Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

Recent clinical and real world evidence for Samsung Bioepis biosimilars for bevacizumab and trastuzumab support use of these products in place of the reference versions, David Planchard, MD, and Mark D. Pegram, MD, said at the European Society for Medical Oncology Congress Virtual 2020, in a review of study findings.

“People may know that biosimilars save money overall, but want to see that the data prove clinical similarity in a very controlled setting as well as in the real world,” said David Planchard, MD, of Institut Gustave Roussy (IGR) in Villejuif, France. Planchard serves as associate professor of medicine with the Thoracic Tumor Board at IGR.

The Samsung Bioepis bevacizumab biosimilar Aybintio (SB8) was approved in August for marketing by the European Commission. Samsung Bioepis’ trastuzumab biosimilar Ontruzant was launched in the United States in April.

Planchard noted that SB8 and the bevacizumab reference product (Avastin, BEV) have an “identical primary amino acid sequence and have demonstrated highly similar structural, physiochemical and biological properties.” A phase 3 trial randomized 763 patients with non–small cell lung cancer roughly equally to SB8 and BEV.

 Of those, 258 completed induction treatment with SB8 and 277 with BEV. The mean age of patients was 60.2 vs 60 in the respective arms.

In the full analysis set (FAS), equivalence was demonstrated in terms of best overall response rate (ORR) risk ratio and risk difference. The ORR in the FAS was 47.6% for SB8 vs 42.8% for BEV. In the per protocol set (PPS), the best ORR was 50.1% for SB8 vs 44.8% for BEV.

Median progression-free survival (PFS) in the FAS was 8.5 months for SB8 vs 7.9 months for BEV, and in PPS the median PFS was 8.5 months vs 7.9 months, respectively. Median overall survival (OS) in the FAS was 14.9 months vs 15.8 months, respectively; and in PPS, 14.8 months vs 15.8 months. Mean duration of response was 6.38 months vs 6.79 months, respectively, in the FAS; and 6.33 months vs 6.81 months in PPS.

Tumor burden change at 24-weeks from start of induction therapy in FAS was 0.6% (95% CI, –4.18% to 2.99%).

Overall responses also helped to demonstrate comparative efficacy in the trial arms. At cycle 2, there were 96 (28.5%) partial responses (PRs) in the SB8 group vs 88 (26.8%) in the BEV group; and stable disease was achieved by 202 (59.9%) and 201 (61.3%), respectively.

By cycle 6, the numbers were still close, demonstrating comparability. There were 97 (57.1%) and 83 (49.4%) PRs, respectively; and 60 (35.3%) and 70 (41.7%) SDs, Planchard said. At cycle 6, there was 1 (0.6%) complete response in the BEV group.

In terms of treatment emergent adverse events of special interest, proteinuria was observed in 2 instances in the SB8 arm (0.5%) and 7 patients (1.8%) in the BEV group. Hypertension was noted in 29 (7.7%) and 16 (4.2%) of each group, respectively.

Pharmacokinetic profiles also were highly comparable, Planchard said.

Pegram, director of the Breast Cancer Oncology Program at Stanford Women’s Cancer Center, Stanford University Cancer Institute, California, discussed real world data for biosimilar trastuzumab (SB3, Ontruzant) plus reference pertuzumab in early stage breast cancer.

He noted that a 56% pathological complete response rate (pCR) was noted in 215 Danish patients with HER2-positive breast cancer who received neoadjuvant chemotherapy plus SB3 plus pertuzumab, which he said was exactly comparable to historical trial evidence for the reference drug (Herceptin).

“Indeed, 68% of patients treated in the neoadjuvant setting with node-positive disease converted from lymph node–positive disease to lymph node–negative disease after treatment, so that’s also very reassuring and demonstrates the activity of this trastuzumab biosimilar when combined with pertuzumab,” he said.

In a separate study involving real-world outcomes of 35 patients from Austria with HER2-positive breast cancer who received chemotherapy plus SB3 plus pertuzumab, the safety and efficacy profile of SB3 plus pertuzumab was consistent with that of the reference product in that combination. Significantly, 22 patients treated in the neoadjuvant setting achieved a pCR of 50%; none of the 35 patients had a decline in left ventricular ejection fraction (LVEF) of more than 10%; and 2 patients had an LVEF decline of ≤ 5% after treatment. “This is also very reassuring in terms of cardiac safety signals,” Pegram said.

Importantly, Pegram said, “this recent real-world evidence supports the extrapolation of trastuzumab-dttb [SB3] to include combination [therapy] with pertuzumab.”

1. Planchard D, Pegram MD. Navigating the optimized oncology treatment options in colorectal cancer, lung cancer and breast cancer through multidisciplinary discussions: clinical evidences of biosimilars. Presented at: ESMO Congress Virtual 2020. 5389.

2. Reck M, Luft A, Bondarenko I, et al. A phase III randomized double-blind multicenter study to compare the efficacy, safety, pharmacokinetics, and immunogenicity between SB8 (proposed bevacizumab biosimilar) and reference bevacizumab in patients with metastatic or recurrent nonsquamous non-small cell lung cancer. Lung Cancer. 2020.

Articles

Biosimilars from Samsung Bioepis have demonstrated equivalency in clinical trial and real world settings, according to 2 prominent cancer specialists. 

Planchard, Pegram Review Evidence for Samsung Bioepis Biosimilars

 Advisory Board member Hope S. Rugo, MD, FASCO, has been 

among the winners of this year’s OncLive

 awards. Rugo, an investigator and breast cancer practitioner with the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco (UCSF), was named the recipient of the Education award.

She is among 15-world renowned leaders in oncology who will be officially honored at the Giants of Cancer Care

A video of the November ceremony will be available on demand after the event by visiting 

The many award categories include Cancer Diagnostics, Lymphoma, Community Outreach, and Translational Science.

Rugo has been a noted clinical research leader and lecturer at worldwide conferences. At UCSF, she runs the Breast Forum, which brings together patients, families, and caregivers for helpful information and discussion about managing breast cancer.

She had important investigational roles in the EMBRACA and ABRAZO studies, which evaluated the efficacy of talazoparib (Talzenna), a poly(ADP-ribose) polymerase that prevents damaged cancer cells from repairing themselves, thereby impairing tumor growth. This important drug was approved by the FDA in 2018 for patients with HER2-negative locally advanced or metastatic breast cancer with germline 

Rugo was also involved in evaluation of atezolizumab (Tecentriq) in the IMpassion130 trial, which led to the FDA’s March 2019 approval of the immunotherapeutic agent in combination with nab-paclitaxel (Abraxane) for PD-L1–positive unresectable locally advanced or metastatic triple-negative breast cancer. Tecentriq prevents cancer cells from disabling the immune system and preventing attacks on cancer cells.

Rugo has also contributed to the approvals of scalp-cooling technology to reduce chemotherapy-induced hair loss and a steroid mouthwash to relieve oral inflammation resulting from targeted therapy.

At Helen Diller, Rugo is director of the Breast Oncology Clinical Trials Program and a clinical professor of medicine. She holds a postdoctoral award from the AP Giannini Foundation (1990) and has been honored by Friends of the Breast Care Center (2006) and Cancer Care National Organization (2010).

 for a video of Rugo talking about the need for education to improve biosimilar uptake.

 to be honored at the November event are listed below: 

, Université Libre de Bruxelles and Jules Bordet Institute

, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco

, Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University

, Chao Family Comprehensive Cancer Center, University of California, Irvine

, Dana-Farber Cancer Institute and Harvard Medical School

, Massachusetts General Hospital Cancer Center and Harvard Medical School

Winship Cancer Institute of Emory University

Supportive, Palliative, and/or Geriatric Care — 

, Albert Einstein College of Medicine and Jacobi Medical Center

, The University of Texas MD Anderson Cancer Center

Breast cancer specialist Hope S. Rugo, MD, FASCO, an advisory board member for The Center for Biosimilars®, has been at the forefront of groundbreaking oncology advancements. 

Rugo Wins Prestigious Giants of Cancer Care® Award

Lotus Pharmaceutical and Chong Kun Dang (CKD) Pharmaceutical have entered into a distribution 

 for biosimilar darbepoetin alpha (CKD-1110), a second-generation epoetin for the treatment of anemia associated with chronic renal failure (CRF).

The drug references Nesp/Aranesp sold by Japan-based Kyowa Kirin, and Lotus noted in its statement that sales of this originator have grown 15% annually over the past 3 years.

CKD received approval to market the biosimilar in October 2019 from the Japanese Ministry of Health, Labor and Welfare. The company touted CKD-1110 as the first darbepoetin alpha biosimilar.

The collaboration gives Lotus the marketing rights for distribution of the product in Taiwan and South East Asian markets, a franchise that Lotus valued at around $30 million yearly. The status of regulatory approvals for CKD-1110 in Taiwan and South East Asia was not indicated.

The market for darbepoetin alpha in Asia is considered robust because CRF is among the top causes of death. In the United States, 15% of US adults are 

 to have CRF (ratio, > 1:7), a percentage consistent with a global market rate cited by Lotus. More than 37% of US adults 65 years and older have CRF.

“This deal not only strengthens our nephrology franchise in in the region, but also enhances our regional presence by adding more complex products to our growing biosimilars portfolio,” Petar Vazharov, CEO of Lotus, said.

Lotus, a diverse biopharmaceutical supplier, has identified movement into biosimilars as a valuable growth engine for its pharmaceuticals distribution network in Asia. The company has a pre-existing 

 with Reykjavik, Iceland–based Alvotech, a company that specializes in development and manufacturing of biosimilars and in August announced a partnership to collaborate with Teva to bring biosimilars to the US market. Teva would fulfill a commercialization role in that partnership.

Alvotech is an independent sister company to Alvogen, which in 2014 acquired a 67% stake in Lotus in a deal valued at $200 million. Lotus then took over management of Alvogen’s Asian operations. At the time, Lotus had an FDA-approved manufacturing facility for cytotoxic oral formulations. The partnership gave Lotus and Alvogen manufacturing and product development resources in North America, Taiwan, South Korea, and Romania.

The deal with Alvogen also gave Lotus access to a 30-country sales and marketing 

. At the time, the 2 companies intended to collaborate on developing difficult-to-produce generic products for the US market.

The Lotus deal with CKD gives Lotus 5 biosimilar products in its pipeline of products targeted for distribution in Asian markets. The others include bevacizumab, adalimumab, trastuzumab, and teriparatide products.

Lotus and CKD Pharmaceutical intend to be among the first to bring a darbepoetin alpha biosimilar to Southeast Asia.

Lotus Inks Deal With CKD to Distribute Darbepoetin Alpha Biosimilar

Positive pharmacokinetic (PK) equivalency data were presented for PrestigePharma’s trastuzumab biosimilar candidate (HD201, Tuznue), at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

PrestigePharma is a Singapore-based biopharmaceutical company that has an application for HD201 under review with the European Medicines Agency. The company previously reported positive biosimilarity findings for HD201 at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology.

In the ESMO data, PrestigePharma reported PK equivalence between HD201 and 2 versions of the reference product sold in the United States (US-Herceptin) and Europe (EU Herceptin), based on findings from a randomized, phase 1 trial (TROIKA-I, NCT03776240). Investigators said 105 healthy male subjects randomized to 3 arms received the biosimilar candidate and reference versions at an intravenous dose of 6 mg/kg for 90 minutes.

The HD201 and Herceptin trastuzumab versions were compared based on primary end points including peak concentration and total drug exposure. PK equivalence for HD201 was considered met if the confidence intervals were within conventional equivalence margins of 80% and 125%. Secondary end points included other PK parameters, safety, tolerability, and immunogenicity. 

Investigators said HD201 demonstrated PK equivalence for all criteria. They said the incidence of adverse events was lower in the HD201 cohort (20%) compared with the EU Herceptin (34.3%) and US-Herceptin (31.4%) groups. The most common adverse events were infusion-related reactions and administration site reactions.

 from TROIKA-I and TROIKA, which involved patients with HER2-positive early stage breast cancer. These earlier results indicated that the biosimilar was safe and well tolerated with PK comparable to Herceptin. In TROIKA, patients received HD201 or EU-Herceptin with chemotherapy in the neoadjuvant setting followed by trastuzumab monotherapy in the adjuvant phase.

The total pathological complete response rate was 46.6% for patients in the HD201 arm versus 46.2% in the Herceptin arm. The overall response rate was 90.8% vs 89.4%, respectively. TROIKA had 574 patents evaluable for response for the ASCO report, and the study remains ongoing (NCT03013504).

HD201 is the lead biosimilar candidate under development at PrestigePharma. The company also has bevacizumab and adalimumab biosimilars in development.

Demarchi M, Coliat P, Chung Shii Hii J, et al. A double-blind, randomized, parallel group study to demonstrate the equivalent pharmacokinetic properties of a single intravenous dose HD201, a trastuzumab biosimilar candidate, versus EU trastuzumab and US trastuzumab. Poster presented at ESMO Virtual Congress 2020; September 17, 2020. Abstract 590P.

Singapore-based PrestigePharma presents fresh equivalency data supporting its case for regulatory approval of HD201.

PrestigePharma Reports Positive PK Data for Bevacizumab Candidate

A dysfunctional regulatory and market system is responsible for the high prices of drugs and the slim foothold that biosimilars have achieved so far in the marketplace, according to a position 

 from the American College of Physicians (ACP).

The group describes numerous structural impediments that hinder market entry for lower-cost drugs and allow pharmaceutical companies to leverage larger and larger revenues from their original brand products without a commensurate increase in health care consumer value.

ACP suggests multiple policy changes that would remove or loosen the blocks and wedges and allow competitors to step in with biosimilars and generic products that would lower health care costs without stifling innovation.

“New policies should be implemented to prevent market manipulation, help lower-cost alternatives make it to the market faster, and ensure a robust and competitive market for generic and biosimilar drugs,” ACP said.

The United States produces 57% more new drugs than the United Kingdom, Japan, Germany, and France combined, but many new drugs are simply repurposed old drugs with new indications, and meanwhile, there are thousands of rare diseases for which treatments exist for only a tiny fraction, ACP said.

Many Americans have benefited from the development of “orphan drugs” for niche health conditions (≤ 200,000 patients), but these are generally very costly, and ACP states that an orphan drug might be only a rare disease indication for a commonly used drug. Because of its orphan status, that same drug would be granted an additional 7 years of product exclusivity, preventing lower-cost competition from exerting downward pressure on pricing.

“This puts a strain on patients and families affected by rare diseases, who are often already exposed to high direct and indirect costs of medical care,” ACP noted.

ACP described the American marketplace as “unregulated” when it comes to pricing freedom enjoyed by pharmaceutical producers. “The list prices for the originator rheumatoid arthritis drugs Enbrel (etanercept, Amgen), Humira (adalimumab, AbbVie), and Xeljanz (tofacitinib, Pfizer) have increased by more than 100% since 2014,” the group said.

Biosimilars have been approved for etanercept and adalimumab but because of patent protections will effectively be kept off the market until 2029 and 2023, respectively. “Preventing lower-cost biosimilar or generic drugs from entering the market adds billions of dollars in costs to federal health care programs and affects the affordability and accessibility of drugs for patients who rely on them on a day-to-day basis,” ACP said.

Patent protections for biologics extend to 12 years in the United States, which the group said is excessive. Product exclusivity is often considered essential to reward companies for innovating and compensate them for the costs of developing a new drug; however, ACP argues that even after loss of exclusivity and biosimilar products enter the marketplace, a pharmaceutical company is able to continue making sizeable profits from a drug.

According to the Pacific Research Institute, the first biosimilar for filgrastim—and, in fact, the first-ever biosimilar in the United States—was launched in 2015, and since that time, filgrastim biosimilars have achieved only a 50.4% share of the marketplace for filgrastim, which supports the ACP’s contention that originator brands can continue making money after their patents have expired.

Manufacturers and industry insiders have contended that the 12-year window for product exclusivity is largely an illusion because many factors may 

 that time, such as a delayed approvals process. 

Insulin product approvals have recently come under regulation via the Biologics Price Competition and Innovation Act, which affords them biosimilar status if they are not originator drugs. It is hoped that this will lead to greater price competition, and ACP noted that the absence of competition for insulin products has allowed manufacturers to control the marketplace and steadily increase prices. “The annual cost per patient for treatment of type 1 diabetes doubled between 2012 and 2016, from $2864 to $5705,” the group said.

“Shadow pricing” is a type of marketplace abuse that ACP described as particularly damaging to health care consumers. With shadow pricing, a small number of dominant producers raise their prices almost in tandem. “Between 2009 and 2015, the prices of the insulin products Lantus (Sanofi-Aventis) and Levemir (Novo Nordisk) increased at or around the same time 13 times. Similarly, the prices of Humalog (Eli Lilly and Company) and NovoLog (Novo Nordisk) increased in conjunction 17 times over 10 years,” ACP said. 

The ACP called for legislative reform to the Orphan Drug Act to change incentives for development of these drugs. It supported reducing data and market exclusivity for biologic drugs from 12 years to 7 years and bringing a halt to “excessive patenting” on brand name and biologic drugs.

The group also called for elimination of direct-to-consumer (DTC) drug advertisements. “There is a lack of consensus in the economics literature about whether DTC advertising improves market performance or undercuts competition,” the ACP said.

Daniel H, Serchen J, Cooney TG. Policy recommendations to promote prescription drug competition: a position paper from the American College of Physicians. 

The American College of Physicians (ACP) said many reforms are needed to install appropriate checks and balances in the biologic drugs marketplace. 

ACP Calls for Biologics Marketplace Reforms

for Merck’s Brenzys etanercept biosimilar by Health Canada. Originally approved in 2016 for the treatment of moderate-to-severe rheumatoid arthritis in adults and ankylosing spondylitis, Brenzys now has several additional approved indications: plaque psoriasis (PsO), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA).

Brenzys references Enbrel, which is already indicated by Health Canada for all the above-named indications. The drug is administered by subcutaneous injection.

In its statement about the expanded uses, Merck noted that roughly 1 million residents of Canada live with psoriasis and, of those, at least 10% will go on to develop PsA.

Etanercept is a tumor necrosis factor (TNF) blocker that reduces the amount of TNF-alpha made by the body’s immune system. Too much TNF-alpha is a characteristic of PsO, PsA, and JIA. This overproduction leads to painful, swollen joints and the development of thick, red, scaly patches known as psoriatic skin lesions, which can appear on any part of the body. Etanercept helps to ease these conditions.

JIA is the most common type of arthritis in children under the age of 16 and in Canada, roughly 10,000 youths have this condition.

“Merck is committed to providing Canadians with more therapeutic choices for patients and their treaters,” Anna Van Acker, president of Merck Canada, said in the statement.

Under the category of PsO, Canada Health has approved Brenzys for the treatment of adults with chronic moderate-to-severe PsO who are candidates for systemic therapy or phototherapy and also pediatric patients 4 to 17 years of age with chronic severe PsO who are candidates for systemic therapy or phototherapy.

In patients aged 4 to 17 years with an inadequate response to disease-modifying antirheumatic drugs, Brenzys is approved for the treatment of moderate-to-severe polyarticular JIA.

Various Canadian provinces are moving aggressively toward implementation of biosimilars in an attempt to save money and improve access to health care. British Columbia is furthest ahead with these initiatives and recently reported total savings of $96.6 million, which it plowed back into health system investments that made other forms of care more available for patients.

In the most recent phase of this transition, British Columbia established 

to biosimilar rituximab for patients in its PharmaCare prescription coverage plan. Other Canadian provinces are following suit with similar switching programs, but the overall usage picture for biosimilars in Canada shows that the market for these drugs remains small. 

Biosimilars have 8% of the Canadian market relative to originator products. In the United States, biosimilars command just 2.3% of the biologics marketplace, according to a recent Pfizer presentation.

A broader range of indications in rheumatology combined with a Canadian push for biosimilar acceptance bodes well for Merck's Brenzys product. 

Merck's Etanercept Gains More Indications for Use in Canada

 resulting in a $70 million damage award for Amgen formed the crux of a recent panel discussion aimed at broadening understanding of when biosimilar developers may overstep and incur infringement liability.

Intellectual property law attorneys from Goodwin Procter of Boston discussed “safe harbor” laws that allow biosimilar developers some protection against patent infringement during the product development phase. The law tolerates, or allows, patent infringement if it is “reasonably related” to the development of evidence or information needed for a biologics license application to the FDA.

, the courts upheld the $70 million jury verdict that Hospira had infringed 2 patents in the development of a biosimilar for Amgen’s epoetin alfa (Epogen) product, a recombinant human erythropoietin for the treatment of anemia. The courts found that the safe harbor provision protected just 7 of 21 batches of drug substance created for the testing and development of Hospira’s biosimilar version of the Amgen product.

The law leaves open to interpretation just what the intention was in the use of patented material, and whether this use was strictly intended for the support of an application for biosimilar approval, the panelists said. The courts have acknowledged that transgressing patents may be necessary during the development stages even though, ultimately, the knowledge gathered and the uses to which the patented material was put were not directly related to the FDA approval application.

“A potential infringer does not lose protection for a particular activity just because many aspects of drug development have dual or multiple purposes,” said Josh Weinger, an associate in Goodwin’s Litigation Department. 

The safe harbor provision “extends beyond activities that are purely necessary to seek approval for a drug,” Weinger said. For example, safe harbor allows biosimilar developers “to experiment without perfect clarity with respect to what the FDA is going to require to demonstrate [biosimilarity], so even if the biosimilar developer is not entirely sure what they’re going to need to do to meet FDA requirements, they have a good deal of flexibility.”

“I think the main distinction ends up being whether the [batch] testing is sort of the foundational testing as part of the application, or if it’s more of a routine testing of that particular batch,” Weinger. He defined routine testing as that which occurs after the FDA application package is complete, which “is a situation where there will be more risk of the safe harbor not applying.”

, the jury distinguished between the batches specifically for regulatory approval and those that were not necessary for that purpose. A lot of power rests with the jury in making that distinction, and on appeal the jury verdict was affirmed by the district court (Delaware) and the Court of Appeals for the Federal Circuit. “It’s not clear that if the jury had come up the other way, that decision wouldn’t also have been affirmed, so I think the jury has a fair amount of discretion to come out either way,” Weinger said.

Panel moderator Elaine Blais, head of the Litigation Department in Goodwin’s Boston office, said that based on that outcome, parties to such a case should consider whether there are ways to steer the case to a jury trial or prevent that from happening, based on relative advantages. “There are always considerations whether you want a bench trial or a jury trial,” she said.

), which governs the unauthorized import of a product produced outside of the United States using a process patented inside the United States, which is considered infringement. This section also provides protection against infringement for processes that involve use of patents but result in a material alteration such that the patented product becomes a “trivial or nonessential component of” the final product.

“In the chemical and biotechnology context, the general rule is that a significant change in structure and properties would be a material change. Of course, that’s still somewhat ambiguous,” said panelist Kevin DeJong, an associate with the Goodwin litigation group. “The inquiry is definitely a context dependent, factual determination. “

The courts may also consider whether it would be impossible to make the product without the patented process in question. “For example, a product that can only be made by the patented process may not be considered to be materially changed,” he said.

This section of the law was created in 1988, and prior to that time patent owners had “no real remedy against infringers who would import a product into the United States when it was made outside the United States using the patent method,” DeJong said. The implication for biosimilar developers is that they should be diligent about understanding any patents that might be involved in, for example, cell culture processes and purification.

Courts have allowed biosimilar developers "safe harbor" against infringement suits, but there are limits, attorneys from Goodwin Proctor explain.

Goodwin Attorneys Discuss Hospira-Amgen Infringement Case

At the European Society for Medical Oncology (ESMO) Virtual Congress 2020 this week, detailed presentations will be 

biosimilar studies for agents from Mylan, Samsung Bioepis, and Shanghai Henlius Biotech.

Investigators plan to report phase 3 efficacy and safety data for Mylan’s proposed bevacizumab biosimilar MYL-14020 versus the reference product, Avastin, in the first-line treatment of patients with stage IV nonsquamous non–small cell lung cancer.

Investigators randomized 671 patients to the biosimilar candidate (n = 337) and Avastin (n = 334). In the preconference abstract, they reported that the confidence intervals for objective response rate (ORR) were within the predefined equivalence margins, demonstrating equivalence for MYL-14020.

 that the FDA had accepted its 351(k) filing application for MYL-14020. An application decision date was scheduled for December 27, 2020.

A poster on a randomized equivalence study for the Shanghai Henlius Biotech trastuzumab biosimilar (HLX02) also will be presented at ESMO. The multicenter study randomized women (N = 649) 1:1 to receive intravenous HLX02 or a European Union–marketed version of reference trastuzumab combined with docetaxel, with the primary end point being ORR at week 24.

In their preconference abstract, the investigators reported a 71.3% ORR for HLX02 vs 71.4% for the reference product. The group difference of 

7.0% to 6.9%) was “completely within the predefined equivalence margins of ±13.5%.”

In June, Henlius and Accord received a positive 

 for marketing approval for HLX02 from the European Medicines Agency.

Samsung Bioepis reported phase 3 exploratory 

 for its bevacizumab biosimilar (Aybintio) ahead of the scheduled ESMO poster presentation.

Positive results emerging on oncology biosimilars will be presented at the European Society for Medical Oncology Virtual Congress 2020 this week . 

Positive Equivalency Data for a Trio of Biosimilars Are Reported

positive phase 3 exploratory study results for its bevacizumab biosimilar, Aybintio, which received European Commission 

The findings are set for presentation at the European Society for Medical Oncology (ESMO) Virtual Congress 2020, which begins this week.

The Incheon, Republic of Korea–based company said the study results supported preexisting evidence in support of equivalence between Aybintio and reference bevacizumab in patients with metastatic or recurrent nonsquamous non–small cell lung cancer.

“The data observed in the phase 3 exploratory analyses reinforce equivalent clinical efficacy between Aybintio and reference bevacizumab,” said Seongwon Han, vice president and leader of the Medical & Lifecycle Safety Team at Samsung Bioepis.

The exploratory study enrolled 665 patients, of whom 337 received Aybintio and 328 were treated with reference bevacizumab with paclitaxel and carboplatin every 3 weeks for up to 6 cycles, followed by Aybintio or reference bevacizumab maintenance monotherapy. The risk difference was analyzed in the per-protocol set (PPS) within a predefined equivalence margin of ±12.5%.

The primary end point was overall response rate (ORR) after 24 weeks of induction therapy. In a previous analysis, the ORR in the PPS was 50.1% for Aybintio and 44.8% for reference bevacizumab, and the risk difference by week 24 was 5.3% (95% CI, 

2.2% to 12.9%). The risk difference is a comparative measure of the likely harms and benefits of therapies.

In the current study, the risk differences in best ORR by weeks 11 and 17 was 2.2% (95% CI, 

The mean reduction in tumor burden by week 24 was 

27.3% for reference bevacizumab, with a difference of 0.59% (

Samsung Bioepis said the results of the phase 3 exploratory analyses would be presented in an e-poster at ESMO during the virtual event’s Science Weekend on Thursday, September 17 at 9 AM Central European Summer Time.

Samsung Bioepis' bevacizumab biosimilar demonstrates equivalence in analyses to be presented at the European Society for Medical Oncology Virtual Congress 2020.

Samsung Bioepis Reports Positive Phase 3 Results for Aybintio

In a quest to ensure that product labeling disclosures about biosimilars are not unduly influencing the opinions of health care providers (HCPs) and consumers toward biosimilars, the FDA aims to conduct a study that will examine HCP and consumer responses to different types of label wording.

 about the draft outlines for the study, various pharmaceutical companies and groups have offered their suggestions for improving the value of these studies and upgrading standard biosimilar disclosures so that unwarranted perceptions do not form in the minds of HCPs and consumers.

“In the context of prescription drug promotion, there is initial evidence that—when noticed—disclosures may effectively convey important information; however, what role disclosures may play in educating or correcting misunderstanding warrants further investigation,” the FDA stated in describing the purpose of the study.

Promotional claims about biosimilars have been a focus for the FDA and Federal Trade Commission this year, as they endeavored to 

 to industry concerns that the public’s perception of biosimilars has been warped by multiple factors, including unintentionally and deliberately misleading promotions, from regulatory language to competitors’ claims about biosimilars.

The FDA plans to examine how label claims about nonprimary investigative goals, or secondary end points, in clinical studies will affect perceptions among HCPs and consumers. Participants enrolled in the study will view different versions of a website showing information about a fictitious product and answer questions based on their perceptions of that information.

The second part of the study will evaluate how disclosing that a drug product is a biosimilar affects HCP and consumer perceptions. Participants will also be asked to respond to various informational statements about biosimilars.

Study participants will also be asked for their reactions to multiple versions of language describing biosimilars and their relative safety and efficacy to reference products.

“This approach allows us to examine the effect of disclosing biosimilar status, examines the additive effect of including 1, 2, or 3 additional basic statements of information about biosimilars, and measures the effect of naming the reference product,” the FDA wrote.

In public comments about the study proposal, the Biosimilars Forum, representing biosimilars developers, said it was concerned about how language used to describe biosimilars may be “couched in cautionary or negative terms,” which hold the potential to be off-putting to HCPs and consumers.

It asked for a stronger emphasis in the study on garnering patient perceptions of biosimilar disclosures. “In the 6 years since the Forum was founded, we have found that while knowledge and perceptions of HCPs have increased…knowledge levels of patients are still low,” the group wrote.

Similarly, the drug company Bayer commented that the language of the study as it would be presented to participants sounded clinical and should be rewritten for consumer participants so that it was “patient friendly.”

The Hematology/Oncology Pharmacy Association asked that the study also evaluate the value of adding information about use of biosimilars for all indicated uses, or extrapolations, of the reference product. “Several studies have indicated that understanding, or lack of understanding of biosimilars in extrapolated indications, impacts a health care professional’s use of a biosimilar,” the group said.

A further critique of the study came from the Pharmaceutical Research and Manufacturers of America, which contended the study will not provide useful information because such information is already available to the FDA from other sources, the proposed study as designed is "flawed" because secondary end points are more important to a product’s indicated uses than the study design seems to suggest, and the study unfairly uses a genuine product, Humira (adalimumab) as a case example while using an anonymous or fictitious biosimilar.

That last point also drew an objection from AbbVie, which owns the Humira brand. The “FDA should refrain from using the name of a reference product currently on the market in the questionnaire and instead use a fictitious name for a reference product, as it does for the biosimilar,” the company said.

The importance of getting label language right for biosimilars is illustrated by the problem with consumers' understanding of alternative health products, the FDA noted. "

Research on consumer attitudes [has] found some people believe that FDA evaluates certain dietary supplement claims despite the presence and consumer awareness of language required by the Dietary Supplement Health and Education Act, which clearly states that FDA has not evaluated those claims."

Trade associations and companies in the biosimilars business ask the FDA to hone its proposed study on product disclosures.