given pharmacists to help patients during the crisis could be positive changes that last, Long said. But his review of data shows that lockdowns and social distancing have been mostly disruptive to the healthcare system, and some players may not survive.

COVID-19 hit amid a period of overall good news for biosimilars and generics. These drugs were making an impact in the marketplace prior to recent lockdowns, and Long says they are much needed. Overall drug spending was up 4%, but the annual spike was 11% in specialty pharmacy and just 1% in traditional drugs.

Specialty sales had just about approached 50% of the market when the virus hit. Most of the late-stage pipeline growth is fueled by specialty and what Long called “niche” therapies. Long’s data show that 88.7% of prescriptions are to be dispensed as unbranded generics for 2020; unbranded and branded generics account for 20% of spending. In the past decade, he said, generics and biosimilars have saved $96 billion.

Last year saw a record number of biosimilar approvals, but many of these products do not launch.  “We are going to need specialty generics and biosimilars if we are to hold down spending going forward,” Long said.

Use of biosimilars in oncology “is starting to hit a critical mass,” he said. However, the focus on drug prices—or at least what people pay at the counter&mdash;has eased in the wake of COVID-19, and many reforms to help biosimilars reach the market were connected to that movement.

Medicaid enrollment could rise between 5 million and 10 million people, as record numbers of Americans lose jobs and employer-sponsored healthcare. Historically, Medicaid patients must wait longer to see a doctor, which could delay new prescriptions or refills.

Rates of prescription abandonment, which were already rising along with out-of-pocket costs, could increase, and the price at which patients leave drugs at the counter could fall.

Recently reported data show that 80% of clinicians are under “severe” or “close-to-severe” financial strain, and only 34% have cash on hand to last 4 weeks.

5% of clinicians have closed temporarily, and 61% are uncertain if they will be open after 4 weeks.

While telehealth visits have soared, with claims rising 1581% from prior levels by the week of March 27, the revenue will not offset losses from in-person visits, laboratory tests, and other income streams.

Overall, Long said, COVID-19 could lead to “an overall decline in health,” as patients delay being seen for new conditions, and new treatments are not started.

On the plus side, the number of physicians using telehealth for the first time rose more than 3000%. Like other experts, Long sees the rise of telemedicine as a phenomenon that’s here to stay. “It’s going to be hard to put that back in the bottle,” he said.

In the weeks leading into lockdowns, prescription purchasing patterns shifted to more 90-day fills, as patients stocked up on drugs they would need for the coming weeks. Long spotted spikes in prescriptions for a pair of drugs being used in a COVID-fighting cocktail: choloroquines and azithromycin (Zithromax), the HIV antiviral ritonavir, as well as tadalafil, sold as Cialis. Thus, Long will be eyeing June prescription figures to see whether patients get refills when the 90-day supplies run out, or whether any shortages emerge. Right now, he said, the biggest shortages are in sedatives used by hospitals.

COVID-19’s long-term fallout won’t be fully felt for months or years, as clinical trials stall and companies opt to delay drug launches. In response to a question, Long said it wouldn’t be a surprise if FDA is forced to delay some approval dates under the Prescription Drug User Fee Act (PDUFA).

Specialty drug administration is down 64.8% from pre-COVID levels, but the rate varies by disease area: treatments for multiple sclerosis, diabetic retinopathy and declined far less than cosmetic procedures and vaccines. In-office contraception treatments are down 55%, and new fertility treatments have plummeted 70%, while those who have cycles to use are moving to complete them.

“Oncology is holding up much better than expected,” Long said, although he would not be surprised to see a shift to oral oncolytics.

COVID-19 has increased attention on social determinants of health, he said, as issues such as poor housing, low incomes, and lack of education factor heavily in medication adherence rates. The worst state for adherence is Mississippi, followed by Texas; neither state has expanded Medicaid.

The unknowns in managed care pharmacy abound. When will people go back to work? How quickly will we recover? Both are hard to answer, especially with IQVIA’s own projections of a nationwide peak in the virus ranging from April 30 to May 11.

 And then, there is the biggest unknown of all: “Will there be a second round of this in the fall?”

Douglas M. Long, MBA, vice president of Industry Relations for IQVIA, surveyed COVID-19's effects on the pharmaceutical marketplace as he kicked off AMCP eLearning Days, a webinar series held in place of the annual meeting of the Academy of Managed Care Pharmacy (AMCP).

Amid Good Signs on Biosimilars, COVID-19 Upends Drug Purchasing Patterns 

Soumi Saha, PharmD, JD, senior director of advocacy, Premier, Inc

 I'm Mary Caffrey, here on behalf of the Center for Biosimilars®. We're here to welcome Dr Soumi Saha, senior director of advocacy at Premier. Welcome.

 So, we're here to discuss a new survey that has uncovered drug shortages that have been brought on by [coronavirus disease] COVID-19. And from your survey that was released last week it appears that with each passing day, we're seeing more and more shortages of the drugs that are designed to care for the COVID-19 patients. Can you talk to us about the major findings?

 Yeah, absolutely. So, Premier conducted this study from March 20th to 26th. It went to our over 4000 hospitals that Premier works with and 175,000 non-acute providers. From a response perspective, we had about 337 unique hospitals and health systems that responded as well as 100 non-acute sites that represented nursing homes, long-term care pharmacies, as well as home infusion pharmacies.

A couple key findings here: First, we did find that the acute settings are seeming to be having a harder time with drug shortages than the non-acute settings. That makes sense given the influx of patients that the acute settings are currently seeing. So, therefore, our recommendation would be that the immediate focus should be on ensuring acute settings have access to these drugs, but also realizing that non-acute settings are likely not far behind. The survey also focused on several classes of drugs that are specific for treating patients with COVID-19 and found throughout that regardless of where an entity was located, individuals are indicating shortages of antivirals and malarial drugs that are used to intubate patients, such as neuromuscular blockers, sedatives, and anesthetics. We've also seen shortages of IV fluids, antibiotics, as well as some typical fever and pain medications as simple as Tylenol or ibuprofen. What we also saw—not only is the demand for these drugs increasing, so folks are ordering more of them&mdash;but what we're also seeing is the fill rate is decreasing.

The fill rate refers to what you order versus what you receive in an order. And why we focus on that is any reduction in a fill rate below 100% typically indicates an early warning signal of a potential shortage or an oncoming shortage. So that's why it's so important to focus on those fill rates. That really tells us a lot.

 The figures that jumped out, of course, are the drugs that President Trump has discussed during the press briefings, particularly hydroxychloroquine. How much of the attention to this drug is warranted and how much of it is, maybe speculative? We've heard a lot about potential for hoarding, for people getting access to the drug that maybe shouldn't have access to it. Can you tell us a little bit about those, those things that are developing?

 Yeah, so great questions. And one of the challenges with COVID-19 is there are no known therapeutic cures or true therapies that we know definitively work. And one of the challenges is that anytime we see a study come out, regardless of the size of the patient population that it encompasses, if it has positive outcomes, we're immediately seeing a run on those drugs. And so, what's unclear right now is, “Is it hoarding, or is it appropriate stocking?” That's not clear yet. So, for hydroxychloroquine and chloroquine within 24 hours, we saw traditional supply chain channels absolutely depleted. And unfortunately, I think that's going to continue, as new therapies have positive outcomes from foreign sources.

It's clear and critical moving forward that an entity like CDC, for example, play a role where they help vet any of these studies that are coming from international sources and help determine their merit, so that we don't see this occurring in the future. And I can give you another example. There was a recent study in the past 96 hours that looked at ascorbic acid, and determined in a small patient population that ascorbic acid helped patients on ventilators get off that ventilator sooner rather than later. And that immediately overnight, you saw an increase in ordering for ascorbic acid and depletion on the supply chain channels.

 So, it's ascorbic acid. That's vitamin C, basically, correct?

 Yeah, okay. So, that's like a common drug. That's not something we would think about having a shortage of.

 [Drug Efficacy Study Implementation]. So, in the past few years, a new manufacturer came to market. It is a branded product now, sole manufacturer in the United States, and there are no generic alternatives available. So, the ability of that single manufacturer to ramp up production is limited. While it's a very common drug, and you think about it, as you know what you have in your orange juice, for example, from a drug perspective, it's not quite as simple because of the challenges with active inclusivity and other things.

 Wow. So, your survey found that the most acute shortages are, not surprisingly, are happening in the New York area! That makes sense. But could shortages quickly become a big problem in other parts of the country? And where might that happen?

 Absolutely. So, one thing that our study did was [it] looked at geographical areas when we focused on the 3 major hotspots that are known today: Washington State, California, and New York. And what we found was, as you mentioned, in New York, the shortage just seemed to be more imminent or drastic than what we're seeing based upon the national average. Now, what was interesting is that, when you look at Washington, shortages were not as high as in New York. And then shortages in California were technically higher than in New York. So, this got us thinking. Since Washington was the first major hotspot, are they not seeing the same level of shortages because they had full access to all available resources at that time? And are things in California worse than New York because New York is currently pulling resources away? From what otherwise would be available in California, or it could be due to regional distribution challenges as well. So, one of the big concerns that this survey seems to start illuminating is that what will happen for future hotspots? As disease progresses in areas like Chicago or New Orleans, for example, if New York is continuing to pull available resources, what is left for these additional hotspots that come online? And that's one of the big concerns moving forward.

 Well, a big takeaway from this survey is that these are not short-term problems. These are problems that are presenting themselves now, but are really long in the making. What are the top long- term issues that need to be addressed so that we don't find ourselves in this position ever again?

 Great. So, one [issue] is there's no single cause for shortages and so there can't be a single solution for shortages. In this particular case, most of the shortages we are seeing are due to just a sheer increase in volume and demand, not because of manufacturing issues or quality issues which we may otherwise see, but a few different things here. So, almost all of these drugs are produced internationally, or they're active pharmaceutical ingredients, which is the main component of these drugs is manufactured globally.

One thing that the [United States] could do is look at how do you incentivize onshore manufacturing of drugs that are considered critical moving forward? How do you identify capacity within the United States? How we can bring some of this manufacturing back domestically, immediately, and do so in conjunction with the FDA—because we would need a streamlined and very efficient FDA approval process. Normally, it takes months to years to have an abbreviated new drug application approved, but we don't have the luxury of time here. So, it would definitely have to be done in concert with the FDA.

 So, you've made a lot of recommendations on how what we should do next. There are regulatory solutions that you've talked about—and there are also financial incentives. I would say that those are kind of the 2 buckets that the solutions that you outlined fall into. What's more important that we do first, the regulatory solutions or those financial incentives? Where should we start?

 Thinking the short term, we need to start with the regulatory incentives, and work through streamlining and creating efficiencies in the process. So, we can begin onshore domestic manufacturing pretty immediately. The challenge is going to be long term, is going to be creating those financial incentives. Now, there was a provision that passed as part of the 

 that requires the National Academies of Medicine to study the foreign reliance on manufacturing for drugs and develop recommendations for how you incentivize financially or create those market based incentives for onshore manufacturing. So that's going to be a little bit more long term. But the short term is how do you work through that regulatory approval process to identify existing capacity that's already within—in the United States&mdash;and leverage that to create and manufacture the drugs that are of greatest need right now.

 One of the solutions you talk about is sharing among hospitals. And you know, just as [New York] Governor [Andrew] Cuomo has been talking about sharing—sharing the ventilators&mdash;maybe we should be sharing the supply and moving the supply around, but there's barriers to that. Can you talk about how that might work in the real world?

: Yeah, so there are several barriers to that. Typically, any hospital or any registered licensed pharmacy is limited to only being able to share a maximum of 5% of their inventory with another pharmacy without registering as a wholesale distributor, typically referred to as the 5% rule in pharmacy. So, one thing that we've asked is for the federal government to temporarily waive that 5% distribution rule. Many states would also have to provide a similar waiver because they have state based laws that mimic that. But that would at least allow us to move drugs from an area that doesn't have as great of a need to areas of greater need. So, if we find that there's a lot of hydroxychloroquine in South Dakota, for example, how quickly can they shift that product to entities in New Orleans, for example, as they come up and ramp up in need. And clearing that 5% distribution rule would allow hospital-to-hospital direct transfer versus having to go back through the wholesale distribution channel, which may cause delay….

 And probably add to cost as well, I would imagine.

 Okay. So, in the current crisis, some of the problems seem to stem from the fact that China has become such a big player in drug production, and Wuhan, which was the where it all began, in particular, has become a big focus not only in, in drug manufacturing, but also in the world of biosimilars. Right before all this happened, there had been an announcement for [Celltrion] to start construction on a major biosimilar plant. Should the United States take a bigger role in manufacturing its own drugs and we start to bring more than manufacturing back here?

 Yeah. That's one thing that Premier’s been speaking about for a while. We were huge proponents of the mitigating emergency drug shortages act components of which were included in pairs in sections 3111 and 3112. And so that's where that National Academies of Medicine report comes into play that would require the US government to look at that foreign reliance on manufacturing and look at how we incentivize domestic manufacturing of not only the finished product but also the active pharmaceutical ingredients as well. And we would like to see that for solid dosage forms sterile injectables as well as biosimilars.

 Okay. You mentioned some steps Congress has already taken. It’s expected that we're going to have more legislation pretty soon. What's the next thing Congress should put in the next bill that would help alleviate some of these problems?

 Yeah, so to your point about financial incentives Currently, the way it's written, those are a little bit more long term. But some of the things that we're thinking about are can we do some sort of tax benefits or tax cuts for pharmaceutical companies that are willing to step up to the plate, and help increase production of these critical drugs, potentially invoking the Defense Production Act [DPA] to include drugs as well, because that has not been done thus far, the DPA thus far has been limited to ventilators and personal protective equipment. And so that's kind of what we're thinking right now: How do we incentivize manufacturers to do that in the current state?

 Are there any success stories out there of drug sharing or drug transfer or production issues, any anything that's been done well, that's innovative that we should be doing more of?

 Well, one thing I would like to applaud is several of the drugs that are used to sedate patients in order to intubate them are controlled substances, fentanyl, for example, and fentanyl has been on the drug shortage list for quite some time. But in order to increase production of fentanyl, you also need to work collectively with the DEA in order to really additional product or quota to able manufacturers. And just last week, DEA did increase available quota to both manufacturers and 503. b outsourcing facilities for fentanyl. So, I do believe that that's a great success story that should hopefully help alleviate some of those shortages for fentanyl that we're seeing.

 Okay. And is there a drug shortage on the horizon that no one's paying attention to that we should be paying attention to?

 That's hard to tell. Because, again, anytime you're going to see any positive outcomes associated with any study from any source, you're going to see an immediate drug shortage of that product. I mentioned ascorbic acid earlier, but the reality is, is that we don't know what's next because we don't know what's going to come down the pike. And then we'll also have to be a little concerned about ancillary shortages as well. So, countries like India have export bans in place for 14 drugs and their corresponding API. Are we going to see additional countries put similar export bans in place that prevent the United States from obtaining those products? And then as the disease progresses globally, manufacturing shutdowns in several of these countries could potentially impact the drug supply chain as well. So right now, it's a little too soon to pinpoint exactly what the next shortages [will be], but the bottom line is, there will be more shortages, unfortunately.

 Well, thanks for joining us—and thanks for joining the Center for Biosimilars

Videos

Soumi Saha, PharmD, JD, senior director of advocacy at Premier, Inc, discusses drug shortages caused by coronavirus disease (COVID-19) and policy recommendations that could fix the problem.

Soumi Saha, PharmD, JD, Discusses COVID-19–Related Drug Shortages and Policy Solutions

The rebating landscape is among the factors that have made it tough for biosimilars to penetrate the US marketplace, but the launch of its biosimilar rituximab, Truxima, shows that Teva Pharmaceuticals has learned to navigate the system, the company’s chief executive officer said during his presentation at the 38th annual J.P. Morgan Healthcare Conference Monday.

Kåre Schultz took the audience through a review of Teva’s restructuring over the past 2 years, which called for dumping $3 billion in spending, trimming 12,000 employees, and selling or closing 13 manufacturing sites to address the company’s debt load. With the bad news out of the way, Schultz said, things are looking up for the leader in generic drug manufacturing.

For Teva, it’s “very interesting that we are now getting more into the biosimilar space,” he said.

Biosimilars have made less of an impact than they have in Europe “most likely due to the lack of understanding of the whole commercial setup, and what it takes to penetrate the US marketplace due to the complexity of rebating and contracting and so on,” Schultz said. An 

 published in the last week found that the legal barriers to market entry have hurt biosimilars uptake in the United States, compared with Europe.

Teva, Schultz said, has the volume and the contacts to overcome these challenges, as evidenced by the Truxima launch, which came in 

 at a 10% discount to Rituxan, the reference drug.

“I said at the previous third quarter announcement that we were aiming for double-digit share in this marketplace and sustainable profitability,” Schultz said. “We are not trying to take away everything, but we wanted the fair share of the market at a reasonable profitability, and I think that's exactly what we're going to prove with Truxima and future biosimilar launches.”

 have encouraged growth in the biosimilars market, but Schultz offered a different take. “There's a strong future, the way I see, it for both traditional generics and biosimilars in the US marketplace,” he said. “The pricing has now stabilized this debt spiral to the bottom, which got ignited by FDA approving more [abbreviated new drug applications] and by Indian and Chinese players getting into the marketplace; that has all stabilized. So, now we have a stable supply-demand situation working to the benefit of patients and the manufacturers.”

During the question-and-answer period, he elaborated on the dynamics of a biosimilars launch. “We see a stabilization of the margins in US generics, and we see biosimilars having, you could say, a slightly higher margin,” he said. “If you launch first with a chemical compound, you have a very good margin in the beginning and then it slows down pretty fast if you get a lot of competition.

“On biosimilars, you typically get less competition, your launch margin is probably little less than you could have on a traditional generic, but it stays longer because the pricing is much more stable due to less competition in that field and the fact that the barriers of entry to biosimilars are a lot higher.”

“Looking sort of into the future, we think that the basic supply and demand in US generics and biosimilars are favorable and are stable. That doesn't mean that we'll see a dramatic increase in margins, but we do believe that the plans we have for our whole manufacturing footprint will result in some improvements on the gross margin,” he said, adding that there will be more specifics during the company’s investor call on February 12, 2020.

Schultz chided media coverage of the pharmaceutical industry’s high prices and “taking advantages” of patients, saying that “the hard facts of the generic industry in the US is that it's actually the opposite that's taking place. The annual saving from generics and biosimilars in the US is around $300 billion. Teva alone supplies products with an annual saving of around $43 billion.”

“So,” he said, “the idea that generics are not sort of helping make pharmaceuticals and medicines affordable is basically flawed and not correct.”

 that 44 state attorneys general filed against Teva in May, which accused the drug maker of pricing fixing. Teva has denied the states’ allegations. Humana filed its own price-fixing claims in October.

Teva and Celltrion have also developed a biosimilar for trastuzumab, Herzuma. The companies 

 in July 2019 with Genentech, maker of the reference product, Herceptin. No US launch date for Herzuma has been disclosed.

The leading generic drug manufacturer launched Truxima, a biosimilar for rituximab, in November 2019 at a 10% discount to the reference product, Rituxan.

Teva's Schultz Sees Stability Ahead for US Biosimilar, Generic Marketplace

Compared with their European colleagues, Asian gastroenterologists have less confidence in biosimilars, according to survey results reported in the 

The report discussed results of a 17-question survey sent to members of the Asian Organization of Crohn’s and Colitis (AOCC). Initially, 320 members were randomly selected to participate, and 151 doctors from 8 Asian countries responded. The survey was done by email from February 24, 2017, to March 26, 2017. Nearly all respondents were gastroenterologists (96.6%), and 77.5% had cared for patients with inflammatory bowel disease (IBD) for at least 5 years.

Notably, just 6% of the Asian doctors said they felt confident using biosimilars in clinical practice. The finding was comparable with a 2013 survey of members of the European Crohn’s and Colitis Organization (ECCO), which found just 5% felt confident using biosimilars in practice; by 2015, however, that share had increased to 28.8%.

66.2% were aware that a biosimilar is “similar but not equivalent” to the reference drug

77.5% said cost savings are the main advantage of using biosimilars

38.4% were concerned about a different immunogenicity from the originator

19.2% of respondents considered biosimilars and the originator drug to be interchangeable

The 2015 ECCO survey had found that European doctors were more impressed with the cost savings and less concerned about a different immunogenicity than the Asian respondents. The ECCO results found:

In 2013, 89.5% said cost savings were the biggest advantage of using biosimilars; by 2015, the percentage had increased to 92.4%

In 2015, 16.9% said biosimilars work differently from their originator, down from 43% in 2013. In the AOCC survey, 19.9% said biosimilars work differently from the originator.

The 2015 ECCO survey found 27.1% of respondents were concerned about the immunogenicity of the biosimilar compared with the originator.

In the AOCC survey, 86.7% disagreed that pharmacists should automatically substitute biosimilars for originators, which was similar to the ECCO findings (85% in 2013 and 89.8% in 2015). When asked when substitution was appropriate, 62.3% of Korean physicians disagreed with automatic substitution in 

 case, compared with 38.8% of Japanese doctors and 11.8% of Chinese doctors.

The authors note that the first infliximab biosimilar, CT-P13 (Remsima, Celltrion) was manufactured by a Korean biopharmaceutical company and licensed in Korea in 2012. By 2017, 74.2% of the participants were from countries where this biosimilar was available, and the doctors were generally well-informed about what biosimilars are.

The share of physicians who prescribed biosimilars for more than 2 years was 41.5% in Korea, 20.6% in China, and less than 5% in other Asian countries. The authors noted that there is a relatively small price difference between biosimilars and originators in Asian markets compared with ECCO countries, which could explain the lack of uptake in some countries.

“Compared to ECCO members in 2015, Asian gastroenterologists had more concerns and less confidence about the use of biosimilars in clinical practice,” the authors concluded. “Thus, IBD-specific data on a comparison of the efficacy, safety, and immunogenicity in Asian patients will be needed.”

Park SK, Moon W, Kim ES, Park SH, Park D. Knowledge and viewpoints on biosimilar monoclonal antibodies among Asian physicians: comparison with European physicians. Korean J Gastroentrol. 2010;74(6):333-340.

Just 6% of the Asian doctors said they felt confident using biosimilars in clinical practice. A survey of European doctors found a similar confidence level in 2013, but that level had climbed to 28.8% by 2015.

Survey Finds Asian Gastroenterologists Report Less Confidence in Biosimilars

Acceptance of biosimilars in cancer care will require oncologists to demand just the right amount of data on these products, according to Gary Lyman, MD, MPH, of the Fred Hutchinson Cancer Research Center and the Seattle Cancer Care Alliance.

In a presentation last week during the annual conference of the National Comprehensive Care Network (NCCN), Lyman said oncologists need enough data to feel comfortable that biosimilars work as well as their reference products, but they cannot expect so much that the cost savings are wiped out.

“This would defeat one of the primary purposes of their development,” he explained. “But if we don’t require enough [data], while making the approval process easier—prices will come down&mdash;it will lower our confidence that adequate due diligence has been done.”

Finding that sweet spot remains a work in progress in the United States, where biosimilars have struggled, Lyman said. He encouraged the oncologists at the NCCN conference to look to the European experience as a guide. He noted that more than 25 biosimilars have been approved in the European Union since 2006, but that the monitoring system had not identified “any relevant difference in the nature, severity, or frequency of adverse effects between biosimilar medicines and their reference medicines” in 10 years.

Both the FDA and the European Medicines Agency require ongoing monitoring of the manufacturing processes for all biologics, which Lyman said is essential to ensure quality and safety.

Much of Lyman’s presentation was aimed at giving those unfamiliar with biosimilars an overview of why these biologics can offer a way to ensure patient access to innovative biologics, including those developed for cancer treatment. He presented data from IMS Health that show global spending on biologics continues to outpace that of spending on pharmaceuticals overall, reaching $221 billion in 2017.

He reviewed FDA evidence requirements for biosimilars as well as the March 2015 approval of the first US biosimilar, filgrastim, sold as Zarxio, a granulocyte colony-colony stimulating factor (G-CSF). Filgrastim biosimilars that reference the originator product, Neupogen, remain among the most common worldwide, although Lyman noted that there are other 

 of interest to the oncologist; 1 each for rituximab and bevacizumab, and 4 different ones that reference trastuzumab.

He pointed to updated areas of the 2019 NCCN guidelines, using prostate cancer as an example, and showed where different G-CSF products are listed for treatment of neutropenia: the prostate cancer guideline included 2 biosimilar versions of G-CSF, Zarxio and Nivestym, as well as tbo-filgrastim (Granix), which was approved before the biosimilar pathway existed. It also included 2 products that reference pegfilgrastim, Fulphila and Udenyca.

Lyman also took note of the 2018 FDA approval for Retacrit, which references epoetin alfa, a medication that stimulates erythropoiesis and is used to treat anemia that occurs in chronic kidney disease associated with chemotherapy. The NCCN update in prostate cancer states, “The panel extrapolates that there would be no clinically meaningful difference for treatment of [chemotherapy induced anemia].”

Lyman explained that physicians remain skeptical about biosimilars and fear that payers or health systems will force their use for cost reasons. The availability of strong clinical data will be essential to ensure that clinicians accept biosimilars, he said.

“NCCN is very concerned that we have access to the data that the FDA have,” he said. Whether the guidelines committees get the data from FDA or directly from the manufactures, Lyman said, it is essential to have this information so that biosimilars can be integrated into the guidelines going forward.

The naming convention is extremely important, so that if there are adverse effects, providers know which biosimilar was used. “If we don’t know or if our patients don’t know what form of trastuzumab was used, that’s an injustice to our patients,” he said.

He pointed to a May 2018 policy statement from the American Society of Clinical Oncology, for which he served as lead author, which discussed naming and regulatory considerations, safety and efficacy, interchangeability, switching, and substitution; the value of biosimilars, and provider and patient education.

There’s no question, Lyman said, that “biosimilars will be playing an important role.”

Lyman GH, Balaban E, Diaz M, et al. American Society of Clinical Oncology statement: biosimilars in oncology. 

The presentation at the National Comprehensive Cancer Network reviewed regulatory requirements and updates in the 2019 guidelines that affected biosimilars.