Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

Studies of trastuzumab biosimilars in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) have yielded significant findings, according to presentations at the 2020 San Antonio Breast Cancer Symposium.

Investigators achieved a 45.5% response rate in patients with HER2-positive mBC and 

 aberrations who were treated with the trastuzumab biosimilar Herzuma and an experimental PIK3CA pathway inhibitor (gedatolisib, PF-05212384) in a phase 2 pilot trial.

 pathway aberrations tend to promote tumor cell growth and survival despite treatment with monoclonal antibodies, chemotherapy, and radiotherapy. The study authors hypothesized the combination of trastuzuamb and gedatolisib would improve outcomes for select patients with disease progression who had exhausted approved treatment options for mBC.

They enrolled 15 patients with HER2-positive mBC with a known 

) and who had failed on multiple prior lines of therapy. Patients received a trastuzumab biosimilar 8 mg/kg intravenously for the first cycle and then 6 mg/kg every 3 weeks plus gedatolisib 180 mg on days 1, 8, and 15 every 21 days.

As of the data cutoff on August 4, 2020, 11 patients were eligible for response assessment. Five achieved partial response as their best response; 3, stable disease; and 3, progressive disease. All patients with partial response remain on the investigational treatment, with the longest term being 7.8 months. Among the patients with stable disease, 1 discontinued due to disease progression and 2 continue to receive therapy. The investigators said the disease control rate was 72.7% with no treatment-related fatal adverse events.

A multicenter, global, phase 3 study of the trastuzumab biosimilar MYL-1401O (Ogivri) in patients with HER2-positive mBC has demonstrated pharmacokinetic (PK) equivalence between the biosimilar and the reference product (Herceptin).

by the FDA in December 2017 and marketed in the United States December 2019.

Investigators randomized 485 patients 1:1 to receive the biosimilar or reference product, with the aim of assessing biosimilarity on the basis of efficacy, safety, population PK, and immunogenicity. They said 482 patients were included in the population PK analysis.

The measures for drug exposure at or near steady-state dosing were comparable for Ogivri and the reference drug, demonstrating PK biosimilarity, the investigators said. Steady state is the time the concentration of the drug in the body stays consistent during administration, with the amount of drug entering the patient’s system being equivalent to the rate of elimination.

Other measures of PKs also supported equivalence, they said. “Population PK profiles of [Ogivri] vs Herceptin were similar in patients with HER2-positive mBC. Model-based exposure measures were similar between treatments.”

They added that extracellular domain fragments of the HER2 receptor “were a strong determinant of trastuzumab clearance [elimination], and clearance was similar between [biosimilar and reference drug] treatments.” They observed that trough concentrations—drug concentrations immediately before the next dose—were similar between treatments at the end of cycle 1 and at cycle 6.

1. Kim JW, Ahn HK, Choi JG, et al. Phase II pilot study of trastuzumab biosimilar (Herzuma) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy [KM-10A/KCSG18-13 interim analysis]. Presented at: SABCS; December 8-11, 2020. Abstract PS11-39. www.sabcs.org/portals/sabcs2016/2020%20SABCS/Final%20PDF%20Docs%20111620_All%20PDF%20File%20No%20Embargoed%20Abstracts.pdf

2. Owen J, Rackley R, Liu M, et al. Population pharmacokinetics (pop PK) of MYL‑1401O (a trastuzumab biosimilar) and reference trastuzumab (Herceptin) in patients with HER2‑positive metastatic breast cancer (mBC). Presented at: SABCS; December 8-11, 2020. Abstract PS18-23. www.sabcs.org/portals/sabcs2016/2020%20SABCS/Final%20PDF%20Docs%20111620_All%20PDF%20File%20No%20Embargoed%20Abstracts.pdf

Articles

Two studies of trastuzumab biosimilars have improved understanding of these medicines as monotherapy and in combination with other agents in metastatic breast cancer.

Trastuzumab Biosimilar With PIK3CA Inhibitor Shows Efficacy in Advanced Breast Cancer

Shanghai Henlius Biotech said its adalimumab biosimilar candidate HLX03 has been 

by China’s National Medical Products Administration for the treatment of rheumatoid arthritis, ankylosing spondylitis, and plaque psoriasis.

This marks the third biosimilar that Henlius has developed and won approval for in China. The others are rituximab (HLX01) and trastuzumab (HLX02, Zercepac) biosimilars. Zercepac also has European marketing authorization.

Henlius said that it conducted numerous head-to-head trials of HLX03 and the adalimumab reference product (Humira), and that clinical, nonclinical, and analytical studies demonstrated HLX03 is highly similar to Humira. HLX03 will be commercialized in China by Wanbang Biopharma, a subsidiary of Fosun Pharma.

“The approval of this product marks the expansion of the company’s commercial pipeline into the field of autoimmune diseases, and the scope of patients that can benefit from Henlius products is further broadened,” Wenjie Zhang, CEO and president of Henlius, said.

positive phase 3 clinical study data for a bevacizumab biosimilar candidate (HLX04).

The approval of HLX03 marks the third biosimilar regulatory success in China for Henlius. 

Shanghai Henlius Biotech Gains China's Approval for Adalimumab Biosimilar

Investigators hope to improve durability of response in human epidermal growth factor receptor 2 (HER2)-positive solid tumors with a novel trastuzumab biosimilar conjugated to a toll-like receptor 7/8 agonist and designed to activate myeloid antigen presenting cells, which alert T cells to the presence of cancerous cells and mediate an immune response.

The investigational biosimilar (BDC-1001) holds potential as an improvement on anti-HER2 monoclonal antibodies in HER2-driven or -expressing cancers. In studies of mice with tumors resistant to conventional treatment, trastuzumab-based immune-stimulating antibody conjugates have elicited potent and durable antitumor efficacy “including complete tumor regression,” investigators said in an 

 presented at the 2020 San Antonio Breast Cancer Symposium.

“Importantly, BDC-1001 did not induce interstitial lung disease, cytokine release syndrome, or thrombocytopenia in primate studies," the investigators said.

The phase 1/2, first-in-human, dose-escalation and dose-expansion study will enroll up to 390 patients with HER2-expressing or HER2-amplified advanced solid tumors who have exhausted the potential for treatment with approved anti-HER2 treatments. Patients will receive BDC-1001 with or without an immune checkpoint inhibitor targeting PD-1.

The dose-escalation phase of the trial will help to determine safety and tolerability of the treatment and establish the phase 2 dose of BDC-1001 as monotherapy and in combination with an immune checkpoint inhibitor. Primary end points include incidence of adverse events, dose-limiting toxicities, and potential immune-related toxicities.

Patients will receive BDC-1001 intravenously every 3 weeks in increasing doses. The completion of the safety data portion of the trial will allow investigators to proceed with the immune checkpoint inhibitor combination component. The dose-expansion portion of the trial will evaluate both the monotherapy with BDC-1001 and the investigational agent in combination with a checkpoint inhibitor. The primary end point of the dose-expansion portion is overall response rate.

The investigators also hope to elucidate the mechanism of action for BDC-1001 and identify biomarkers to help improve selection of patients most likely to benefit from the treatment with and without checkpoint inhibitors.

Dumbrava EI, Sharma MR, Carvajal RD, et al. Phase 1/2 study of a novel HER2 targeting TLR7/8 immune-stimulating antibody conjugate (ISAC), BDC-1001, as a single agent and in combination with an immune checkpoint inhibitor in patients with advanced HER2-expressing solid tumors. Presented at: SABCS; December 8-11, 2020. Abstract OT-03-02. www.sabcs.org/portals/sabcs2016/2020%20SABCS/Final%20PDF%20Docs%20111620_All%20PDF%20File%20No%20Embargoed%20Abstracts.pdf

Investigators explained the potential for durable antitumor efficacy in patients with human epidermal growth factor receptor 2 (HER2)-expressing or -driven tumors who have exhausted other treatment options.

Biosimilar Conjugate Evaluated in HER2-Positive Patient Population

A single-center, retrospective data analysis in India evaluating safety and efficacy of biosimilar romiplostim (Romy) in patients with immune thrombocytopenic purpura (ITP) has demonstrated a high overall response rate (93%) without adverse events.

Romiplostim (Nplate) received US approval in 2008 for the treatment of ITP, which is characterized by an immune system attack on platelets that results in bruising, bleeding, and reddish-purple spots on the lower legs. The biosimilar Romy is 

Investigators enrolled 54 patients (male, 23; female, 31; median age, 40 years) with steroid-refractory or steroid-dependent ITP at the Haemato-Oncology Care Center in Vadodara, India, from July 2019 to January 2020. All patients had a pretreatment platelet count of less than 30,000/cmm. Romiplostim biosimilar was administered in a dose of 1 mcg/kg to 6 mcg/kg subcutaneously once a week.

Roughly 20% of patients (n = 12) had active bleeding and also received a concomitant rituximab 100 mg infusion once weekly for 4 weeks. For 51 patients, the overall response rate (ORR) with platelet count above 50,000 cmm; 4 patients (7%) had no response. Among patients who received rituximab with romiplostim, the ORR was 100% (12).

Investigators said the time to response was 1 week in 85% (46) of patients, and 16% (9) had a sustained response lasting more than 6 months even after discontinuing romiplostim at 4 weeks of therapy. They said 40% (21) had a sustained optimum response lasting more than 6 months with uninterrupted treatment. No patients experienced serious adverse events.

“Biosimilar romiplostim has shown rapid, excellent, and sustained response in the majority of ITP patients in our study,” said Seema S. Bhatwadekar, MD, MBBS, lead study author. “Its affordable cost [$160 per month] fulfills an unmet need for ITP patients requiring the best second line of treatment in India.”

Bhatwadekar SS, Deshpande SV, Khadse SV, et al. Efficacy and safety of biosimilar romiplostim in immune thrombocytopenic purpura: single centre retrospective data analysis. Presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020. Abstract 2676.

A high overall response rate of 93% was observed for patients with immune thrombocytopenic purpura who received romiplostim biosimilar. 

Romiplostim Biosimilar Study Demonstrates Safety, Efficacy in Real-World India Population

Anurag S. Rathore, PhD, has become the first from India to receive the Agilent Technologies Thought Leader Award. Rathore was 

for his contributions to biopharmaceutical research and his efforts to advance the molecular characterization of biosimilars.

The characterization of biosimilars is a process that helps determine the bioequivalence of these products to reference, or original, drugs. Characterization also establishes the nature and extent of differences between biosimilar candidates and their reference products and whether these are clinically meaningful.

As recipient of the award, Rathore receives Agilent equipment and a grant to support his research. He joins 47 

Agilent, a 1999 spinoff from Hewlett-Packard, is a Santa Clara, California–based analytical instrumentation developer and manufacturer. 

Rathore is a professor and scientist at the Indian Institute of Technology (IIT) Delhi. He earned his PhD from Yale University and currently works in the Department of Chemical Engineering at ITT Delhi. He is a member of the Parenteral Drug Association and American Chemical Society and is the author of more than 400 publications and presentations. He is also editor-in-chief of 

Preparative Biochemistry and Biotechnology

. Information about his publications can be accessed by clicking 

 about a study he conducted on reasons that applications for biosimilar regulatory approval fail.

Anurag S. Rathore, PhD, wins a grant and the use of scientific instruments from Agilent to further his investigation.

Rathore Wins Thought Leader Award for Biosimilar Characterization

Investigators said they were able to demonstrate the biosimilarity of a rituximab biosimilar (CT-P10 [Truxima]) to reference rituximab in a long-term (27 months) efficacy and safety study (N = 258) involving a single transition from the originator to the biosimilar in patients with low–tumor burden follicular lymphoma (LTBFL). CT-P10 is a Celltrion biosimilar that was approved by the FDA in November 2018 for patients with CD20-positive, B-cell non-Hodgkin lymphoma.

The trial was a randomized (1:1), controlled, double-blind, phase 3 study in LTBFL. Patients received CT-P10 (375 mg/m

) weekly or the reference product at the same dose for an induction period of 4 cycles, followed by maintenance treatment once every 2 months for 2 years. The primary end point was overall response rate (ORR) over 7 months, defined as the number of patients achieving complete response (CR), unconfirmed complete response, or partial response. The secondary end point was ORR during the study period, overall survival (OS), progression-free survival (PFS), and time to progression.

Most patients completed induction and initiated maintenance period 1 (CT-P10, n = 123; reference, n = 120). Reasons for treatment discontinuation were similar between treatment groups, with the most frequently reported reason in both groups being progressive disease.

Investigators reported no clinically meaningful differences in ORR or OS between treatment cohorts over the study period. The ORR was 88% (n = 115) in the CT-P10 cohort and 87% (n = 111) in the rituximab reference group. This included CR rates of 56% and 52% for the CT-P10 and rituximab reference groups, respectively.

Median PFS was not estimable in either group due to a low number of events. The investigators stressed caution in interpreting the significance of this “due to the relatively immature data set.” There was no difference in OS between groups, although median OS also was not estimable.

The investigators said 88% and 81% of patients in the CT-P10 and reference groups, respectively, experienced at least 1 treatment emergent adverse event, and 11% of patients in each group experienced treatment emergent serious adverse events. “There were no unexpected safety signals … after the single transition from rituximab [reference] to CT-P10,” said Larry W. Kwak, MD, PhD, lead author, City of Hope, Duarte, California.

“The overall similarity in ORR, OS, and safety over the study period supports the biosimilarity between the CT-P10 and rituximab [products]," Kwak said, adding that longer-term follow-up is needed to understand the efficacy findings.

Kwak LW, Sancho JM, Cho SG, et al. Long-term efficacy and safety (27 months) of the biosimilar CT-P10 in patients with low tumor burden follicular lymphoma. Presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020. Poster 1125. https://ash.confex.com/ash/2020/webprogram/Paper135999.html

A long-term, comparative, phase 3 trial of CT-P10 vs the rituximab originator product has provided evidence of biosimilar value in this blood disorder.

Celltrion's Rituximab Biosimilar Demonstrates Equivalence in Follicular Lymphoma

In a pair of simulation studies utilizing pegfilgrastim originator products and biosimilars, investigators set out to calculate the savings possible from switching to biosimilars and what could be achieved with those savings in terms of additional treatment. They found significant savings potential and concluded that hospitalization costs could be lowered by switching to biosimilar pegfilgrastim from the pegfilgrastim on-body injector (OBI).

The studies are due to be presented at the upcoming American Society of Hematology Annual Meeting and Exposition, December 5 to 8, 2020.

In one of the studies, investigators simulated the potential savings for a population of 20,000 patients with non-Hodgkin lymphoma.

 Based on average sales price (ASP) of the agents in question, they found that total savings of $371,444 were possible for the hypothetical patients if 10% were converted to pegfilgrastim biosimilar (Udenyca) from reference product or OBI and received 1 cycle of the prophylactic treatment (to prevent incidence of chemotherapy-induced febrile neutropenia). If 100% of patients were converted and received 6 cycles of treatment of the biosimilar, the potential savings climbed to $22.3 million.

Using a blended ASP, wholesale acquisition cost (WAC) basis, investigators said the potential savings in a single cycle of chemotherapy meant it was possible to expand access to Udenyca by 524 cycles at a 10% conversion rate and 5243 cycles at 100% conversion. They said 4 patients would have to be converted to purchase 1 additional cycle of biosimilar pegfilgrastim.

To pay for an additional cycle of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP), 8 patients would need to be converted from 1 cycle of reference pegfilgrastim to Udenyca, they said. This calculation was also based on the ASP/WAC blended rate. Investigators said expanded access to R-CHOP ranged from 282 cycles at 10% conversion to 2817 cycles at 100% conversion for patients who received a single cycle of chemotherapy. Over multiple cycles, the savings were potentially much higher.

“These simulation models demonstrate that significant cost savings for supportive cancer care can be generated through conversion,” they wrote.

In the second study, investigators found that pegfilgrastim biosimilar (Fulphila) used as prophylaxis for chemotherapy-induced febrile neutropenia has savings and access advantages over pegfilgrastim originator product delivered via the OBI, which is available only for the reference product.

The OBI has seen elevated usage during the coronavirus disease 2019 pandemic because it enables patients to receive doses outside the clinic, which is considered convenient and safe. However, investigators noted that the OBI has a failure rate of 1.7% to 6.9% that “predisposes patients to increased risk” of chemotherapy-related febrile neutropenia. These failures lead to hospitalizations. Cost savings generated from conversion to biosimilar pegfilgrastim (Fulphila) would create opportunities for expanded access, they wrote.

Investigators did a simulation analysis involving a cohort of 15,000 patients with diffuse large B-cell lymphoma at risk for febrile neutropenia. They said that after accounting for hospital costs related to OBI failure, the potential savings from the first cycle of prophylaxis at 10% conversion to the biosimilar were $406,118. This was based on an OBI failure rate of 1%. The savings climbed significantly based on additional cycles of treatment and higher assumed OBI failure rates. 

Investigators said the savings translated into expanded access of 118 additional cycles of Fulphila or 62 cycles of R-CHOP, also at 10% conversion with a 1% OBI failure rate.

Prophylaxis with Fulphila generated substantial cost savings compared with OBI ($379,230; 1 cycle of prophylaxis at 10% conversion), the investigators wrote. They concluded that biosimilar savings further increased when the costs of febrile neutropenia–related hospitalization from pegfilgrastim OBI failure were factored in.

1. McBride A, MacDonald K, Abraham I. Simulation modeling of cost-savings from conversion to biosimilar pegfilgrastim-cbqv for the prophylaxis of chemotherapy-induced neutropenia, and budget-neutral expanded access to prophylaxis and anti-neoplastic therapy from derived cost-savings in non-Hodgkin lymphoma. Presented at: 62nd ASH Annual Meeting and Exposition; December 5-8, 2020. Abstract 3425.

2. McBride A, MacDonald K, Abraham I. Conversion to biosimilar pegfilgrastim-jmdb from pegfilgrastim with on-body injector device in diffuse large B-cell lymphoma: simulation modeling of cost-savings and budget-neutral expanded access to prophylaxis and anti-neoplastic therapy considering device failure rate. Presented at: 62nd ASH Annual Meeting and Exposition; December 5-8, 2020. Abstract 3422.

The wearable injector has a failure rate that adds hospitalization costs; therefore, biosimilar pegfilgrastim may hold cost advantages, investigators conclude. 

Investigators: Biosimilar Pegfilgrastim Has Advantages Over Wearable Injector

For one company deeply involved in the production of biosimilars, expansion efforts are moving ahead where the company feels it is safest, given how well countries targeted for factory construction are managing coronavirus disease 2019 (COVID-19).

A little under 2 weeks ago, Celltrion announced that it would start building a $453.3 million biopharmaceutical factory in the Songdo district of Incheon, Republic of Korea, just southwest of Seoul, the capital city. Construction began on November 18, 2020, immediately following the announcement, and completion of the plant and a global research and development center are anticipated by May 2023. This construction is moving forward despite the pandemic.

of COVID-19 on November 29, according to the Korea Disease Control and Prevention Agency. Since the beginning of November, the country  has seen a resurgence of cases that has authorities now banning New Year celebrations and restricting other public gatherings.

Meanwhile, Celltrion continues to suspend construction activities related to its planned Wuhan factory site, where it announced early in 2020 the start of construction for a $514 million biologics plant, which would manufacture medicines for the Chinese market and perform contract manufacturing for other companies. That project didn’t get very far.

In January 2020, Celltrion withdrew its employees from Wuhan because of the pandemic and indicated it would monitor conditions before resuming activities. A spokesperson for Celltrion said this week that the Wuhan plans remain a reality, although the pandemic continues to be the reason for the construction suspension. “The Wuhan project is currently on hold because of the worldwide COVID-19 pandemic,” said Taegyun Kim.

At the time that Celltrion evacuated its employees from Wuhan, the city of 11 million was the global epicenter of the COVID-19 outbreak. The current, official infection rate and total number of cases in China are disputed owing to suspicions of significant underreporting. According to a tally of 

based on various official sources, the count was 18, far lower than in Republic of Korea. 

However, having a centralized system of epidemic response, contact tracing, a high respect for medical science, and s recent experience battling 

a serious contagion with high mortality (

, China was in an excellent position to combat COVID-19, according to a review article in 

. These factors support the notion that China has adopted a much more sophisticated and successful approach to managing COVID-19 than many other countries. Wuhan, in Hubei province, was originally placed under strict lockdown that lasted for 76 days. Public transport was halted, and checkpoints were established at transit centers. Family outdoor activities also were curtailed, and only 1 member of a family was allowed out to obtain needed supplies. Testing of 9 million citizens was completed within weeks, the article said.

Republic of Korea also has been held up as an example of successful COVID-19 response, although the resurgence there has prompted a tightening of restrictions.

Discretion may be the better part of valor for Celltrion, which, being based in Incheon, is much more familiar with conditions there than in China, although it ultimately wants to expand manufacturing operations in both markets. Celltrion has 2 existing manufacturing plants in Incheon, with capacity of 190,000 L of biomedicine production. The new plant under construction will add 60,000 L of capacity, with 8 bioreactors, for a total potential volume of 250,000 L, according to Kim. “The major purpose of the third plant will be to reinforce our multiproduct, small-size manufacturing capacity,” he said.

Three hours by plane to the southwest, the planned Wuhan manufacturing center would produce biopharmaceuticals for the Chinese domestic market and include a large-scale contract manufacturing facility for work with Celltrion’s clients, Kim said.

Both plants were envisioned in 2019 when Celltrion issued its “Vision 2030” blueprint for company expansion in the global biopharmaceuticals sector. The company anticipated spending 

 over the coming decade, during which it anticipated bringing at least 1 new biosimilar to market each year and challenging Pfizer for the lead position in the global pharmaceuticals industry. At the time, Celltrion had 3 biosimilars approved and marketed and intended to bring that number to 

, which would require expansion of biomedicine production capacity to 1 million L yearly. The Wuhan factory would have capacity for 120,000 L. Combined with the anticipated 250,000-L total in Republic of Korea, these factory projects would bring the company 37% of the way to the 1-million L goal. 

Republic of Korea is becoming a center of biologics manufacturing. Government information reported by the 

, or $874.5 million of the country’s $1.28 billion in biopharmaceutical exports in 2019, were biosimilars. The country’s biopharmaceutical market reached $2.17 billion last year, up 16.6% from the previous year, with annual growth clocking in at 10.2%. Not just Celltrion, but others also are racing to get ahead in the biopharmaceuticals market.

This past summer, Samsung Biologics, also a significant player in the biosimilar market, announced plans to build a fourth factory in Incheon, also in the Songdo district. This factory alone would have a capacity of 256,000 L, which Samsung said would be a global record for single-plant bioproduction capacity. The plant is intended to satisfy growing international demand for contract manufacturing. Although the factory announcement was made in August 2020, construction was scheduled to begin in September, with production expected to be partially compete by the end of 2022. 

The Celltrion spokesman said the Samsung Biologics project has not caused Celltrion to accelerate its plans. “Celltrion Group announced its future growth plan Vision 2030 in May 2019. The construction of the third plant and the global R&D center is part of this plan,” he said.

The Songdo district of Incheon, Republic of Korea, is rapidly becoming a major biopharmaceuticals production center. 

Celltrion Relies on Domestic Construction Amid the Pandemic

A merger of Pfizer’s Upjohn division and Mylan has brought a new member into the Biosimilars Forum, a trade association of biosimilar companies that advocates for greater biosimilar adoption.

The newly combined business entity, Viatris, has joined the original 9 members of the Washington, DC–based Biosimilars Forum. Viatris’ products from Pfizer include the erectile dysfunction aid Viagra (sildenafil) and cholesterol management drug Lipitor (atorvastatin); and from Mylan, Viatris gains the epinephrine auto-injector EpiPen.

On the US scene, Mylan has been an active partner with Biocon Biologics in the distribution of the trastuzumab (Ogivri) and pegfilgrastim (Fulphila) biosimilars. Mylan and Biocon had been working jointly to obtain interchangeable and biosimilar status for an insulin glargine product (Semglee), which obtained FDA approval in June 2020 and references Sanofi’s Lantus. At the time of the merger completion, Mylan had 20 biosimilars and insulin analogs in its portfolio, which included drugs under development. These included oncology, immunology, endocrinology, dermatology, and ophthalmology agents. Mylan was not previously a member of the Biosimilars Forum.

Upjohn had a marketing foothold in Asia and emerging markets, which was expected to complement Mylan’s focus on the United States and Europe. Pfizer’s biosimilars were not a part of the Upjohn spinoff. At the merger's announcement in July 2019, it was 

 that Viatris would develop biosimilars for abatacept (referencing Orencia, rheumatoid arthritis) and aflibercept (referencing Eylea, macular degeneration).

“Our biosimilars strategy continues to be focused on developing and executing on our long-term global franchise, focusing on market relevance and being a partner of choice to hospitals, clinics, pharmacies and physicia

said Tony Mauro, president of Developed Markets for Viatris. He previously served as chief commercial officer for Mylan.

 capable of $20 billion in worldwide revenues. The company is incorporated in Delaware and will have global centers in Pittsburgh, Pennsylvania; Shanghai, China; and Hyderabad, India.

Other members of the Biosimilars Forum are Biogen, Boehringer Ingelheim, Coherus BioSciences, Fresenius Kabi SwissBioSim, Merck and Co, Pfizer, Samsung Bioepis, Sandoz, and Teva.

The merger of Pfizer's Upjohn division and Mylan has created a biosimilars powerhouse with global reach. 

Newly Created Viatris Joins the Biosimilars Forum

 positive phase 3 clinical study data for its bevacizumab biosimilar candidate (HLX04). The trial compared the biosimilar with reference bevacizumab (Avastin) in combination with the chemotherapy regimens Xelox and mFolfox6 as a first-line treatment for metastatic colorectal cancer (mCRC).

Investigators said HLX04 demonstrated efficacy, safety, and immunogenicity equivalence to Avastin. Potential oncology indications for HLX04, besides colorectal cancer, include advanced, metastatic, or recurrent non–small cell lung cancer.

The trial, HLX04-mCRC03, was a multicenter, randomized, double-blind, parallel controlled study that randomized patients 1:1 to the biosimilar candidate (n = 338) or reference product (n = 337) delivered intravenously (7.5 mg/kg every 3 weeks when combined with XELOX or 5 mg/kg every 2 weeks when combined with mFOLFOX6). The primary end point was progression-free survival (PFS) at week 36.

PFS was 46.4% in the HLX04 group and 50.7% for the reference cohort. Henlius said the group difference was –4.2% and fell within predefined equivalence margins, demonstrating biosimilarity. Investigators said there was no statistically significant difference between the biosimilar candidate and reference drugs in terms of overall survival, PFS, objective response rate, time to response, or duration of response. Safety and immunogenicity profiles also were equivalent.

“The results of the phase 3 study demonstrated the equivalence in efficacy between HLX04 and reference bevacizumab with similar safety and immunogenicity profiles as first-line treatment for mCRC patients. HLX04 will provide an alternative treatment option for cancer patients as a potential biosimilar candidate,” the company said.

Henlius also aims to obtain indications for ophthalmic diseases such as wet age-related macular degeneration and diabetic retinopathy.

Biosimilar developer Celltrion Group said it has completed enrollment of 327 patients for a coronavirus disease 2019 (COVID-19) drug candidate phase 2 clinical trial. If results are positive, the company aims to apply for emergency use authorization from the Korean Ministry of Food and Drug Safety.

In preclinical studies, the agent, CT-P59, demonstrated a 100-fold 

 in viral load of SARS-CoV-2, the virus that causes COVID-19, as well as a reduction in lung inflammation.

The phase 2, randomized, double-blind, controlled trial is evaluating CT-P59 in patients with mild and moderate symptoms of COVID-19 in 3 cohorts: placebo, low concentration dose, and high concentration dose. “Results from the trial are expected in the coming weeks,” said Sang Joon Lee, senior executive vice president of Celltrion.

A Shanghai Henlius Biotech study demonstrates equivalence for its bevacizumab candidate, and Celltrion moves forward with a trial for a SARS-CoV-2 candidate. 