The final 6 months of 2020 fueled many headlines of interest to the readership at The Center for Biosimilars®. For a summary of the most popular stories and related issues, read on.
A popular interview from The Center for Biosimilars® in July 2020 was with Byoungseo Choi, head of marketing for Celltrion Healthcare, a rising force in the world of biosimilar development. He discussed the company’s infliximab biosimilar (Inflectra, Remsima) and its value in the treatment of coronavirus disease 2019 (COVID-19). He also talked about Celltrion’s ambitious plans to launch multiple biosimilars over the next decade.
In 2020, visitors to The Center for Biosimilars® also paid close attention to stories about biosimilar launches by Cadila Pharmaceuticals of Ahmedabad, India. One such launch in July 2020 was a rituximab biosimilar (Ritucad) for the Indian market. A second Cadila launch the same month involved bevacizumab biosimilar Bevaro, for the treatment of ovarian cancer, glioblastoma multiforme, colorectal cancer, breast cancer, lung cancer, cervical cancer, and kidney cancer.
Although Alzumab (itolizumab) is not a biosimilar, the biosimilar developer Biocon Biologics attracted attention in 2020 when it announced that this anti-CD6 IgG1 monoclonal antibody had been approved for COVID-19–related illness by the Drugs Controller General of India. The drug was indicated for the emergency treatment of acute respiratory distress syndrome (ARDS) in patients with COVID-19. Biocon said the drug was of value in treating cytokine release syndrome, which is common among patients with moderate-to-severe ARDS. The drug is ordinarily used for treating chronic plaque psoriasis.
As pharmaceutical companies began to share promising news in the development of COVID-19–related treatments, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infection Diseases, stated in a town hall meeting that early-stage treatments such as monoclonal antibodies (mAbs) and direct-acting antivirals (DAAs) had contributed to impressive trial findings. At the time, the mAb infliximab (Remsima) was undergoing evaluation in the CATALYST study of COVID-19–related inflammation.
In addition to DAAs, which target specific virus proteins and disrupt viral replication and infection, convalescent plasma and hyperimmune globulin therapies, which involve the use of antibody-laden blood from patients who have recovered from COVID-19, also were candidates for potential use in the pandemic struggle, Fauci said.
The month of August 2020 saw Cadila put another biosimilar on the market in India, this time a teriparatide biosimilar (NuPTH), which is indicated for the treatment of osteoporosis and increased risk of bone fracture. The drug could be an important tool in providers’ armamentarium, Cadila said, calling India “the osteoporosis capital of the world.” The story attracted wide attention.
By this time in the pandemic, many biosimilar developers had joined the fight to find treatments for COVID-19. In some cases, biosimilars were under the microscope as candidates for effective management of the disease; in others, originator biologics became the focus, offering the potential for a role for biosimilars if the innovator products proved successful. In the latter group is Roche’s bevacizumab (Avastin), which was hypothesized to offer value in the treatment of pulmonary edema–related acute lung injury and ARDS. Pulmonary edema involves fluid buildup in the lungs, a condition that bevacizumab can suppress. The Center for Biosimilars® did a popular overview of these efforts to address the COVID-19 problem.
Related to this, Celltrion Healthcare’s mAb CT-P59 demonstrated positive results in the phase 1 CATALYST trial for management of COVID-19–related inflammation. Also, a commentary published in Lancet Rheumatology called for priority attention to developing anti–tumor necrosis factor (TNF) therapies for the treatment of COVID-19, saying that these agents, which include biosimilars, have been overlooked. “The potential of anti-TNF therapy as a treatment for COVID-19 is supported by both biological plausibility and observational clinical data,” the authors wrote. “Few current treatments under investigation have this level of supportive evidence.”
During the month of September, a published paper brought to prominence growing concerns among UK regulators about the relatively weak evidence provided by comparative biosimilar efficacy trials. Investigators have long contended that pharmacokinetic and pharmacodynamic studies can produce more exact comparative data to demonstrate biosimilar equivalency to reference products and that in-human efficacy trials lack a strong scientific basis for performing this task. With Brexit, the United Kingdom’s exit from the European Union, the country is assuming control for authorizing medicines, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency issued guidance stating that comparative efficacy/safety trials generally would not be necessary.
A well-read story in October 2020 concerned Amgen’s report on market share and pricing discounts achieved by biosimilars. Biosimilars introduce discounts to the market and capture share from originator products, but they also induce originator companies to drop their prices for reference products in order to maintain market share. The Amgen report demonstrated that both dynamics have been in play in recent years. Biosimilars, Amgen said, have been gaining traction, although it depends on the type of biosimilars and the length of time they have been available in the market.
Similarly, a report from IQVIA Institute for Human Data Science stated that concerns about limited biosimilar uptake in the United States appear to be overblown. “Some commonly held assumptions about patient and provider acceptance and comfort with biosimilars appear to be more conservative than data demonstrate,” said the authors of the report. They anticipated that drugs accounting for 51% of the spending on biologics would face biosimilar competition over the next 10 years.
The renewed concerns about the value of comparative clinical efficacy trials prompted Center for Biosimilars® Advisory Board Member Sarfaraz K. Niazi, PhD, to write a column about reasons why these trials add little to the weight of evidence for biosimilar approvals. “Comparative efficacy testing of biosimilars is redundant at best,” he wrote in this widely-read column.
Canadian provinces have made huge strides in establishing biosimilar use via mandatory switching. A November 2020 story about Alberta’s efforts in this regard saw high traffic from Center for Biosimilars® readers. Having begun its program in 2019, Alberta saw 16% of patients switched to biosimilars from use of 7 reference products, according to a presentation at the Terrapinn Festival of Biologics Basel 2020. The province is hoping to have 100% of patients switched by January 15, 2021. From the US standpoint, these are an enviable achievement and goal. British Columbia began a similar initiative 6 months earlier than Alberta and also has reported good results. Officials reported being able to funnel millions of dollars in savings back into medical programs to expand access for residents of the province. Other Canadian provinces reportedly are considering switching programs to achieve similar results. In August, biosimilars had an 8% usage share relative to reference drugs in Canada, vs rates of 50% to 95% for countries that have fully embraced these alternative biologics.
A well-read article in December concerned pegfilgrastim biosimilars, whose market share and use have seen some erosion due to the availability of on-body injectors (OBIs), which are marketed only for the originator brand, Neulasta. OBIs offer convenience but they are not 100% reliable, and providers and patients may prefer to use pegfilgrastim biosimilars instead, even though they require that patients return to the clinic for injections that the OBIs would perform automatically at the patient’s home. Studies presented at the American Society of Hematology Annual Meeting and Exposition demonstrated that the failure rate of OBIs adds to hospitalization costs. The savings from pegfilgrastim biosimilars, the authors argued, could significantly expand access to this medicine, which is used to reduce the incidence of febrile neutropenia in patients receiving chemotherapy.
During the month of December, Boehringer Ingelheim (BI) attracted attention with the filing of a citizen’s petition that asked the FDA to reconsider its interpretation of “strength of formulation” for biosimilars under the Public Health Service Act. The company wants the FDA to interpret strength to mean “total drug content” regardless of concentration or total volume. BI contends that originator companies that want to block biosimilars from challenging their market share may place undue stress on the FDA’s current interpretation of strength, which might delegitimize a biosimilar that is in fact equivalent to a reference product.
Finally, fresh guidance from the FDA on licensing procedures for biosimilars when it comes to interchangeability generated a large number of clicks from Center for Biosimilars® readers. The FDA asked applicants to be clear during the applications process whether they were seeking interchangeable status for their biosimilar candidates. The guidance was only in draft form and the FDA is accepting comments through January 19, 2021.