Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

The problem of slow biosimilar uptake is not unique to the United States. The Emerald Isle is suffering the lack of these agents, 

The group has called upon Republic of Ireland Minister for Health Stephen Donnelly to bring about a change in legislation that would enable pharmacists to fill prescriptions with lower-cost biosimilars instead of originator brands, calling a policy such as this “the fastest and most effective way to ensure a rapid and meaningful increase in the use of biosimilars.”

The IPU has estimated that Ireland has missed out on $439 million in potential biosimilar savings since 2017.  

Currently, the Health Products Regulatory Authority (HPRA) allows European Medicines Agency (EMA)-approved biosimilars to be used interchangeably with originator products “under supervision of a physician.”

The HPRA allows patients receiving originator products to be switched to biosimilars “should a prescribing physician wish to do so.”

 confirmatory clinical studies for every indication of a biosimilar if the reference product it copies has already been approved for those indications. This has enabled physicians to “extrapolate,” or use biosimilars for reference product—approved indications.

Eoghan Hanly, vice president of the IPU, said his group demonstrated the potential savings from biosimilars in a study done 3 years ago. He said the time is right for health authorities to become aggressive about removing barriers to biosimilar adoption. “The finances of the health service have never been in great shape, and the ongoing pandemic will only make that worse,” he said.

The lost savings have already been costly to the health of the population of Ireland, he added. “We are not able to use that money to support people in our health service today, because that opportunity was wasted. Will we be back here again saying the same thing in another 3 years?”

Health authorities in Ireland have also seen 

 from other industry groups to bring biosimilars to bear on the medicine affordability issue. Medicines for Ireland, which represents generic pharmaceutical manufacturers, including biosimilars developers, in 2018 also said that Ireland was missing out on potential savings, but presented a substantially lower figure than that put forth by the IPU. Medicines for Ireland said Ireland's national health system was missing out on $29 million in annual savings. The group said that whereas biosimilar adoption is rising across Europe, in Ireland, usage has hovered at basement levels. Just 2% of the market demand for biologics was filled by biosimilars as of January 2018, it said.

Currently, biosimilars account for just 10% of the market in Ireland for biological medicines, Hanly said.

Instead, biosimilars should be following the example of generics, which since 2013 have increased from 17% to over 40% of the market for small molecule drugs, saving an estimated $1.4 billion, Hanly said. In the United States, by contrast, generic medicines represent 90% or more of traditional medicines (nonbiologics) sold, and laws vary from state to state on generic substitution. Some drugs 

Estimates vary on the degree of biosimilar penetration in the US market. According to Juliana Reed, a vice president and Global Corporate Affairs lead for Pfizer, biosimilars 

 just 2.3% of the US biologics marketplace.

“As the experience of generic substitution demonstrated, allowing community pharmacists to substitute is the fastest and most effective way to ensure a rapid and meaningful increase in the usage of biosimilars,” the IPU said.

“An amendment to the Health Pricing and Supply of Medical Goods Act 2013 would allow pharmacists to substitute a biological reference product with a biosimilar, and the IPU is now calling on Donnelly to legislate for this. Every week that the government fails to implement this proposal is costing roughly [$2.4 million] in potential savings foregone,” Hanly said.

 of biosimilars, and in many countries in the European Union, these drugs are used aggressively, leading to substantial reductions in the use of originator drugs that have lost patent protections.

Articles

Pharmacists in Ireland say the country is losing out on hundreds of millions of dollars in savings owing to the absence of a biosimilar substitution policy.

Irish Pharmacists Lobby for Biosimilar Substitution

Shanghai Henlius Biotech reached another regulatory milestone as China’s National Medical Products Administration (NMPA) 

 its trastuzumab biosimilar (HLX02; Zercepac [European name]) for marketing.

 by the European Commission. These regulatory nods make HLX02 the first monoclonal antibody developed in China to be approved in both China and the European Union.

The biosimilar is indicated for the treatment of 

-postive metastatic gastric cancer. These indications correspond to the approved indications in China for the trastuzumab originator product, which has been included on China’s National Reimbursement Drug List since 2017.

Henlius said that results from analytical studies, preclinical studies, a phase 1 clinical study, and a global multicenter phase 3 clinical study demonstrated that HLX02 “is highly similar to the reference trastuzumab in terms of quality, safety and efficacy.”

“The approval of HLX02 will improve the accessibility of trastuzumab in China and further strengthen the standardized treatment of patients with HER2-positive breast and gastric cancer," said Binghe Xu, principal investigator of the phase 3 study.

Wenjie Zhang, president of Henlius, said HLX02 marks the second of the company’s products approved for launch. The first was a rituximab biosimilar (HLX01), 

 in China and marking that country’s first approved biosimilar. The approval for this drug, used in oncology and for autoimmune diseases, came in February 2019.

In April, the company announced that its new drug application for a denosumab biosimilar was 

 for review by the NMPA. The drug is intended for the osteoporosis market.

Up-and-coming Henlius Biotech consolidates its footing in the biosimilar world with another regulatory approval.

China Approves Henlius' Biosimilar Trastuzumab

The top 10 biologics by revenue have all been on the market more than 17 years, and each has amassed cumulative sales of more than $40 billion since launch. Those include adalimumab (Humira, $112 billion), epoetin alpha (Epogen, $97 billion), and etanercept (Enbrel, $80 billion). However, biosimilars for these drugs have yet to achieve more than a toehold in the US marketplace, and for employers, this represents a huge missed opportunity, according to Juliana Reed, MS, a vice president and Global Corporate Affairs lead for Pfizer.

“The big story is the low uptake of biosimilars in the United States. Cost savings is being left on the table,” she said in an employer issues webinar held this week hosted by the Pacific Business Group on Health and the Integrated Benefits Institute.

Reed noted that although 60% of overall biologic medicine sales occur in the United States, 90% of biosimilar sales occur in Europe, and she urged US employers to get involved and start advocating for greater use of biosimilars.

In the United States market, the “lost savings” amounts to $20.4 billion from 2018 to 2020, she said. “This is not just for Medicare. This is across the marketplace.”

“It’s going to take proactive work on your part,” she told employers, to funnel biosimilars into the health care stream and wrest some of those billions away from the dominant originator brands.

These unrealized savings could have reduced patients’ out-of-pocket expenses by $167.5 million in 2020, she said. “It’s something to think about especially considering that we are looking at recessionary conditions and negative economic impact from [the pandemic].”

Former FDA Commissioner Scott Gottlieb, MD, was a champion of biosimilars, and that momentum has not been lost with his departure, she said. There is support from the current administration and both sides of the aisle in Congress to move forward on driving down pharmaceutical costs. This is really about supporting the sustainability of the market, supporting the uptake, supporting the [biosimilar] competition so that we can drive lower cost,” she said.

There are lessons that can be learned from the market for generics, which received a big boost from the Hatch-Waxman Act of 1984. Provisions of that legislation spurred the development of generics while preserving incentives for innovator companies to develop new products. Hatch-Waxman kept the United States in the forefront of drug innovation but also enabled tremendous savings. Ninety percent of prescriptions filled in the United States are generics, and 95.3% of generic prescriptions are filled for $20 or less, Reed said, and that amounts to hundreds of billions in savings each year.

“What type of lessons could be applied in the biosimilars marketplace that could help grow the marketplace but also see success and continued sustainability of biosimilars?” Reed asked. One way is to incentivize biosimilar uptake, and that can be done by introducing policies that cut patient out-of-pocket costs, share savings with providers who prescribe biosimilars, and increase the average sales price add-on paid to physicians for biosimilar purchases.

A piece of legislation she said that would accomplish the add-on increase is S-2543, the 

, would target anticompetitive practices that biosimilar advocates say are rampant and that cause patients and providers to lose confidence in the safety and efficacy of biosimilars, although FDA approvals carry the assurance that biosimilars are as safe and efficacious as originator drugs.

“We know we have to address anticompetitive behaviors that disincentivize the uptake of biosimilars, but we also need proactive policies that incentivize the uptake of biosimilars," Reed said.

She added that anticompetitive practices may include deliberately disparaging statements and misinformation that sows confusion and doubt about these products. Other factors that impede biosimilar uptake and that need to be addressed include:

Exclusionary contracting and rebate practices

Failure to incorporate successful global experience with biosimilars

The often-long delays between FDA approval of a biosimilar and its launch

“Biologics right now represent the majority of the medicine marketplace here in the United States but also the majority of the spend,” which is why it’s important to focus on the opportunity available in biosimilars to reduce cost, Reed said.

Pfizer has made a commitment to the biosimilar space and during the first quarter of 2020 was among the 

Defining biosimilar use in the United States as "sluggish," Juliana Reed, MS, said employers have to get involved.

Pfizer Expert Urges Employers to Get Proactive on Biosimilars

Employers asserting their own desire to see biosimilars implemented among their employees was the theme of a Pacific Coast day of discussions involving representatives from Walt Disney, Costco, and CalPERS, the California Public Employees’ Retirement System.

The talks were sponsored by the Pacific Business Group on Health and the Integrated Benefits Institute. Employer health plan representatives discussed how they struggled to understand why biosimilar usage is so low and began putting the building blocks together to drive more patient use and greater savings.

Melissa Mantong, PharmD, MS, FCSHP, a pharmaceutical consultant at CalPERS, said the system went through a complex analysis stretching over 2 years during which it tried to decide the best way to implement a “biosimilar-first” program that would get these drugs into play.

CalPERS has 1.4 million members and spends $2.15 billion on drugs each year. Of that, $828 million is spent on specialty drugs, which include biosimilars, so the potential savings is vast.

Starting on January 1, 2021, the system plans to require that adult patients use an infliximab biosimilar first in preferred provider health plans. Currently, the originator infliximab, Remicade, has a 96.4% share of the market, with the remainder divided between the biosimilars Inflectra (3.2%) and Renflexis (0.4%), Mantong said, citing IQVIA data.

Getting to that step began in 2018, when CalPERS began analyzing data and discussing biosimilar goals with manufacturers. The company then talked with health plans about their biosimilar preferences. Barriers to biosimilar use that became evident included claims support issues and misalignment with health plan goals.

Those issues contributed to a decision to switch to implementing a biosimilar-first strategy with CalPERS’ pharmacy benefits manager. However, in the planning it was determined that the complexity of doing it this way was overwhelming and it was better to try increasing biosimilar use on the health plan medical benefit (specialty drug) side. The scope was limited to patients new to therapy and over the age of 18. The health plan was willing to go along and the plan appears to be on the approach path, Mantong said.

The most significant barriers encountered were aligning strategy with the health plan’s goals, limitations of the health plan system, and the complexity of medical benefits, she said. “If I had a magic wand, these are the limitations I would make go away,” she said.

“CalPERS is committed to supporting biosimilars, and we want to make sure biosimilars stay on the market to provide alternative price competition to the reference products,” she added.

Ladd Carmen, BPharm, director of specialty pharmacy services for Costco, said the discount, bulk retailer saw a need to drive higher use of biosimilars among its employees. Costco has 500 retail locations, each of which has a pharmacy, so it was well set up to implement such an initiative.

“We were really perplexed why these lower cost products weren’t being utilized more frequently,” Carmen said. He noted that the cost for Remicade was 30% higher than for biosimilars, “yet nearly 100% of our claims on the medical benefit remain for Remicade.”

That was counter to Cosco’s emphasis on competition and low prices, and Carmen said the company realized that if it didn’t intervene, it’d only be contributing to the use of higher-cost medicine despite the availability of lower-cost biosimilars. “It ultimately ends up costing us as an employer more.”

Negotiations between manufacturers and medical carriers play a large role in the continuing use of higher cost reference products, he noted. Also, “there can be a misalignment of incentives from the prescriber standpoint.”

When implementing a biosimilar plan, Costco decided to focus on infliximab to keep it simple. The company turned to its medical carrier to assess utilization patterns and how much could be saved with a switch to biosimilars. Costco officially launched a pilot biosimilar program on January 1, 2020.

As part of that, the company inserted a precertification requirement so that intervention was possible whenever a physician requested the originator product, Remicade. Use of the biosimilar was mandatory before the innovator product. Efforts were also made to ensure that patient coverage would be the same whether the product was covered on the medical benefit or pharmacy benefit side.

Bill Dinger, MBA, CPA, director of Healthcare Innovation & Labor Support for The Walt Disney Company, said the entertainment company is just getting started with a biosimilars program. It recognized the trend toward biosimilars but had to push a little to start things moving.

Disney has a small amount of biosimilar usage among its employees and when it investigated the potential for higher employment of these drugs, the typical answers the company got from its health partners were that biosimilars are still a far-off concept and putting them front and center was not a priority, Dinger said.

Disney health officials heard good things about biosimilars so they decided to “dig in a little bit further.” They also noted that a large amount of drug spending was driven by doctors’ offices and that it was very difficult to get clarity on that spending; and further, it was unclear whether providers had an incentive to switch to biosimilars. “There’s really none unless they’re on some form of contract,” Dinger said.

It also became clear that the pipeline of biosimilars was large and could replace a significant amount of the pharmaceuticals currently used by Disney employees at a savings.

Moving further into biosimilar use would require expertise and a cost justification with regard to the upfront investment, Dinger said.

The company had biosimilar manufacturers step forward with offers to partner, and Disney narrowed the initial field of biosimilars it would target. “We don’t want to get ourselves too far in until we get good at this, so how many drugs should we focus on? Right now we’re only looking at 4 or 5 [biosimilars], and honestly, the amount of savings from those 4 or 5 drugs more than justifies the investment we’ll be making—significantly exceeds the investment,” Dinger said.

The next question was how to drive patient volume to the infusion center. They found they had enough patient volume based on patient treatment at existing facilities and could engineer the change via referrals.

They decided to build a small infusion center at the Epcot theme park in Florida and “Disney-fy” it, Dinger said.

They made it convenient with “fast pass” scheduling to minimize time away from work, created a bright environment with lots of windows, comfortable seating, and Disney+ programs, wifi, and cable television options. “What we’re trying to do is take this process that is difficult and make it better. We’re also trying to drive some savings and align with our ‘whole person approach’ and hold everybody together,” Dinger said.

Dismayed at the low biosimilar uptake and the lost savings, large employers are taking matters into their own hands.
 

Disney Official, Others Talk About Switch to Biosimilars

Biosimilars have helped to transform the treatment of breast cancer in recent years, given that there are multiple trastuzumab biosimilars now available, according to Jacob Kettle, PharmD, BCOP, who led a recent discussion on the topic for 

Kettle, with the University of Missouri Health Care, Columbia, spoke with Allison Butts, PharmD, BCOP, of the University of Kentucky Markey Cancer Center in Lexington. They 

 payer policy and its influence on choice of biosimilars, along with concerns about use of biosimilars in place of originator drugs.

The Markey Cancer Center has been open to the use of biosimilars, Butts said, indicating that she feels comfortable substituting these products for reference trastuzumab and hasn’t noticed much “pushback” against biosimilars from the clinician community at Markey.

FDA standards for approval give her confidence in biosimilars, although Butts said she pays close attention to infusion reactions. “Infusion reactions are interesting when we’re talking about monoclonal [antibodies] because that’s certainly a concern with any [biosimilars] across the board. Does that rate of infusion reaction change or not?”

Biosimilars are more widely accepted as supportive care drugs, but in the oncology curative setting, there’s nervousness among physicians because the stakes are higher, Kettle noted. He asked Butts whether Markey clinicians experienced the same concerns about using trastuzumab biosimilars in the curative setting.

Butts replied there were no concerns. “They can show that it’s effectively targeting 

[positive breast cancer]. It’s effectively clearing out and leaving the body as it’s supposed to,” she said.

For his part, Kettle said that University of Missouri encounters difficulty employing and optimizing biosimilars amid multiple payer mandates that dictate which biosimilars may be used. “We have a lot of different payer mandates in the mix that preclude us from being able to drive the ship to what may be best for our own institution,” he said. “One payer may prefer product A for clinical, operational, and financial reasons—what have you. Another payer may like product B, and another may like product C.

“Half of patients are still on the originator product because they’ve been on it for 5 years, and we don’t want to disrupt them,” he said.

“That creates a nightmare scenario from [the perspective of] ordering, authorizations, and drug dispensing. To me, that is the bigger hurdle that we’ve encountered with biosimilars and how they play a role in cancer therapy,” he said.

University of Missouri Health Care finds these issues a challenge in getting the most out of biosimilars, Kettle said.

“That’s a great point,” Butts said. “You have to draw the line somewhere. You can’t have 10 trastuzumab products sitting in your refrigerator” because each payer requires something different.

 to find out how Emory Healthcare in Atlanta, Georgia, succeeded in getting physicians to incorporate use of biosimilars.

Pharmacy experts discuss their level of confidence with biosimilars and some of the hurdles that stand in the way of optimizing these lower-cost medicines.

At University of Missouri Health Care, Biosimilars Are Transformative but Somewhat Restricted

Japanese investigators hope to shed light on durability of clinical remission in rheumatoid arthritis (RA) following discontinuation of treatment with an infliximab biosimilar (CT-P13, Remsima).

“It is the next great issue whether disease activity can be maintained…after discontinuation of CT-P13, because no evidence is available” regarding the clinical outcome after biosimilar infliximab is stopped in RA, they wrote.

Rheumatoid arthritis is a chronic, systemic inflammatory disease that when uncontrolled can lead to joint destruction and deformity, lowering patients’ quality of life. Advances in the use of biologic disease modifying antirheumatic drugs, including biosimilars, have improved clinical outcomes, leading to low disease activity and clinical remission.

In the ongoing IFX-SIRIUS STUDY I, investigators are evaluating whether continued treatment with biosimilar infliximab is not inferior to treatment with the originator product in maintaining nonclinical relapse. The new study, 

, continues with the evaluation of what happens once treatment with the biosimilar is stopped.

The clinical findings will be important, the investigators note, because infliximab is a costly drug whether the originator or a biosimilar is used. Therefore, it is important to know if disease activity can be suppressed following discontinuation of the biosimilar in patients with RA.

Previous studies have suggested that the disease can be 

 following treatment cessation with antirheumatic drugs, so the investigators expect encouraging findings from IFX-SIRIUS STUDY II.  According to findings published in 2010, of 102 patients with RA, 55% of those who attained low disease activity on infliximab were able to discontinue the drug for more than 1 year without radiologically detectable joint destruction.

Results from the HONOR study, reported in 2016, suggested the same long-term, medication-free 

. The study enrolled 197 patients with RA treated with adalimumab. One year after discontinuation, 79% of patients who began the period with deep remission had not experienced flaring of inflammation and showed no functional or structural damage. The study also found that readministration of the drug to patients with flare-ups was effective in controlling RA.

Despite such findings, more needs to be known about “optimal approaches for discontinuation,” the investigators wrote.

In IFX-SIRIUS STUDY II, disease activity will be measured by musculoskeletal ultrasound as well as by clinical disease activity in order to accurately assess inflammation at the joint level. Investigators will also measure serum levels of cytokines and chemokines to determine whether these biomarkers can predict nonclinical relapse after discontinuation of biosimilar infliximab.

“We expect that a certain proportion of patients with RA will have clinical relapse after discontinuation of CT-P13; thus, we will also evaluate the effectiveness and safety of CT-P13 retreatment in patients with RA who have clinical relapse,” they said.

The prospective, interventional, single-arm, multicenter study based in Japan will begin with enrollment of ≤ 80 patients and baseline screening, followed by evaluations at 3-month intervals and final evaluation at 48 weeks. For enrollment, patients must have been on biosimilar infliximab during the IFX-SIRIUS STUDY I and have experienced a nonclinical relapse during that study period.

Patients will discontinue CT-P13 at points throughout the study period, and if they have a relapse following discontinuation, CT-P13 will be readministered.

The primary end point is the proportion of patients who had clinical relapse during the 48-week period.

Japanese investigators say more needs to be known about what happens post treatment with biosimilar infliximab in patients with rheumatoid arthritis (RA).
 

Study to Evaluate Discontinuation of Biosimilar RA Treatment

The expiration of biologics patents has created opportunity for new biopharmaceutical industry to step in with biosimilars. Although this opportunity is recognized in India, the country needs to develop top-down quality to improve standards and procedures, according to a panel of international experts.

“With this changing landscape, industry must evaluate the relevance of quality management systems,” the group wrote about the direction India must go to become a world-class player in biosimilars and biologics in general.

 was the result of a meeting last year of representatives from United States Pharmacopeia, the Association of Biotechnology Led Enterprises, the FDA, and the World Health Organization. India has standout companies that are 

 on the world stage with their medicinal products, including biosimilars, but it is dogged by concerns that there is substantial room for improvement in its pharmaceutical industry overall.

The group recommended that a “culture of quality” be developed starting in the educational system with training programs on quality processes and a “focus on quality beyond compliance.”

“The curriculum in universities should include knowledge of quality management processes in the biopharmaceutical industry to inculcate [a] quality mindset very early into the students,” the report said.

Further, it recommended that heavier reliance be placed on automation and digitization to ensure accuracy, measurability, and appropriate record keeping.

The recommendations included an emphasis on pharmacovigilance partly because biosimilars undergo fewer clinical trials than originator products and follow-up data are crucial to understand these products.

“Biologics are complex molecules and manufacturing them requires changes at various stages of the manufacturing process,” the report said. “Manufacturers are required to perform rigorous risk assessments through analytical comparability studies for all product quality attributes to demonstrate that there is no impact on quality, safety, and efficacy of the biologics, before or after changes in manufacturing process.”

To accomplish these assessments, it’s necessary to have a comprehensive understanding of the biological product and its development from a “quality by design” perspective, the panel said.

Further, “to develop the necessary culture of quality, manufacturers must first establish robust and rugged control processes,” the report said.

Guidelines for biologic similarity in India were first published in 2012 and then revised in 2016.

The panel said typical red flags during quality inspections worldwide include:

Absence of written procedures or procedures not followed correctly

Failure to investigate discrepancies and failures

Lack of cleaning, sanitizing and maintenance

Absence of control procedures to monitor and validate performance

Lack of computer control of master records

Quality, the panel said, starts with ensuring that all involved understand their responsibility for developing and maintaining quality and protecting patient safety, “and this must be instilled from top management.” It said building a culture of quality could be done with:

Discussing how to enhance scientific knowledge

Forming partnerships with regulatory agencies and consultants

The group specifically recommended that India enhance its focus on automation and digitization, enforcement of regulatory requirements, postmarketing surveillance, and regulator training.  Developing a culture of quality could be done by stimulating effective communication and decision making, assigning clear responsibilities, establishing safety protocols, and building trust and respect among staff.

“Defining and ensuring trust and respect among staff is essential to create and maintain a culture of quality. Trusted employees will contribute more, bring more productivity, and will be honest in their actions,” the report said.

 to upgrade its regulatory processes to meet world standards and enable its drugs to be more accepted in world markets.

Uppal A, Koduri CK, Yadlapalli S, Chirmule N, Chakrabarti R, Atouf F. Recommendations for enhancing quality and capability of Indian biopharmaceutical industry: summary of a workshop. 

. Published online July 21, 2020. doi:10.1016/j.xphs.2020.07.014

United States Pharmacopeia (USP), the FDA, and others deliver constructive critique on how India can bolster quality in its biopharmaceutical industry.

USP Panel Recommends Quality Upgrade for India's Biopharmaceutical Industry

A high overall response rate (ORR) of 88% marked results for the first real-world clinical trial of biosimilar rituximab in combination with chemotherapy in patients with CD20-positive diffuse large B-cell lymphoma (DLBCL), confirming the expected efficacy and safety profile of the agent, according to lead author Manfred Welslau, MD.

The biosimilar chosen for the trial was a Sandoz product, marketed in the European Union under the names Riximyo and Rixathon. It is not currently approved or available in the United States. Welslau discussed the trial in an 

The biosimilar was evaluated in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). “We don’t see any difference between the rituximab biosimilar and the reference product,” Welslau said.

In Europe, rituximab and trastuzumab biosimilars are used about 80% of the time versus 20% for the originators, Welslau said.

“We decided to do this trial even though the biosimilar was already approved in Germany,” he said. “The rituximab biosimilar was already approved because of the significant improvement in follicular lymphoma, and there was extrapolation to all the other indications of reference rituximab, even in rheumatic diseases.”

However, clinicians wanted more information about the equivalency of the Sandoz biosimilar to the reference product in DLBCL, Welslau said.

“We didn't have any clinical data on biosimilars in combination with CHOP in patients with DLBCL. We decided to conduct a trial in over 30 centers in Germany using the rituximab biosimilar instead of reference rituximab. We examined the efficacy and toxicity of the therapy.”

Interim results were presented at the 2020 ASCO Virtual Scientific Program. The ORR was comprised of a 57% complete response and a 31% partial response. Efficacy data were incomplete and the progression-free survival (PFS) data have not yet been reported. Overall, 38% of patients completed the first 12-month observation period, while 41% were continuing treatment and 21% discontinued due to progressive disease.

Adverse events leading to discontinuation of the therapy were observed in 8% of patients. Those included anemia, neutropenia, and fatigue and were the same as for the originator product.

Investigators are still awaiting 24-month PFS data. “In DLBCL, the 24-month PFS is strongly correlated with OS. We should see a good signal for the efficacy of the rituximab [biosimilar] in this patient population.

However, “the take-home message is that you can use the rituximab biosimilar safely and effectively in the treatment of patients with DLBCL,” Welslau said.

In the United States there are 2 rituximab biosimilars on the market: Truxima (Celltrion/Teva) and Ruxience (Pfizer). More competition is anticipated. Amgen and AbbVie (formerly Allergan) in December 2019 

a Biologics License Application for ABP 798.

Welslau M, Walter N, Otremba BJ, et al. REFLECT real-world evidence prospective study update: efficacy and safety results of Sandoz biosimilar rituximab for the treatment of diffuse large B-cell lymphoma. 

 2020;38(suppl 15):8060. doi: 10.1200/JCO.2020.38.15_suppl.8060

A rituximab biosimilar in diffuse large B-cell lymphoma (DLBCL) passes the real-world test with flying colors, according to Manfred Weslau, MD.
 

Sandoz Rituximab Measures Up in DLBCL

Incheon, Republic of Korea—based Samsung Bioepis has launched its trastuzumab biosimilar Ontruzant in Brazil for the treatment of patients with early and metastatic HER2-positive breast cancer and advanced gastric cancer.

The drug references Herceptin and was previously approved by the Agência Nacional de Vigilância Sanitária in May 2019. Besides Brazil, Ontruzant is currently marketed in Australia, Europe, the United States, Ukraine and Republic of Korea. It received authorizations in Europe and the United States in 2017 and 2019, respectively.

“The launch of our first oncology treatment Ontruzant in Brazil is a step closer to realizing our mission which is to deliver high quality, proven biologic medicines to more people, said Josh Sang Hyun Lee, vice president and commercial strategy team lead, Samsung Bioepis.

Breast cancer is the most common cancer and main cause of death among women in Brazil. There are an estimated 67,000 deaths from this disease each year in Brazil and the number is growing by 2.54% each year, Samsung Bioepis said in a statement.

 by McKinsey & Company, the potential scope of Brazil’s biosimilar market ranked second in the world among emerging countries. McKinsey projected a market size of $1.9 billion by 2025 with an annual growth rate of 25% to 30%. That was larger than the projection for India ($1.4 billion; 15%-20% growth), but well short of China’s ($8.1 billion; 20%-25%).

In Brazil, biologics account for less than 5% of volume of drug sales but roughly 40% of health ministry spending on drugs, according to McKinsey. The drug approval pathway in Brazil is based on World Health Organization and European Medicines Agency guidelines.

Ontruzant is being supplied to the country’s public health system, Sistema Único de Saúde, through a partnership between Samsung Bioepis and local partners, Bionovis and Bio-Manguinhos.

Samsung Bioepis was established in 2012 and is developing biosimilars in immunology, oncology, ophthalmology, and hematology. It is a joint venture between Samsung BioLogics and Biogen.

In June, the company initiated a phase 3 

 for its aflibercept biosimilar SB15, referencing Eylea. The randomized multicenter study will compare the efficacy, safety, pharmacokinetics, and immunogenicity between the biosimilar and the reference product in 446 patients with neovascular age-related macular degeneration.

The company also has a ranibizumab (SB11) ophthalmology candidate in clinical development.

Also in June, the company’s bevacizumab candidate (Aybintio), referencing Avastin, was 

 for marketing authorization by the European Medicines Agency. The drug was recommended for the same indications as the reference product, including metastatic carcinoma of the colon or rectum, metastatic breast cancer, non—small cell lung cancer, advanced or metastatic renal cell cancer, epithelial ovarian, fallopian tube and primary peritoneal cancer, and cervical cancer.

In early August, Samsung Bioepis announced it had received a prestigious Red Dot Design 

 for its innovative packaging design featuring natural shapes and colors designed to inspire confidence and peace in patients and “move away from the conventional, rigid design of medicine packaging” focused only on delivery of safety information.

Samsung Bioepis makes a move into the promising Brazilian market for biosimilars, which data suggest is one of the fastest-growing biosimilars markets among emerging nations.

Samsung Bioepis Enters Breast and Gastric Market in Brazil

A study of caps placed on out-of-pocket (OOP) costs for specialty drugs demonstrated that the caps did not lead to an increase in health care spending except for patients at the highest tier (95th percentile) of spending, investigators wrote.

They concluded that this showed that the caps were doing what they were supposed to do: protect the patients most vulnerable to high OOP costs without leading to across-the-board health care spending increases.

The study included records for 27,161 patients, from 2011 to 2016, covered by 3 national payers. Among patients in the 95th percentile of spending on specialty drugs, OOP costs were $351 lower per user per month, which represented a decrease of 32% in spending, investigators said.

Investigators noted that not enough is known about the effects of caps on patient costs, and they sought to remedy this deficit via their study. They noted that specialty drugs such as antiviral agents for hepatitis C and biologic agents for multiple sclerosis or rheumatoid arthritis are highly effective but spending for these agents is 

“Over the past decade, health-plan spending for such treatments increased from an estimated 26% of total drug spending to 49%, while the treatments remained below 2.5% of total prescriptions dispensed,” they wrote.

Meanwhile, the use of high cost-sharing drug tiers among employer sponsored health plans has risen from 11% to 51%, with a simultaneous increase in the disparity in OOP spending between specialty drug users and nonspecialtiy drug users, “becoming 3 times as large as that in an earlier 10-year period,” the authors wrote.

In just the past 2 years, at least 21 states and the federal government have introduced legislation to control OOP patient costs for prescription drugs, and 11 states have introduced laws targeting specialty drug spending. Of the latter group, Delaware, Louisiana, and Maryland passed legislation and imposed caps on OOP for commercial health plans at $150 per 30-day supply of specialty medication, the authors wrote.

Investigators said their concern was that they would find that caps would lead to increased health plan spending followed by increases in insurance premiums and reduced insurance affordability for all enrollees. This did not happen.

However, investigators evaluated outcomes 1 to 3 years after the cap policies were implemented. They noted it’s possible there will be a delayed impact on payer policy: “Subsequent effects may include health plans restricting the use of specialty drugs, through more stringent prior authorizations or higher deductibles, or manufacturers increasing drug prices because of reduced out-of-pocket costs.”

“The caps were not associated with changes in out-of-pocket spending for specialty-drug users at the lower spending quantiles, in mean out-of-pocket spending, or in overall specialty-drug utilization (which increased only in Delaware),” they wrote.

They observed that there was a larger change in spending for individuals with hepatitis C than for patients with other conditions, suggesting that caps “may be more effective at protecting against very high out-of-pocket prices incurred over a shorter duration.”

Overall, they said their study findings indicate that caps may be “well aligned” with the fundamental principals of using health insurance to mitigate the impact of high individual costs for health care.

“Insurance functions best when it provides coverage for treatments that are high cost, that are for rare conditions, and that patients value (eg, treatments for which changes in OOP prices do not substantially alter utilization behavior),” they wrote.

With specialty drug costs becoming a larger and larger influence on health budgets, it’s inevitable that policies, such as OOP caps, will evolve to manage this spending, the authors concluded. “It would be useful to evaluate these caps in the longer term, as well as spending caps of other types and magnitudes, to inform the balance of individual and population financial burdens of these important medicines.”

Yeung K, Barthold D, Dusetzina SB, Basu A. Patient and plan spending after state specialty-drug out-of-pocket spending caps. 

. 2020;383:558-566. doi:10.1056/NEJMsa1910366

Investigators set out to learn whether the imposition of out-of-pocket spending caps on specialty drugs would unleash a wave of drug spending and prompt payer policy change.