The year 2020 saw just 3 FDA approvals for biosimilars: Pfizer’s pegfilgrastim (Nyvepria) and Mylan/Fujifilm’s adalimumab (Hulio), in June and July, respectively, and Amgen’s rituximab (Riabni), in December. That was hardly a stellar rate of approvals, considering the 10 biosimilars approved in 2019; however, 2020 in biosimilars was eventful, nonetheless.
A review of the most popular stories published on The Center for Biosimilars® website shows the breadth of topics that captured readers’ attention. As the stories reveal, it was a year in which many events were shaped by the unfolding coronavirus 2019 pandemic (COVID-19). Despite this, biosimilars continued their upward march, capturing market share from reference products and gaining new regulatory support.
The year opened with the launch of Pfizer’s bevacizumab biosimilar Zirabev at a 23% discount to the wholesale acquisition cost of Avastin. This biosimilar was indicated for the treatment of metastatic colorectal cancer, recurrent or metastatic nonsquamous non–small cell lung cancer, recurrent glioblastoma, metastatic renal cell carcinoma, and persistent, recurrent, or metastatic cervical cancer.
Novo Nordisk launched “authorized” generic versions of its insulin products NovoLog and NovoLog mix at a 50% discount to its brand name reference products. The launch came prior to the March 23 transition under the Biologics Price Competition and Innovation Act (BPCIA), which was intended to create a new regulatory approval pathway for competitor insulin products that could break the dominance of originator brands.
The year later saw the launch of an insulin glargine contender (Semglee), by Biocon Biologics and Mylan, although this was approved under the 505(b)(2) New Drug Application pathway for generic medicines and was not technically a biosimilar. Analysts speculated that insulin biosimilars will start to appear in 2021 as a result of the BPCIA transition.
Merck announced that it would spin off its biosimilars business to focus on sales of its oncology drug pembrolizumab (Keytruda), a programmed cell death protein 1 (PD-1) inhibitor that thwarts cancer cells’ ability to switch off the immune system response. The biosimilars Merck sought to divest from included infliximab (Renflexis), trastuzumab (Ontruzant), and etanercept (Brenzys). Entrepreneurial forays into biosimilars may no longer hold interest for Merck, but the company is likely to see biosimilar competition for Keytruda in coming years. NeuClone of Sydney, Australia, announced in September 2020 it is developing biosimilar versions of the PD-1 inhibitors nivolumab (Opdivo) and pembrolizumab. These could start to reach market in 2027.
Pfizer also launched a trastuzumab biosimilar (Trazimera) for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. Other biosimilar versions of trastuzumab already were on the market. These included Ogivri (Mylan/Biocon Biologics) and Kanjinti (Amgen).
But more trastuzumab biosimilar launches were in store. Herzuma (Celltrion/Teva) and Ontruzant (Samsung Bioepis) were launched in March and April, respectively.
The arrival of COVID-19 in the early portion of the year was as disruptive for biosimilar development as for all other aspects of medical care. Clinical treatment programs—both patient visits and clinical trials—were delayed or cancelled. The FDA issued special guidance for the continuance of clinical studies to minimize the damage to data collection and medicinal product applications that COVID-19–related issues would cause.
One of the most-read Center for Biosimilars® stories during March was about the uncertainty COVID-19 injected into the drug supply chain. US pharmaceuticals were thought to be at risk for shortages owing to the country’s heavy reliance on internationally sourced materials. While these concerns were developing, the FDA announced that it would have to suspend on-site inspections of international facilities where drugs bound for the United States were manufactured.
Related to the COVID-19 crisis, pharmaceutical companies found themselves challenged to get the word out about their newer products, which encountered headwinds in the form of shifting priorities in the health care sector and struggles getting sales personnel into the field for product pitching. Quarantines made that difficult, if not impossible. A transition toward digital marketing that had begun previously was accelerated by these conditions.
Similarly, the FDA’s resources shifted toward managing hundreds of trials and reviews for COVID-19 vaccine candidates and related therapies, and agency officials restated throughout 2020 the singular focus required to get this job accomplished. For companies with product candidates considered less essential, it was possible that a delay in FDA consideration could be anticipated.
The pandemic forced Celltrion, of Incheon, Republic of Korea, to suspend construction of a $514 million biopharmaceutical manufacturing plant in Wuhan, the epicenter of the outbreak, but the company saw opportunity in the crisis and moved forward to develop therapeutic antibodies capable of neutralizing SARS-CoV-2, the virus responsible for COVID-19. The company reported encouraging results of development work and clinical trials throughout 2020, and in December, its COVID-19 antibody treatment CT-P59 was approved for patients with life-threatening conditions by the Republic of Korea Ministry of Food and Drug Safety, according to a Reuters report.
Among the leading biosimilar stories from May 2020 was a report about Celltrion’s efforts to gain European Union approval for its adalimumab biosimilar candidate CT-P17. The potential biosimilar was designed as a high-concentration formulation that Celltrion hoped would give it an edge against competitor products. In early December 2020, the company gained a positive recommendation for CT-P17 from the European Medicines Agency Committee for Medicinal Products for Human Use, and a final decision by the European Commission is anticipated in the early part of 2021. Adalimumab biosimilars in Europe have made progress against the reference product, Humira, but in the United States, the originator company, AbbVie, has managed to negotiate deals that will keep these biosimilars off the market until 2023.
Another newsmaker in May 2020 was the announcement that Gedeon Richter, of Hungary, would buy a tocilizimab biosimilar candidate (LusiNEX) from Mycenax, a pharmaceutical contract development and manufacturing organization in Taiwan. The biosimilar was thought to be useful in managing COVID-19–related pneumonia. Meanwhile, the reference product, Roche’s Actemra, received FDA approval for a phase 3 trial to evaluate safety and efficacy in adult patients hospitalized with pneumonia as a complication of COVID-19.
Biosimilar competition for Johnson & Johnson’s Stelara (ustekinumab) may be years off, and yet interleukin-23 (IL-23) inhibitors such as this are an important new class of drugs for the treatment of Crohn disease and ulcerative colitis. Other companies developing these products are AbbVie and Allergan, whose merger in 2020 was approved by the Federal Trade Commission, giving rise to concerns that this would limit competition in the IL-23 inhibitor market.
However, biosimilars are in development for IL-23 inhibitors. In 2020, NeuClone completed a phase 1 clinical trial for its ustekinumab biosimilar candidate NeuLara, and Formycon, of Martinsried-Planegg, Germany, is developing FYB202, another potential competitor for Stelara, which had global sales of $6.6 billion in 2019.
In June 2020, the World Health Organization (WHO) prequalified the rituximab biosimilar Truxima to provide a more affordable treatment option for blood cancers in lower-income countries. Riutuximab is used for the treatment of diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and follicular lymphoma. This was the second biosimilar prequalification for the WHO. In December 2020, the WHO prequalified its first biosimilar, a Samsung Bioepis trastuzumab biosimilar (Ontruzant).
Also this month, the FDA approved the Pfizer pegfilgrastim biosimilar Nyvepria, making this the fourth pegfilgrastim approved for use in the United States, with the others being Ziextenzo, Udenyca, and Fulphila. These products reference Amgen’s Neulasta. The FDA clearance brought Pfizer’s total approved biosimilars for the US market to 6. During the first half of 2020, Pfizer brought 2 biosimilars to market: the rituximab biosimilar Ruxience and Trazimera.