Tony Hagen is senior managing editor for The Center for Biosimilars

Considering Alvotech doesn't have any biosimilars approved, some may question why the company is signing biosimilar distribution deals all over the globe. The answer, according to Joseph E. McClellan, PhD, MBA, Alvotech's chief scientific officer, is that the Reykjavik, Iceland-based company aims to obtain regulatory approvals for multiple products almost simultaneously in multiple countries and then launch.

The worldwide market for biologic originator drugs exceeds $300 billion and is growing at a 10% clip each year. “We’re in the earlier stages of a long-term expansion for the global biosimilars market,” he said in a recent presentation on the company’s expansion strategy and the challenges of entering markets with different regulatory standards for biosimilar approval.

On November 24, 2020, Alvotech announced a 

 with CCHT Biopharmaceutical of Changchun, China, and Yangtze River Pharmaceutical Group, of Taizhou, China, to commercialize 8 biosimilars in China. The deal follows on the heels of other announced partnerships for distribution in North America, South America, Europe, the South Pacific, Africa, and the Middle East. Alvotech has biosimilars in development for autoimmune diseases, ophthalmology, and oncology.

Regulatory standards differ from country to country. While regulators in Europe and the United States tend to hold that comparative clinical efficacy trials are not of significant value in demonstrating biosimilarity, this is not the case elsewhere, where animal and in-human studies of biosimilars may be required to complete the package of evidence required for consideration of approval.

Analytical, pharmacokinetic (PK) studies are the foundation of biosimilar approvals in the United States, but when it comes to clinical studies—although they already were performed for originator drugs—the goal for some regulatory authorities may be an added level of reassurance, McClellan said.

“In vitro tests for looking at function are much more sensitive, and as you progress from binding assays and cell binding assays, and function cell assays, your sensitivity decreases for demonstrating similarity," he said. "Of course, as you move into in vivo animal models and human clinical trials, the clinical relevance is deemed to be more significant. It’s that balance. If you’re going to do an in vivo animal model, what are you trying to solve there. It’s likely it’s about providing the confidence about the safety of the molecule."

China tends to require animal studies as a condition of doing human clinical studies, as well as the use of locally sourced reference product for the comparator drugs. It would be easier if the reference product required for testing could be standardized across the globe, McClelland said. “How do you include China when you want to use 1 product for your clinical studies, whether PK or a comparative patient study? It’s an interesting challenge.”

Such requirements also make it difficult for Alvotech to execute on another of its strategic goals, which is to perform PK similarity and clinical confirmatory studies almost in parallel to one another to speed up development and get to regulatory approval faster. With regional partnerships across the globe, “We also have that commitment to ensure that we can develop our biosimilars in a speedy manner,” McClellan said.

China is very strict about requiring that nonclinical studies be performed before clinical studies, he added.

Smoothing out the obstacles in this quest means that Alvotech has to engage with regulatory authorities from individual countries early in the development process to shape the biosimilar development project and understand local priorities for approval, McClellan said.

Japan, also one of the world’s largest markets for biologics, presents a different challenge. That country’s regulatory authority requires that subjects of Japanese origin be included in clinical studies.

Another Alvotech goal is to develop commercial scale operations for its product development efforts. The company seeks to develop biosimilars for approvals in all indications of the reference products in the markets it enters.

At its headquarters in Reykjavik, Alvotech has a 140,000-square-foot facility for manufacturing and product development. It also has a production center under construction in Changchun that will have the capacity for producing 2.5 million “patient treatments” a year. The project is a partnership with the Changchun High & New Technology Industry Group.

The company has research and development operations in Julich and Hanover, Germany; Virginia; and Zurich, Switzerland.

Articles

Festival of Biologics Basel

Joseph E. McClellan, PhD, MBA, discussed navigation of regulatory hurdles as the company continues its quest to line up distribution partnership deals across the globe. 

Alvotech Scientific Officer Describes Company's Global Biosimilars Strategy

Investigators at the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine hope to reproduce results of a successful phase 2B trial of GP2 peptide/G-CSF in patients with HER2-equivocal or -positive breast cancer who have received a standard course of trastuzumab, reference or biosimilar form, following surgery.

GP2 plus GM-CSF is believed to stimulate a tumor-specific cytotoxic immune system response against HER2-positive cancer cells. Phase 2 studies help determine whether a drug shows any activity against the target disease and assist with setting optimal dosing. Phase 3 trials assess the value of a drug in a clinical setting.

In the retrospective, placebo-controlled phase 2B trial, completed in 2018, after a median 5 years of follow-up, no cancer recurrences were observed in the adjuvant setting among patients with HER2-equivocal or -positive breast cancer who received the full course of 6 primary intradermal injections over the initial 6 months (

 = .0338), according to subgroup analysis.

In that earlier study, the immune response, as measured by local skin tests and immunological assays, was potent, investigators said. In addition, among 138 patients who have received GP2 over 4 clinical trials, the treatment was well tolerated, with no serious adverse events attributable to the therapy, investigators said.

In the phase 3 trial, investigators hope to reproduce those results in preventing recurrence of HER2-equivocal or -positive breast cancer both post surgery and following an initial year of treatment with trastuzumab, including biosimilars.

GP2 is an investigational drug being developed by Greenwich LifeSciences of Stafford, Texas. Lead investigator and Greenwich LifeSciences CEO Snehal Patel pointed to the value of GP2 if it proves to be a reliable tool in reducing HER2-positive breast cancer recurrence. “We are addressing a potential market of up to $5 billion in a disease that affects 1 in 8 women, who if recur, will likely face metastatic breast cancer,” he said.

Patel SS, McWilliams DB, Fischette CT, et al. A prospective, randomized, multicenter, double-blinded, placebo-controlled phase III trial of the HER2/neupeptide GP2 + GM-CSF versus bacteriostatic saline/WFI placebo as adjuvant therapy after any trastuzumab-based therapy in HER2-positive women with operable breast cancer. Presented at: 2020 San Antonio Breast Cancer Symposium; December 8-11, 2020. Abstract OT-13-03. https://www.sabcs.org/Portals/SABCS2016/2020%20SABCS/Final%20PDF%20Docs%20111620_All%20PDF%20File%20No%20Embargoed%20Abstracts.pdf?ver=2020-11-17-095626-250

San Antonio Breast Cancer Symposium

GP2 peptide/G-CSF in HER2-equivocal and -positive breast cancer has shown promise.

Investigators Look to Cut Breast Cancer Recurrence With Posttrastuzumab Therapy

Bevacizumab biosimilar (Byvasda) in combination with the PD-1 inhibitor sintilimab injection (Tyvyt) has demonstrated significantly 

overall survival (OS) vs sorafenib (Nexavar) as frontline therapy in a phase 3 trial of patients with advanced unresectable hepatocellular carcinoma (HCC).

Based on the success of the randomized, open-label, multicenter ORIENT-32 trial (N = 571), Suzhou, China–based Innovent Biologics said it intends to apply to China’s National Medical Products Administration for approval of the drug combination.

“We look forward to this potentially becoming a new treatment regimen that could help more patients with HCC to live longer without their disease worsening,” said Hui Zhou, MD, vice president and head of Oncology Strategy and Medical Sciences for Innovent.

Byvasda is a recombinant humanized anti–vascular endothelial growth factor monoclonal antibody developed by Innovent and 

by the NMPA in June 2020. Tyvyt was codeveloped by Innovent and Lilly.

Interim findings also showed significantly improved progression-free survival (PFS) for the biosimilar combination. Findings from ORIENT-32 were presented at the European Society of Medical Oncology ASIA Virtual Congress 2020.

Compared with sorafenib, sintilimab injection with bevacizumab biosimilar demonstrated a 43.1% decreased risk of all-cause mortality (HR, 0.569; 95% CI, 0.431-0.751; 

 < .0001). Median OS was not reached in the combination arm vs 10.4 months for the sorafenib cohort, according to the independent data monitoring committee analysis.

Investigators said the combination therapy also showed a 43.5% decreased risk of progression (HR, 0.565; 95% CI, 0.455-0.701; 

 < .0001) by independent radiographic review committee analysis. Median PFS was 4.6 months in the combination arm vs 2.8 months in the sorafenib arm.

Investigators said the benefits of the combination therapy were consistent across all subgroups with no new safety signals. “With these results, Tyvyt plus Byvasda could potentially provide a new option for the first-line treatment of patients with advanced HCC,” investigators said.

“HCC is the fourth most common malignancy with the second highest mortality rate. More than half of new and fatal cases of HCC in the world occur in China every year,” said Zhou. “We are very pleased to see that the ORIENT-32 study demonstrated significant prolongation of OS and PFS in advanced HCC patients in China.”

ESMO ASIA Virtual Congress 2020

Bevacizuamb biosimilar in combination with sintilimab delivered significantly improved overall survival vs sorafenib. 

Innovent Biologics Biosimilar Combination Surpasses Sorafenib in ORIENT-32

 name suffixes are intended to aid in tracking these medicines and improve ability among health care providers to distinguish between these and other medicines; however, a study indicates that providers and health care administrators may struggle to find utility in these 4-letter appellations.

Biosimilar suffixes take the form of random jumbles of letters—deliberately devoid of meaning—such as “awwb,” which is tacked onto the end of the Amgen version of bevacizumab (bevacizumab-awwb, Mvasi). In a study presented at the American College of Rheumatology (ACR) Convergence 2020, investigators set out to evaluate how much providers and administrators know about biosimilars and whether they perceive the 

 as adding utility and reliability to the prescribing process.

Investigators said they found great variation in how well those surveyed understood basic concepts about biosimilars and a lack of appreciation for the suffix naming convention. “These survey findings suggest a knowledge gap with regard to biosimilars and lack of consensus about the usefulness of employing the 4-letter character suffix in clinical practice,” the authors wrote.

The survey included 83 prescribers and health care administrators such as pharmacists, nurses, and medical coders, an 18% response rate. Surveys were sent to individuals at the University of Pennsylvania Health System and the Corporal Michael J. Crescenz Veterans Affairs Medical Center, both in the Philadelphia area. Providers received a survey if they had previously prescribed a biosimilar.

Investigators said the general knowledge of biosimilars was “rather poor.” Just 52% (28) of respondents were able to answer correctly whether a biosimilar differed from a generic medicine (it does). And although suffixes are intended to help improve pharmacovigilance, 67% of respondents indicated that they used the brand name of the biosimilar in clinical practice to distinguish between biosimilars and their reference products. “Only a minority of respondents [27%] reported regular use of the 4-letter suffix to identify biologic therapies,” the authors wrote.

According to the findings, 85% overall said they find it easier to remember the brand name of a biosimilar than its nonproprietary name and suffix.

Among prescribers, 77% (51) answered correctly that a biosimilar has comparable efficacy, safety, and immunogenicity compared with an originator product. Among administrators, 94% (16) got the question right.

The survey results indicated 42% (28) of providers answered correctly that biosimilars are not generics, vs 88% (15) of administrators. And when it comes to knowing that, by regulatory standard, biosimilars must have the same (“exact”) amino acid sequence as the originator product, 32% (21) and 29% (5) of prescribers and administrators, respectively, answered correctly.

Investigators said 52% (34) of prescribers and 53% (9) of administrators answered correctly that there is variation between manufactured product batches whether they are originators or biosimilars.

“We hypothesize that lack of overall familiarity with biosimilars may have contributed to less comfort with the naming convention,” investigators wrote.

According to the survey, 32% of providers said they feel that the use of brand names for biosimilars introduces commercial bias in clinical decisions. And 21% of providers said the 4-letter suffix induces patients to believe there are “important differences” between biosimilars and originator products. Investigators said 32% of prescribers and 57% of administrators responded that suffixes cause inefficiencies because they conflict with other naming systems.

Of responders who said they were “still in training,” 27 (93%) were residents or fellows.

by Nancy Globus, PharmD, vice president of Regulatory Affairs at the Accreditation Council for Medical Affairs, examines some of the issues behind biosimilar suffixes.

Lavery C, Olave M, Leonard C, et al. Knowledge of biosimilars and perceptions of biosimilar naming conventions in clinical practice. Presented at: ACR Convergence 2020; November 5-9, 2020. Abstract 1605.

ACR Convergence 2020

The FDA naming convention and its utility are not well understood, and “poor” biosimilar knowledge may be partly to blame, investigators report.

Survey: Providers, Admins Struggle to Appreciate Biosimilar Suffixes

Two biosimilars were approved by the FDA in mid-2020, well down from the total of 10 approved last year, but this drop-off does not give a true account of the federal government’s commitment to expanding biosimilar options for patients, according to 

, JD, MBA, formerly a senior advisor to HHS and principal deputy director of the Center for Medicare at CMS.

At the Association for Accessible Medicines 2020 GRx+Biosims conference, Brooks, currently a consultant with South Capitol, discussed the federal policy and regulatory infrastructure for biosimilars that has been constructed over the past few years and pending changes that could pick up the pace of biosimilar adoption.

“Regardless of administration, regardless of party, everybody agrees that encouraging biosimilar uptake, encouraging more competition, is the direction we should be headed. That’s for a pretty obvious reason,” he said giving the oft-cited statistic that biologics, costly by nature, now represent 3% of prescriptions written and 40% or more of total drug costs. “Everyone agrees that the biosimilar market is critical to making sure patients are adequately cared for and we get a good return on our health care investment.”

Politicians may be prodded by public sentiment to beef up biosimilar adoption, but the commitment to getting this done extends deep into the professional ranks of the FDA, CMS, and other federal departments, Brooks said. Such consensus led to the FDA’s Biosimilar Action Plan in July 2018, which was supported by President Donald Trump’s drug price reduction “blueprint,” issued in May 2018.

“Encouraging biosimilar competition was one of the primary planks identified as important for reducing costs and improving quality,” he said. “We saw a lot of actions from both the FDA/regulatory side in terms of governing the supply of biosimilars coming into the marketplace, as well as on the CMS side in terms of how we reimburse.”

for the interchangeable biosimilar pathway. This would take the doctor decision out of whether biosimilars or originator drugs are issued at the pharmacy counter. Interchangeability qualification is a stringent pathway for these agents and that’s because the FDA is very concerned about maintaining safety standards, Brooks said. But there are companies that are moving insulins through the pipeline, which could be the first interchangeable biosimilars, supported by recent FDA “patch” guidance that facilitates the process. This included modification of the requirements for immunogenicity studies leading to biosimilar approval. Interchangeable insulins could become a reality within a 24- or 36-month timeframe, “which would be a tremendous win for a lot of patients as well as for our overall health care system,” he said.

An example of a building block that levels the playing field for biosimilars is the 

, which was signed into law in December 2019 and targeted anticompetitive practices that make it difficult for biosimilar companies to obtain reference product samples they need for development of biosimilars.

Revisions to guidance on naming biosimilars (March 2019) have relaxed but not eliminated requirements for 4-letter random suffixes on biosimilar names, which critics say differentiate biosimilars from reference products in patients’ minds and make it harder for these drugs to achieve acceptance. “That guidance does not come as far as some stakeholders in the industry would like, but the FDA has also engaged in a pretty comprehensive education campaign to reassure people around the safety of biosimilars,” Brooks said. “As we saw with generics, where it took 5, 10, 15 years to get everybody on board with assurances around the safety of those products, there’ll be a journey here.”

On the payment side, CMS has assigned separate codes for each biosimilar “so that each company entering the biosimilar space can control a little bit more of their destiny in terms of what their [average sales price] is going to look like, what their pricing strategy is going to be,” he said.

Proposed changes to Medicare Part D would lower cost sharing for patients who use drugs on a 

designed to incentivize manufacturers to compete to get their drugs on this tier by offering lower prices. “It hasn’t been finalized yet; we’re still anxiously keeping our eyes on the Federal Register to see if CMS will finalize that policy—hopefully, sometime this fall—but it is a particularly good step forward, and it’s also an indication of how the agency is looking at this issue. They see biosimilars as a really important tool in terms of improving the cost piece,” Brooks said.

This tier might also encourage more biosimilar developers to enter the market, thereby enhancing competition, he said.

Several further ideas under consideration at CMS also could make a difference, Brooks said. One is the creation of a demonstration model for shared savings from biosimilars, under which providers would be “nudged” to use biosimilars in place of reference products because of the additional revenue they might earn.

He also expressed faith in the potential value of a Star Ratings system of measures that would grade Medicare Advantage plans on their biosimilar uptake and incentivize a greater shift in that direction. “There are a lot of exciting policy ideas out there. This an extremely dynamic marketplace,” Brooks concluded.

AAM GRx+Biosims

Prior to the turmoil of the pandemic, the FDA and CMS were at work on shoring up the biosimilars market, and this work continues on various fronts, a regulatory/policy expert explains.

Fed Expert Describes Improving Regulatory, Policy Structure for Biosimilars

Several legislative initiatives supporting biosimilar use are active in Congress, and the encouraging part is that many have bipartisan backing, said Molly Burich, associate director for Public Policy at Boehringer Ingelheim Pharmaceuticals, who provided her take on the health of the biosimilars market at the Association for Accessible Medicines GRx+Biosims 2020 conference.

“We’re definitely seeing some good tailwinds on biosimilars, but I would caution everyone that we aren’t there yet. This is still a very nascent market, and while the oncology market is certainly showing us reasons to be optimistic, the immunology market is still trailing,” Burich said in her discussion.

“We have to make sure that we’re setting up a system—whether that’s a combination of regulatory administration activities and potential legislative goals—that is not only moving across all therapeutic areas, but also creating a sustainable, long-term biosimilar market,” she said.

Burich highlighted various pieces of legislation that she said would incentivize the use of biosimilars by stimulating providers, patients, and payers to push these lower-cost products into centerfield.

, also known as the ACCESS for Biosimilars Act, would eliminate patient cost shares for biosimilars provided under Medicare Part B and drive biosimilar uptake from the patient direction. “It could serve as an incentive to get patients talking to their physician about these options,” Burich said. “While the majority of beneficiaries of Medicare Part B do have wraparound coverage that helps with the 20% coinsurance, there are a chunk of patients who do not, and so this bill would either lower their cost shares significantly or zero [the cost shares] out if, in fact, they’re given the biosimilar.”

 would increase provider payments for use of biosimilars to average sales price plus 8%, up from plus 6%, Burich noted. Under the wording of the bill, this increased payment opportunity would extend for 5 years.

Another potentially useful stimulus for biosimilar circulation is 

, Burich said. This bill would augment the Star Rating measures used to grade Medicare Advantage coverage plans. Star Ratings guide patients in their choice of plans, and the higher the ratings, presumably, the more patients select these plans. The measures under consideration for biosimilar stimulus include the following assessments:

whether a biosimilar is included on plan formulary in lieu of or in addition to its reference biologic

tier placement or cost sharing for a biosimilar vs reference product

how and whether tools for utilization management are used for a biosimilar vs reference product

the percentage of plan enrollees who are prescribed a biosimilar vs its reference product

, the Purple Book Continuity Act, is a piece of legislation that would raise the Purple Book of patent information to a more practical level so that biosimilar developers are better equipped to anticipate the obstacles they’ll encounter in trying to bring their products to market, Burich noted.

“There has been a lot of talk that the Purple Book isn’t set up exactly the same way as the Orange Book [for generic medicines], so is there a way to take some of the provisions in the Orange Book around patents and other really important information that impacts a developer’s decision around that product and put that in the Purple Book?” 

 is a federal appropriations bill that contains language encouraging greater utilization of biosimilars in Medicare Part B, she said. Related to this, the House Appropriations Committee has encouraged the administration to support new policies for reducing patient co-pays and developing cost-sharing models to spur biosimilar uptake.

 would require HHS to maintain a website and perform other activities to educate providers, patients, and other stakeholders about the value and importance of biosimilars.

“There’s definitely progress being made, and I don’t want to undersell that progress. But the reality is, we still have a ways to go, and we need to be looking at the incentives that will get us a little closer to biosimilar success,” Burich said.

The good news is the bipartisan consensus that these drugs can contribute to broader access and health care system savings and deserve a fighting chance, Burich said. “The focus on drug pricing, the focus on patient affordability, government spending—all of these things—they’re not going to go away.”

Despite a rocky power transition at the federal level, the compass heading for biosimilars is unchanged, said policy expert Molly Burich.  

Burich: Saving Grace for Biosimilars in 2021 Will Be Bipartisan Support 

A study of multiple biosimilar switches for patients with a variety of rheumatic musculoskeletal diseases (RMDs) demonstrated a high rate of patient retention (89%) and no major changes in disease activity or function, investigators reported at the American College of Rheumatology Convergence 2020 meeting. 

Sufficient information is available to elucidate the safety and efficacy of a single switch from an originator to a biosimilar product in the treatment of RMDs, but “The effect of multiple switching between biosimilars of the same reference product has not been thoroughly investigated to date,” investigators said.

Biosimilars are available at significant discounts to reference products, and the more biosimilars that are available, the more attractive multiple switching becomes, as providers and patients look for the most affordable treatment; hence, the significance of the study, investigators said.

The retrospective study enrolled 100 patients with rheumatoid arthritis (n = 54), axial spondyloarthritis (n = 27), and psoriatic arthritis (n = 19) who switched to 2 etanercept biosimilars for economic reasons over a 21.1-month average follow-up period. The switches (first, Benepali, SB4; second, Erelzi, GP2015) included in the study began in 2017, and the end of the observation period was October 2019.

Disease activity, function, and adverse events (AEs) were assessed regularly, and the primary end point was scores documented at week 12 after the second switch. The composite Disease Activity Score-28 and the Stanford Health Assessment Questionnaire Disability Index were used to measure changes in rheumatoid arthritis and psoriatic arthritis. Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and Ankylosing Spondylitis Disease Activity Score were used for axial spondyloarthritis.

The 89% retention rate was observed about 6 months after the second switch. Seven patients discontinued due to inefficacy or AEs, 2 were lost to follow-up, and 1 patient died (cardiac arrest).

Investigators said 14 AEs were reported in 8 patients; and among those patients, 4 resumed treatment with reference etanercept in month 6; one patient was successfully retreated with Erelzi in month 3 after experiencing mucosal erosions; and 3 patients were switched to other forms of medication. Week 12 scores for disease activity and function were unchanged.

Investigators said their study is valuable because biosimilar switching is likely to increase for economic reasons. 

High Patient Retention Observed for Multiple Etanercept Switches

In a study of use of infliximab biosimilars among patients with gastrointestinal and rheumatologic conditions, investigators found high adherence.

The retrospective study, presented at the American College of Rheumatology (ACR) annual meeting, involved 533 patients in the IBM MarketScan commercial insurance database who were treated with infliximab from 2014 to 2018. Investigators characterized those who initiated use of infliximab biosimilars after treatment with the reference product or no prior infliximab treatment.

Patients were divided according to never having used infliximab reference product, early switchers with less than 2 years of reference product use, and late switchers with greater than 2 years of reference product use.

Investigators said 41.6% to 47.4% of patients had inflammatory bowel disease and 34.2% to 48.7% had rheumatoid arthritis. Psoriasis patients accounted for 8.8% to 14.2% of the population.

Roughly half of patients were highly adherent to infliximab biosimilars at 12 months of treatment with these alternative agents. Among those with ≥ 12 months of follow-up care, 53.6% of naïve users, 44.3% of early switchers, and 56.1% of late switchers remained highly adherent at 12 months.

High adherence among patients with at least 18 months of follow-up amounted to 59.3% for naïve infliximab biosimilar users, 50% for early switchers, and 40.7% for late switchers.

Investigators found that there was no significant difference in adherence among those who initiated biosimilar infliximab.

Investigators divided comorbidity rates according to patient type. Among infliximab naïve users, 14.3% had diabetes; 42.9%, hypertension; 17.3%, depression; chronic obstructive pulmonary disease, 19.4%; and cancer, 11.2%.

The respective percentages for early switchers were 17.5%, 37.7%, 21.1%, 7%, and 3.5%; and for late switchers, 15.9%, 38.1%, 10.6%, 15.9%, and 11.5%.

The adjusted odds ratio for high adherence among naïve infliximab biosimilar users was 1.68 (

 = .35), meaning the former group was far more likely to adhere to infliximab biosimilar than the latter group.

Sarvesh S, Alanaeme JC, Curtis JR, Yun H. Utilization and adherence among infliximab biosimilar initiators in a U.S. national commercial insurance database. Presented at: ACR Convergence 2020; November 5-9, 2020. Poster 0555.

Investigators looked at adherence in patients who switched from reference infliximab during treatment for rheumatologic and gastrointestinal treatment. 

High Adherence Noted Among Infliximab Biosimilar Users

The coronavirus disease 2019 (COVID-19) pandemic has stretched health care systems but may also create room for improving utilization of biosimilars, according to a presentation at the Terrapinn Festival of Biologics Basel 2020. 

“Interestingly, for 2020, this crisis is also the greatest opportunity we have to rethink, rebuild, and reshape. We have a new normal to face, and I think that's what we need to consider,” said Julie Maréchal-Jamil, director of Biosimilar Policy & Science at Medicines for Europe and an advisory board member for The Center for Biosimilars®.

In the presentation, Maréchal-Jamil discussed what steps need to be taken to develop policies that will foster sustainable access to the biosimilars market for patients and allow European health care systems to get the greatest benefit from biosimilar use.

She laid out 3 things that regulators should consider to achieve these goals, including developing a vision where savings are reinvested into measures that improve health by improving access for patients; targeting policy frameworks to individual countries; and incorporating components to make sure the policies function efficiently.​ 

A vision for health involves addressing health and access needs by developing roadmaps to achieve objectives, which is what France and the United Kingdom have done, explained Maréchal-Jamil.

She said the United Kingdom implemented a policy to expand access to off-patent biologics. The policy allows for reference products to compete alongside biosimilars for market access, meaning that patients exclusively use whatever product is deemed to be the “best value biologic.”

According to Maréchal-Jamil, in the United Kingdom, targets for adoption of the best value biologic are 90% for new patients within 3 months of a biosimilar launch and 80% for existing patients within 12 months.

The French implemented a policy to increase the development of innovative biologics by encouraging that 80% of existing patients transition to a biosimilar by 2022. The French theorize this would encourage innovator companies to develop new medicines once they lose patent protection for older ones.

Maréchal-Jamil said Norway and Poland also have unique strategies for how they increase biosimilar utilization.

In Norway, biosimilars were widely used in the hospital setting but rarely used in the community pharmacy setting. Maréchal-Jamil said Norway had reflect on how to adjust its framework to achieve mass use.

Maréchal-Jamil also said the Poland’s baseline biosimilar access rate is lower than the average for the European Union despite having good use rates for some biosimilars, suggesting that reforming drug programs or imposing budget caps would be more effective in addressing biosimilar use than implementing biosimilar regulatory policies.

Additionally, Maréchal-Jamil said that originators that are expected to lose patent exclusivities in the future will require policy adjustments and new policies to be added over time.

Maréchal-Jamil said that successful policy changes must build awareness, trust, and confidence, drive biosimilar use, and translate cost efficiency gains to better health.

To increase awareness, trust, and confidence in biosimilars, Maréchal-Jamil suggested that easy-to-understand educational information must be given and made continuously available to the public. Additionally, trust can be built by continuously involving stakeholders in policymaking.

According to Maréchal-Jamil, nearly half of medicines agencies in Europe still do not have biosimilar educational resources listed on their websites, even though Europe as a whole has 20 years of experience using biosimilars.

Maréchal-Jamil said that studying what other countries have done could inspire policies that drive biosimilar use. Maréchal-Jamil mentioned that IQVIA’s country 

 published in June would be a good source of inspiration because they detail the policies of 12 European countries regarding biosimilar switching, tender systems, utilization incentives, and pricing regulations.

Lastly, Maréchal-Jamil mentioned Germany as an example of how to translate cost efficiency to impact treatment access to biologics. The Bavaria study on treatments for rheumatoid arthritis found that the introduction of biosimilar competition to the market decreased the amount of time before a patient could get access from 7.4 years to just 4 months, suggesting competition can play a major role in increasing access for patients.

In Europe, the pandemic has revealed problems within health care systems and the need to increase access to biosimilars and reform health care policies.



Prioritize Biosimilar Uptake in Europe, Conference Speaker Says

In a keynote speech to a generic and biosimilar drug industry group, Alex M. Azar, secretary of HHS, gave a pat on the back to outgoing President Donald Trump, praising his policies and executive orders aimed at reducing prescription drug costs.

In addition, accelerated approvals of biosimilars and generic drugs combined with growing market competition since 2017 have contributed to a plateau in drug price inflation the past several years, Azar said at the Association for Accessible Medicine (AAM) GRx+Biosims virtual conference.

He attributed this trend not to pricing restraint on the part of manufacturers but, specifically, to market dynamics and drug policies promoted by Trump.

“Since we released the president’s drug pricing ‘

’ in May 2018, the official government measurement of drug price inflation has been flat. That measure saw the largest drop in nearly 50 years from June 2018 to June 2019. Now, I don’t think that’s because of the goodness of drug companies’ hearts. In fact, I worked at a drug company myself, and I can more or less assure you it’s not. In significant part, it’s because of the market discipline that your companies provide,” Azar said.

study published earlier this year indicate list prices for prescription drugs climbed sharply from the start of the Trump administration through 2018, but net drug prices increased much more moderately during those years, according to the study. The study did not describe drug price behavior after 2018.

“I believe we’ve seen more efforts to promote competition in prescription drug markets from HHS and our colleagues at FDA than we’ve seen since the passage of Hatch-Waxman in the 1980s,” Azar said. The Hatch-Waxman Act (1984) encouraged the manufacture of generic drugs and created a regulatory system for these agents.

“We’ve set records for approvals of generic drugs in 2017 [937], 2018 [971], and 2019 [1171], while also accelerating approvals of biosimilars. The savings that these drugs deliver are massive,” Azar said. There were 10 biosimilar approvals in 2019, a record number, but just 2 so far in 2020.

There are roughly 90 ongoing biosimilar development projects on file with the FDA, which has not officially given any explanation for the reduced number of approvals this year, although in general remarks FDA officials have stated that efforts to approve trials and review treatments related to coronavirus disease 2019 have required a massive shift of priorities and resources.

Generic drug savings totaled $313 billion in 2019, $96.1 billion of that for the Medicare program and $48.5 billion under Medicaid, Azar said, quoting from a 2020 

. “We’ve also taken steps to drive not just faster generic and biosimilar approvals but also faster adoption of these options, and we’ve allowed Part D plans to accelerate substitutions of generic drugs for brand drugs, and we’ve given Medicare Advantage plans new tools to negotiate lower prices that they’ve already used to substitute lower cost biosimilars.”

Azar said a 2018 HHS report identified $3 billion in potential savings on $9 billion that Medicare Part D plans are spending annually on name brand drugs that have generic alternatives. Achieving those savings involves eliminating “kickbacks” to middlemen in the drug supply chain and fixing the “broken rebate system” that rewards payers and pharmacy benefit managers for preferring certain drugs, whether or not they are lowest cost, he said.

“We’re also working to propose rules around Part B drugs that have the potential to be equally significant for American drug costs, especially with regard to rapidly rising expenditures on biologics, which today represent almost 40% of prescription drug spending,” Azar said.

He said biosimilar uptake in the health care marketplace has been “slower than we’d like, in part because the Part B system actually encourages prescribing more expensive options. If we can bring to the biologics market just a fraction of the savings that generic drugs have brought to American patients, that will be a transformative shift.”

Hernandez I, San-Juan-Rodriguez A, Good CB, et al. Changes in list prices, net prices, and discounts for branded drugs in the US, 2007-2018. 

. 2020;323(9):854-862. doi:10.1001/jama.2020.1012

HHS Secretary Alex M. Azar said efforts and policies to counter a sharply upward drug price trend have been successful, in a talk with the Association for Accessible Medicine.

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