Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

The Academy of Managed Care Pharmacy (AMCP) has kicked off an effort to promote biosimilar use by developing strategies and consensus at a 2-day summit involving various stakeholders.

“AMCP is dedicated to continue partnering with managed care pharmacy stakeholders to implement these strategies and advocate for biologic to be accepted as safe and effective therapeutic options, as well as increase access to them,” said AMCP CEO 

 to improve education about biosimilars, agree on best practices regarding use, promote the collection of real-world evidence and postmarketing data on biosimilar adverse events, review policies for coverage of biosimilars under the pharmacy benefit, oppose anticompetitive practices, and bolster public support for FDA approvals.

“Some of the complexities from the health plan side, including contracting arrangements, may reduce or remove the anticipated cost savings of a biosimilar vs the reference biologic,” the group wrote in a summary statement.

They identified a need to overcome clinical and administrative barriers to biosimilar use that add to the difficulties of matching patients with biosimilars that would address their health needs. “With complexities around setting up the [electronic medical records] and order sets in each provider system, particularly given that each patient might be associated with different payers and formularies, it can be difficult for providers to determine the right biosimilar that will provide the right treatment at the right cost for a given patient, especially when the biosimilar is one drug in a multi-drug regimen.”

The summit participants also concluded that in some cases originator brand biologics may come with robust patient support programs, and taken as a whole these may supply compelling reasons to prefer reference products over biosimilars. 

In addition, there’s a need to overcome pubic “mistrust of science in general and the drug approval process in particular,” and the group aims to work on this, too.

Getting all this done will be no easy task, they said. “A variety of factors cause the biosimilar landscape to be highly complex and diversified. These include different approval pathways due to the complexity of molecules, differing benefit types and sites of care, complex electronic medical record (EMR) systems and order sets, differences in administration routes and approved indications, confusion around terminology, physician clinical specialties, and the differing needs of patients depending on the disease state as well as whether they are treatment-naïve. All of these complexities present an overall challenge from which many other challenges flow.”

In mapping out its future path to accomplish these objectives, the group said it would publish a proceedings document with its findings and recommendations, support that dissemination with a webinar, construct other educational programs, find ways to incentivize biosimilar uptake, and recruit more participants and stakeholders to help with the overall process. 

Articles

A partnership forum sponsored by the Academy of Managed Care Pharmacy (AMCP) yielded numerous ideas for improving access to biosimilars.

AMCP Sets a Course for Biosimilar Promotion

A Guangzhou, China, company that has submitted a bevacizumab biosimilar candidate for regulatory approval in China and Europe is moving ahead with a 

Bio-Thera Solutions has developed BAT1706 and recently completed a phase 3 comparative clinical study demonstrating equivalence to the reference product (Avastin) for efficacy, safety, pharmacokinetics, and immunogenicity in patients with advanced nonsquamous non–small cell lung cancer who also received chemotherapy.

The company now has contracted for Biomm SA to submit the regulatory paperwork for BAT1706 in Brazil and handle the product distribution in that market. “This partnership will leverage Biomm’s strong local presence, sales, and marketing capabilities in Brazil,” Bio-Thera said in a statement that also explained that it would handle the product manufacturing side of the partnership, utilizing its biopharmaceutical plant in Guangzhou.

“This partnership is the first to expand Bio-Thera’s presence into Brazil, an important pharmaceutical market for biosimilars and innovative drugs,” Shengfeng Li, CEO of Bio-Thera, said in the statement.

BAT1706 is intended for the treatment of patients with metastatic colorectal cancer; metastatic or locally recurrent breast cancer; locally advanced, metastatic, or recurrent non–small cell lung cancer; metastatic renal cell carcinoma; persistent, recurrent, or metastatic cervical cancer; and epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Heraldo Marchezini, CEO of Biomm, said his company was eager to expand its activities in the oncology biologics space. "Biomm is committed to expanding its portfolio in biotechnology with a long-term vision, especially in ​​oncology where is critical to expand the access to modern treatments.”

In September 2020, Bio-Thera announced distribution partners for the marketing of BAT1706 in 

 the first adalimumab biosimilar (Qletli) in China.

Building on regulatory submissions elsewhere, the company is looking to gain approval for bevacizumab candidate BAT1706 in Brazil.

Bio-Thera Seeks to Enter Brazilian Market for Bevacizumab

In developing a perspective on biosimilar awareness in Europe, Samsung Bioepis started with a hypothesis that it ended up disproving—namely, that biosimilars are well known and understood by both patients and health care providers (HCPs).

“Overall, our findings show that the biosimilar conversation in both the media and among key opinion leaders is immature,” the Incheon, Repubic of Korea, biosimilar development company concluded in a 

European physicians don’t appear to be doing enough to inform patients about biosimilars, even though patients are better informed now than in the past and often come to clinic appointments prepared with their own research on treatment options, the report said. But patients themselves often do not understand what biosimilars are—that they offer comparable safety and efficacy to reference brands and may represent a potential for health care savings.

“Biosimilar education for HCPs and patients remains one of the keys to unlocking the true potential of biosimilars in Europe,” the authors wrote. “Put simply, HCPs need to fully understand the merits and value of each individual biosimilar, while patients need to feel confident in the treatment that they are prescribed.”

What’s preventing broader awareness of biosimilars and higher utilization are knowledge gaps and approaches to disseminating information that are inadequate, the authors said. For example, in Italy, 80% of HCPs surveyed said they don’t have basic information about what biosimilars contain and how they function.

 used crowdsourcing to learn about biosimilar awareness in France, Germany, Italy, Spain, and the United Kingdom. This involved a study of biosimilar mentions across media outlets and in conversations engaged in by HCPs, academics, journalists, patient advocates, and drug policy experts. This information was supplemented by a series of 3 panel discussions with HCPs.

“We found that a lack of understanding prevails across all countries, with HCPs aware that the prescription rules are shifting at pace but unsure what comes next,” the authors said.

The white paper said the strongest voices for biosimilars were found amongst patient advocacy groups, “especially when there are new treatments in their therapy area.” However, the report said even this advocacy often falls short of hoped-for outcomes.

Efforts have been made to facilitate a more robust dialogue between providers and patients about the merits of biosimilars, but in many cases there is no conversation at all, according to the white paper. “Despite 77% of patients being switched from a reference biologic drug to a biosimilar, only 51% had received any explanation for the switch,” according to a survey of patients in Italy cited by the authors.

The report also said that without physician support in the form of a biosimilar discussion, the nocebo effect, where a patient’s negative expectations affect outcomes, is liable to frustrate goals of care. Further, among HCPs, “many believe that the more you pay for a drug, the better it will perform.” 

Much can be achieved by creating educational materials and programs that HCPs will find digestible, given their busy schedules, the report said. “Many physicians are too busy to study in-depth clinical trials data and would prefer to see easily digestible educational materials on biosimilars’ safety, equivalence, and cost savings.”

In the EU-5 group of countries, biosimilar awareness is poor, hindering uptake of these potentially cost-saving medicines, a white paper states. 

Samsung Bioepis Examines European Awareness of Biosimilars

The Sandoz adalimumab biosimilar Hyrimoz has been 

by Health Canada for the treatment of 9 rheumatologic and gastrointestinal conditions—in effect, all the indications as for the reference brand, Humira.

Adalimumab is a fully human tumor necrosis factor (TNF) blocker that helps to reduce inflammation. Health Canada granted marketing authorization for Hyrimoz in 3 subcutaneous injection dosage forms: 40 mg/0.8 mL and 20 mg/0.4mL in prefilled syringe, 40 mg/0.8 mL in autoinjector.

The indications include rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, hidradenitis suppurativa, psoriasis and adult uveitis.

Sandoz Canada executive Karine Matteau said in a statement that the company intended to launch Hyrimoz by February 15, 2021, and said market potential is promising as 42,000 Canadian patients already receive treatment with adalimumab.

“We are currently working on the reimbursement of Hyrimoz to enable rapid access for patients.” said Matteau, vice president, Bio-Generic Hospital/Physician channel and Head Biosimilars at Sandoz Canada. “Sandoz is dedicated to growing our biosimilars portfolio in Canada and Hyrimoz is an important driver for this in the immunology area, as it complements the recent biosimilar launches we had this year in immunology and oncology.” In Canada, the company markets biosimilars for oncology, immunology, and endocrinology. These compete in a national market that has seen 32 biosimilar approvals to date, Sandoz Canada said.

Sandoz Canada said it would support the rollout with patient support that includes reimbursement navigation, financial assistance, administrative support, and a biosimilar education program for patients.

The regulatory approval for Hyrimoz marks the 

for the company in Canada over the past 11 months. In August 2020, Sandoz Canada launched the pegfilgrastim and rituximab biosimilars Ziextenzo and Riximyo, respectively. Both agents were approved by Health Canada in April 2020.

The Canada Health approval for Hyrimoz will be followed by a launch in February 2021, Sandoz Canada said.

Sandoz Canada Gains Marketing Approval for Adalimumab Biosimilar

Amgen's rituximab biosimilar Riabni, which references Rituxan and is indicated for the treatment of adult patients with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia, granulomatosis with polyangiitis, and microscopic polyangiitis. Amgen said the product would be commercialized in the United States starting in January 2021. 

The approval milestone follows recent US biosimilar launches for Amgen including a trastuzumab (Kanjinti, 2019) and bevacizumab (Mvasi, 2019). The company has 10 biosimilars in total, 5 approved in the United States and 3 available in the European Union.

Riabni is a CD20-directed cytolytic antibody that has demonstrated biosimilarity to the reference product via comparative analytical, nonclinical, and clinical data. The totality of evidence included a pharmacokinetic similarity study and comparative clinical study, Amgen said.

Efficacy, pharmacokinetics (PK), pharmacodynamics (PD), safety, tolerability and immunogenicity were evaluated in patients with grade 1, 2, or 3a follicular B-cell NHL and low tumor burden. Investigators enrolled 256 patients and randomized them 1:1 to receive 375 mg/m

 intravenously of either the biosimilar or reference product, once weekly for 4 weeks, followed by dosing at weeks 12 and 20.

Amgen said the primary end point was overall response rate by week 28, which was within the prespecified margin for equivalence to Rituxan. PK, PD, safety, and immunogenicity also were equivalent, and no meaningful differences in safety or effectiveness were detected. 

The pharmaceutical company said Riabni will be marketed at a discount to the reference product of 23.7% below wholesale acquisition cost (WAC), or a WAC of $716.80 per 100 mg and $3584 per 500 mg single-dose vial.  These costs are 15.2% less than the WAC for the biosimilar rituximab Truxima, Amgen said. 

The company added that Riabni's average sales price will be 16.7% below the current average for Rituxan. 

The approval of the Amgen product marks the third biosimilar approval in the United States since the beginning of 2020. 

FDA Approves Rituximab Biosimilar "Riabni" From Amgen

 a phase 3 trial for a proposed denosumab biosimilar (SB16) referencing Prolia. The randomized, double-blind, multicenter study will evaluate SB16 for equivalent efficacy, safety, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity in a population of 432 women with postmenopausal osteoporosis.

Samsung Bioepis also began a phase 1 trial in October 2020 evaluating the same parameters for SB16 in healthy volunteers. In addition to SB16, the company has 2 other biosimilar candidates in development: eculizumab (SB12) and aflibercept (SB15).

In November 2020, Samsung Bioepis and Biogen 

 the FDA had accepted their application for a ranibizumab biosimilar candidate (SB11) referencing Lucentis. Ranibizumab is a vascular endothelial growth factor agent intended for treatment of retinal vascular disorders.

 1-year findings from a phase 3 study of SB11 in patients with neovascular age-related macular degeneration. The data presented at the American Academy of Ophthalmology 2020 meeting, held virtually this year, confirmed that SB11 has equivalent efficacy, safety, immunogenicity, and PK to the reference product.

The investigators said 634 patients of 705 enrolled completed the study up to week 52. Primary end points, defined as changes from baseline in best corrected visual acuity at week 8 and central subfield thickness at week 4, were met. They said efficacy, safety, PK, and immunogenicity were comparable to the reference product.

Samsung Bioepis hopes to gain regulatory approval for a denosumab biosimilar referencing Prolia. The trial will focus on women with postmenopausal osteoporosis.  

Samsung Bioepis Initiates Phase 3 Trial for Denosumab Biosimilar

Investigators studying trastuzumab biosimilar savings and use rates across different disease settings in human epidermal growth factor receptor 2 (HER2)-positive breast cancer observed dramatically increased usage of biosimilars and said payer policy appears to have contributed to higher biosimilar utilization.

They looked at treatment plans submitted for patients to determine usage rates for originator vs biosimilar trastuzumab and trastuzumab in combination with hyaluronidase-oysk. The average costs of originator and biosimilar trastuzumab per patient cycle were $4502 and $3618, respectively, with an average savings per biosimilar dose (440 mg, trastuzumab; 600 mg trastuzumab hyaluronidase) of $884. Total savings for 4502 patients with stage I to III disease was $24.4 million, according to the 

 presentation at the 2020 San Antonio Breast Cancer Symposium (SABCS).

Of 6657 treatment plans submitted for 4505 patients with stage 0 to III disease, the biosimilar usage rate was 34% (n = 2271 treatment plans). Investigators said that for 3312 plans submitted for 1933 patients with stage IV/recurrent disease, the biosimilar usage rate was 27% (n = 904 treatment plans).

The treatment plan submissions were tracked from June 2019 to October 2020 and showed a dramatic increase in biosimilar adoption. For patients with stage I to III disease, trastuzumab biosimilar use was 1.4% in the third quarter of 2019 vs 65.9 % in the fourth quarter of 2020. For patients with stage IV/recurrent disease, usage climbed from 1.6% to 49.3%, respectively.

Some patients had multiple treatment plans based on receipt of adjuvant or neoadjuvant therapy, treatment for local or recurrent disease, or metastatic/recurrent therapy. Patients with stage I to III disease were assumed to receive 1 year (18 doses) of trastuzumab therapy. Those with stage IV/recurrent disease were assumed to receive 11 months (16 cycles) of treatment.

The investigators said there was evidence that biosimilar use increased based on payer policies that favored biosimilars. Biosimilar use was 41.5% where payer policies were favorable vs 30.9% when that was not the case.

”As biosimilars were being introduced at different times during this time period and payer policy would likely lag behind these introductions, it is likely that the observed difference in biosimilar use by payer policy is underestimated,” the authors of the study wrote.

They concluded that the potential savings from biosimilar trastuzumab in breast cancer are “significant. Future estimates should use more rigorous models with stratification by use with hormonal therapy, chemotherapy, combinations with pertuzumab, or single agent, and the corresponding durations of therapy,” the authors recommended.

Flood WA, Avery T, Kozlovsky V, Margolis N, Reddy SK. Real world data on the adoption of trastuzumab biosimilars in the treatment of HER2-positive breast cancer. Poster presented at: SABCS; December 8-11, 2020. PS9-63. https://sabcs.onlineeventpro.freeman.com/single-file-viewer/25582299

In little over 1 year of use in patients with breast cancer, trastuzumab biosimilars have seen rapid growth in uptake. 

Investigators Demonstrate Dramatic Rise in Trastuzumab Biosimilar Use

Biocon Biologics, of Bangalore, India, and Mylan, of Canonsburg, Pennsylvania, have received a positive recommendation from the European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) for the marketing approval of their biosimilar insulin aspart candidate (Kixelle), a rapid-acting insulin for the treatment of type 1 and type 2 diabetes.

CHMP recommendations are a significant factor in final authorization for medicinal products from the European Commission (EC). Biocon and Mylan said they anticipate a final EC decision early in 2021.

Kixelle was recommended for marketing approval in injectable form (100 units/mL). Insulin aspart is fast-acting because it is absorbed more rapidly by the body and can act faster than human insulin. Like human insulin, aspart improves uptake of glucose into skeletal muscle and fat tissue and inhibits glucose output from the liver, according to the CHMP 

The biosimilar candidate references the originator brand insulin aspart NovoRapid, which was approved for EU distribution in September 1999. CHMP said data show that Kixelle has equivalent safety and efficacy. The product is recommended for adults, adolescents, and children older than 1 year.

“We are extremely pleased to receive a positive opinion…for our biosimilar Insulin aspart, co-developed with Mylan. This is an endorsement of the quality of our product and the data generated during its development,” 

Although there are no insulin biosimilars approved on the US market, there are multiple insulin biosimilars available in Europe. These include insulin glargine, insulin lispro, and insulin aspart versions. For example, an insulin glargine marketed by Eli Lilly received marketing authorization in 2014.

In June 2020, Biocon and Mylan received FDA approval to market the insulin glargine product Semglee (referencing Lantus) in the United States, and this was launched in late August 2020; however, it was not approved under the Biologics Price Competition and Innovation Act and is not technically a biosimilar. It was approved under the 505(b)(2) New Drug Application pathway for generic medicines. Biocon and Mylan said they intend to improve Semglee's marketability by seeking biosimilar status for the product. 

 for biologics under the Biologics Price Competition and Innovation Act was designed to help break the 

 held by a handful of innovator insulin products (Humalog, Eli Lilly; NovoLog, Novo Nordisk; Lantus, Sanofi) in the United States and allow biosimilar insulins to emerge and lower insulin prices. Heavy pressure by health care advocates, meanwhile, has brought about a lowering of co-pays and out-of-pocket costs for insulin products, improving access to these vital medicines. 

by Amerisource Bergen, there are several types of insulin biosimilars in the development pipeline for the US market. Participating companies include Biocon/Mylan, Diasome, and Gan & Lee/Sandoz.

The positive opinion from the Committee for Medicinal Products for Human Use (CHMP) is expected to be followed by a European Commission final decision early in 2021. 

Biocon/Mylan Receive CHMP Nod for Insulin Aspart Biosimilar in European Union

Australia’s Generic Biosimilars Medicines Association (GBMA) has 

named health policy expert Jane Halton, AO, PSM

, to chair the group in its efforts to expand access and affordable care. The GBMA is a trade association of generic and biosimilar medicine suppliers in Australia. Halton replaces Sylvain Vigneault, who has chaired the GBMA for 2 years.

Halton previously served as chair of the Coalition for Epidemic Preparedness Innovations and co-chair of COVAX, the vaccines component of the ACT Accelerator, a global collaboration to speed up the development and production of coronavirus disease 2019 (COVID-19) tests, treatments, and vaccines. She is also a former secretary of the Australian departments of Health and Finance.

with the Institute for Health Metrics and Evaluation, a global health research center at the University of Washington, Halton is described as having extensive experience with finance, insurance, risk management, information technology, human resources, health and aging, sport, public policy, and international affairs. She is also an adjunct professor at the University of Sydney and the university of Canberra. She has previously served on the executive board of the World Health Organization.

“To return to my domestic health policy roots and lead the GBMA, at such a significantly important time for Australian patients and our vital health care community, is a challenge I am delighted to embrace,” Halton said. “As we look to the arrival of a COVID-19 vaccine for our citizens, we also need to be vigilant that all Australians continue to receive the medicines they need, when they need them.”

Health care policy expert Jane Halton, AO, PSM, has been picked for her extensive experience in governmental health affairs.

Australian Biosimilar Trade Group Names New Chair

Celltrion’s high-concentration, citrate-free adalimumab biosimilar candidate (CT-P17, Yuflyma) has been 

recommended for marketing authorization by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency. The European Commission, which authorizes medicinal products for the European Union, will make the final decision, but is strongly influenced by CHMP.

CT-P17 is intended for the treatment of 12 chronic inflammatory diseases, including rheumatoid arthritis (RA), psoriatic arthritis, and Crohn disease. CHMP recommended approval for all 12. Celltrion said the positive opinion is based on equivalency studies demonstrating efficacy, pharmacokinetics (PK), and overall safety compared with the reference product, Humira.

CT-P17 would be the first high-concentration (100 mg/mL), citrate-free adalimumab biosimilar. “Having a high-concentration and citrate-free formulation would provide patients less pain during administration leading to improved quality of life,” said Edward Keystone, MD, FRCPC, senior consultant rheumatologist at Mount Sinai Hospital in Toronto, Canada, in a statement.

 versions of adalimumab in the European Union. There are 6 FDA-approved adalimumab biosimilars in the United States—but none of these is expected to reach market until 2023. A European Commission decision on the Celltrion product is expected in the first quarter of 2021.

The other proposed indications for CT-P17 are juvenile idiopathic arthritis, axial spondyloarthritis, psoriasis, pediatric plaque psoriasis, hidradenitis suppurativa, pediatric Crohn disease, ulcerative colitis, uveitis, and pediatric uveitis.

 of a phase 3 study in patients with RA was presented at the American College of Rheumatology Convergence 2020. In the randomized study, CT-P17 met the primary objective of efficacy and safety comparable to the standard for the reference product.

Efficacy, PK, and safety equivalence to the reference product also were demonstrated in a separate, randomized, double-blind, single-dose phase 1 study in healthy individuals up to 10 weeks. “The CHMP positive opinion is very encouraging as CT-P17 has demonstrated promising study results in efficacy, PK and safety profile compared to reference adalimumab,” Keystone said.

The recommendation from Europe's Committee for Medicinal Products for Human Use (CHMP) bodes well for a final marketing authorization for the adalimumab biosimilar candidate. 